Bipolar Disorder

There’s a reason they’re called smartphones.

Indeed, how patients use their smartphones and where they take them provides insight into what has been termed their “digital phenotype.” It’s information that, analyzed correctly, becomes useful in differentiating bipolar disorder from borderline personality disorder, a distinction that’s often challenging in clinical practice, Kate E.A. Saunders, MD, DPhil, said at the virtual congress of the European College of Neuropsychopharmacology.

Dr. Saunders, a psychiatrist at the University of Oxford (England), and colleagues have developed a smartphone app enabling patients to briefly characterize their current mood on a daily basis, as well as a machine learning model to analyze this data stream as patients’ moods evolve over time. In their prospective longitudinal Automated Monitoring of Symptom Severity (AMoSS) study of 48 patients with a confirmed diagnosis of bipolar disorder, 31 with borderline personality disorder, and 51 healthy volunteers, the tool correctly classified 75% of participants into the correct diagnostic category on the basis of 20 daily mood ratings (Transl Psychiatry. 2018 Dec 13;81:274. doi: 10.1038/s41398-018-0334-0).

The app also monitors activity via accelerometry and geolocation to assess an individual’s circadian rest-activity patterns, as well as telephone use and texting behavior. In another report from AMoSS, Dr. Saunders and coinvestigators showed that these patterns also distinguish persons with bipolar disorder from those with borderline personality disorder, who in turn differ from healthy controls (Transl Psychiatry. 2019 Aug 20;91:195. doi: 10.1038/s41398-019-0526-2).

“I think we can use these approaches to inform our diagnostic practice. It doesn’t replace doctors, but clearly it can add to diagnostic accuracy,” she said.

Borderline personality disorder and bipolar disorder are common diagnoses with quite different treatment approaches and prognoses. Studies have shown that rates of misdiagnosis of the two disorders are significant. The challenge is that they share overlapping diagnostic criteria, including prominent mood instability, which is difficult to assess reliably in clinical practice. That’s because the assessment relies on retrospective self-report of how patients felt in the past, which is often colored by their present mood state. The smartphone app sidesteps that limitation by having patients rate their mood daily digitally across six categories – anxiety, elation, sadness, anger, irritability, and energy – on a 1-7 scale.

The machine learning model that analyzes this information organizes the voluminous data into what Dr. Saunders called “signatures of mood” and breaks them down using rough path theory, a mathematical concept based upon differential equations. Dr. Saunders and colleagues have demonstrated that the shifting daily mood self-rating patterns can be used not only to sharpen the differential diagnosis between bipolar disorder and borderline personality disorder, but also to predict future mood. Automated analysis of the past 20 previous mood self-ratings predicted the next day’s mood in healthy controls with 89%-98% accuracy, depending upon which of the six mood categories was under scrutiny.

The predictive power in patients with bipolar disorder was also good, ranging from 82% accuracy for the energetic and anxious domains to 90% for the angry mood category. This ability to predict future mood states could have clinical value by assisting bipolar patients in enhancing proactive self-management and managing their mood stability to avoid depressive or manic relapse, although this has yet to be studied.

“For borderline personality disorder the predictive accuracy was not so good – 70%-78% – but perhaps that doesn’t matter,” Dr. Saunders said. “Perhaps that difficulty in predicting mood may actually be quite a useful diagnostic marker.”

‘Mr. Jones, the doctor is ready to see your phone now.’

The app’s accelerometry and geolocation capabilities can also enhance diagnostic accuracy, as has been shown in the AMoSS study.

The geolocation analysis generates data on the places a patient has gone and how much time was spent there. Feeding that information into the machine learning model predicted the presence or absence of depression with 85% accuracy for bipolar disorder, but couldn’t predict depression at all in borderline personality disorder.

“So we get a sense that people with bipolar disorder have behavioral manifestations of their mood symptoms which are much more consistent with one another and appear to change very consistently with their mood state, whereas borderline personality disorder seems to be characterized by something that’s much more unstable and unpredictable – and we can pick up these predictive variables using our smartphones,” Dr. Saunders said.

As depressive symptoms arise in patients with bipolar disorder, affected individuals display much less day-to-day variability in movement as measured by accelerometry. These changes predicted bipolar disorder with 76% specificity and 48% sensitivity.

“That’s OK. But we can’t do that at all in people with borderline personality disorder, again highlighting the fact that behavioral manifestations and symptoms in these groups are very, very different,” Dr. Saunders observed.

In AMoSS, analysis of activity, geolocation, and distal temperature rhythms showed that the individuals with borderline personality disorder displayed evidence of delayed circadian function, with a distinctive rest-activity pattern that differed from persons with bipolar disorder. This delayed circadian function might provide a novel therapeutic target in borderline personality disorder, a condition for which there is a notable lack of effective pharmacologic and psychotherapeutic interventions.

Phone use patterns were revealing. Patients with bipolar disorder had an increased total telephone call frequency relative to the healthy controls, whereas those with borderline personality disorder used text messaging much more frequently, consistent with the notion that borderline patients have difficulty in interpersonal communication.

Smartphone-based diagnostic differentiation between bipolar disorder and borderline personality disorder isn’t ready for prime time use in clinical practice, Dr. Saunders said. This is groundbreaking work that needs to be refined and replicated in larger studies. There are important ethical and data protection issues that require attention. But patients are gung-ho. Dr. Saunders noted that participant compliance in AMoSS was “extraordinarily good,” at 82%. Moreover, even though the study lasted for 3 months, more than 60% of subjects continued filing mood reports for 12 months.

“Smartphones may also give us an improved understanding of the lived experience of people with mental health problems. That’s certainly the feedback we got a lot from patients. They enjoy using this technology. They feel it’s helpful to be able to show their clinician this is what it’s like for them,” Dr. Saunders said.
 

Clinical usefulness is limited

The study was interesting as a pilot, and it is technologically very innovative. However, at this stage, it is unclear how the results can be used clinically, said Igor Galynker, MD, PhD, when asked about the findings.

There is a place for using this type of technology for patients living in remote areas, for example. However, Dr. Galynker, director of the Richard and Cynthia Zirinsky Center for Bipolar Disorder in New York, said such technology should be viewed as augmentation rather than as a substitute for face-to-face treatment.

“Typically, if clinicians have enough time to speak to the patient and to take history, they can differentiate between bipolar disorder and borderline personality disorder: The former is cyclical, the latter is less so. However, this is hard to do without face-to-face contact, or when you only have 10 minutes,” said Dr. Galynker, professor of psychiatry at the Icahn School of Medicine and director of the Galynker Research and Prevention Laboratory, both at Mount Sinai in New York.

Dr. Saunders’ work is funded by the Wellcome Trust and the National Institute for Health Research. Dr. Galynker reported receiving funding from the National Institute of Mental Health and the American Foundation for Suicide Prevention. He has no other disclosures.

bjancin@mdedge.com

SOURCE: ECNP 2020. Session S21.

There’s a reason they’re called smartphones.

Indeed, how patients use their smartphones and where they take them provides insight into what has been termed their “digital phenotype.” It’s information that, analyzed correctly, becomes useful in differentiating bipolar disorder from borderline personality disorder, a distinction that’s often challenging in clinical practice, Kate E.A. Saunders, MD, DPhil, said at the virtual congress of the European College of Neuropsychopharmacology.

Dr. Saunders, a psychiatrist at the University of Oxford (England), and colleagues have developed a smartphone app enabling patients to briefly characterize their current mood on a daily basis, as well as a machine learning model to analyze this data stream as patients’ moods evolve over time. In their prospective longitudinal Automated Monitoring of Symptom Severity (AMoSS) study of 48 patients with a confirmed diagnosis of bipolar disorder, 31 with borderline personality disorder, and 51 healthy volunteers, the tool correctly classified 75% of participants into the correct diagnostic category on the basis of 20 daily mood ratings (Transl Psychiatry. 2018 Dec 13;81:274. doi: 10.1038/s41398-018-0334-0).

The app also monitors activity via accelerometry and geolocation to assess an individual’s circadian rest-activity patterns, as well as telephone use and texting behavior. In another report from AMoSS, Dr. Saunders and coinvestigators showed that these patterns also distinguish persons with bipolar disorder from those with borderline personality disorder, who in turn differ from healthy controls (Transl Psychiatry. 2019 Aug 20;91:195. doi: 10.1038/s41398-019-0526-2).

“I think we can use these approaches to inform our diagnostic practice. It doesn’t replace doctors, but clearly it can add to diagnostic accuracy,” she said.

Borderline personality disorder and bipolar disorder are common diagnoses with quite different treatment approaches and prognoses. Studies have shown that rates of misdiagnosis of the two disorders are significant. The challenge is that they share overlapping diagnostic criteria, including prominent mood instability, which is difficult to assess reliably in clinical practice. That’s because the assessment relies on retrospective self-report of how patients felt in the past, which is often colored by their present mood state. The smartphone app sidesteps that limitation by having patients rate their mood daily digitally across six categories – anxiety, elation, sadness, anger, irritability, and energy – on a 1-7 scale.

The machine learning model that analyzes this information organizes the voluminous data into what Dr. Saunders called “signatures of mood” and breaks them down using rough path theory, a mathematical concept based upon differential equations. Dr. Saunders and colleagues have demonstrated that the shifting daily mood self-rating patterns can be used not only to sharpen the differential diagnosis between bipolar disorder and borderline personality disorder, but also to predict future mood. Automated analysis of the past 20 previous mood self-ratings predicted the next day’s mood in healthy controls with 89%-98% accuracy, depending upon which of the six mood categories was under scrutiny.

The predictive power in patients with bipolar disorder was also good, ranging from 82% accuracy for the energetic and anxious domains to 90% for the angry mood category. This ability to predict future mood states could have clinical value by assisting bipolar patients in enhancing proactive self-management and managing their mood stability to avoid depressive or manic relapse, although this has yet to be studied.

“For borderline personality disorder the predictive accuracy was not so good – 70%-78% – but perhaps that doesn’t matter,” Dr. Saunders said. “Perhaps that difficulty in predicting mood may actually be quite a useful diagnostic marker.”

‘Mr. Jones, the doctor is ready to see your phone now.’

The app’s accelerometry and geolocation capabilities can also enhance diagnostic accuracy, as has been shown in the AMoSS study.

The geolocation analysis generates data on the places a patient has gone and how much time was spent there. Feeding that information into the machine learning model predicted the presence or absence of depression with 85% accuracy for bipolar disorder, but couldn’t predict depression at all in borderline personality disorder.

“So we get a sense that people with bipolar disorder have behavioral manifestations of their mood symptoms which are much more consistent with one another and appear to change very consistently with their mood state, whereas borderline personality disorder seems to be characterized by something that’s much more unstable and unpredictable – and we can pick up these predictive variables using our smartphones,” Dr. Saunders said.

As depressive symptoms arise in patients with bipolar disorder, affected individuals display much less day-to-day variability in movement as measured by accelerometry. These changes predicted bipolar disorder with 76% specificity and 48% sensitivity.

“That’s OK. But we can’t do that at all in people with borderline personality disorder, again highlighting the fact that behavioral manifestations and symptoms in these groups are very, very different,” Dr. Saunders observed.

In AMoSS, analysis of activity, geolocation, and distal temperature rhythms showed that the individuals with borderline personality disorder displayed evidence of delayed circadian function, with a distinctive rest-activity pattern that differed from persons with bipolar disorder. This delayed circadian function might provide a novel therapeutic target in borderline personality disorder, a condition for which there is a notable lack of effective pharmacologic and psychotherapeutic interventions.

Phone use patterns were revealing. Patients with bipolar disorder had an increased total telephone call frequency relative to the healthy controls, whereas those with borderline personality disorder used text messaging much more frequently, consistent with the notion that borderline patients have difficulty in interpersonal communication.

Smartphone-based diagnostic differentiation between bipolar disorder and borderline personality disorder isn’t ready for prime time use in clinical practice, Dr. Saunders said. This is groundbreaking work that needs to be refined and replicated in larger studies. There are important ethical and data protection issues that require attention. But patients are gung-ho. Dr. Saunders noted that participant compliance in AMoSS was “extraordinarily good,” at 82%. Moreover, even though the study lasted for 3 months, more than 60% of subjects continued filing mood reports for 12 months.

“Smartphones may also give us an improved understanding of the lived experience of people with mental health problems. That’s certainly the feedback we got a lot from patients. They enjoy using this technology. They feel it’s helpful to be able to show their clinician this is what it’s like for them,” Dr. Saunders said.
 

Clinical usefulness is limited

The study was interesting as a pilot, and it is technologically very innovative. However, at this stage, it is unclear how the results can be used clinically, said Igor Galynker, MD, PhD, when asked about the findings.

There is a place for using this type of technology for patients living in remote areas, for example. However, Dr. Galynker, director of the Richard and Cynthia Zirinsky Center for Bipolar Disorder in New York, said such technology should be viewed as augmentation rather than as a substitute for face-to-face treatment.

“Typically, if clinicians have enough time to speak to the patient and to take history, they can differentiate between bipolar disorder and borderline personality disorder: The former is cyclical, the latter is less so. However, this is hard to do without face-to-face contact, or when you only have 10 minutes,” said Dr. Galynker, professor of psychiatry at the Icahn School of Medicine and director of the Galynker Research and Prevention Laboratory, both at Mount Sinai in New York.

Dr. Saunders’ work is funded by the Wellcome Trust and the National Institute for Health Research. Dr. Galynker reported receiving funding from the National Institute of Mental Health and the American Foundation for Suicide Prevention. He has no other disclosures.

bjancin@mdedge.com

SOURCE: ECNP 2020. Session S21.

There’s a reason they’re called smartphones.

Indeed, how patients use their smartphones and where they take them provides insight into what has been termed their “digital phenotype.” It’s information that, analyzed correctly, becomes useful in differentiating bipolar disorder from borderline personality disorder, a distinction that’s often challenging in clinical practice, Kate E.A. Saunders, MD, DPhil, said at the virtual congress of the European College of Neuropsychopharmacology.

Dr. Saunders, a psychiatrist at the University of Oxford (England), and colleagues have developed a smartphone app enabling patients to briefly characterize their current mood on a daily basis, as well as a machine learning model to analyze this data stream as patients’ moods evolve over time. In their prospective longitudinal Automated Monitoring of Symptom Severity (AMoSS) study of 48 patients with a confirmed diagnosis of bipolar disorder, 31 with borderline personality disorder, and 51 healthy volunteers, the tool correctly classified 75% of participants into the correct diagnostic category on the basis of 20 daily mood ratings (Transl Psychiatry. 2018 Dec 13;81:274. doi: 10.1038/s41398-018-0334-0).

The app also monitors activity via accelerometry and geolocation to assess an individual’s circadian rest-activity patterns, as well as telephone use and texting behavior. In another report from AMoSS, Dr. Saunders and coinvestigators showed that these patterns also distinguish persons with bipolar disorder from those with borderline personality disorder, who in turn differ from healthy controls (Transl Psychiatry. 2019 Aug 20;91:195. doi: 10.1038/s41398-019-0526-2).

“I think we can use these approaches to inform our diagnostic practice. It doesn’t replace doctors, but clearly it can add to diagnostic accuracy,” she said.

Borderline personality disorder and bipolar disorder are common diagnoses with quite different treatment approaches and prognoses. Studies have shown that rates of misdiagnosis of the two disorders are significant. The challenge is that they share overlapping diagnostic criteria, including prominent mood instability, which is difficult to assess reliably in clinical practice. That’s because the assessment relies on retrospective self-report of how patients felt in the past, which is often colored by their present mood state. The smartphone app sidesteps that limitation by having patients rate their mood daily digitally across six categories – anxiety, elation, sadness, anger, irritability, and energy – on a 1-7 scale.

The machine learning model that analyzes this information organizes the voluminous data into what Dr. Saunders called “signatures of mood” and breaks them down using rough path theory, a mathematical concept based upon differential equations. Dr. Saunders and colleagues have demonstrated that the shifting daily mood self-rating patterns can be used not only to sharpen the differential diagnosis between bipolar disorder and borderline personality disorder, but also to predict future mood. Automated analysis of the past 20 previous mood self-ratings predicted the next day’s mood in healthy controls with 89%-98% accuracy, depending upon which of the six mood categories was under scrutiny.

The predictive power in patients with bipolar disorder was also good, ranging from 82% accuracy for the energetic and anxious domains to 90% for the angry mood category. This ability to predict future mood states could have clinical value by assisting bipolar patients in enhancing proactive self-management and managing their mood stability to avoid depressive or manic relapse, although this has yet to be studied.

“For borderline personality disorder the predictive accuracy was not so good – 70%-78% – but perhaps that doesn’t matter,” Dr. Saunders said. “Perhaps that difficulty in predicting mood may actually be quite a useful diagnostic marker.”

‘Mr. Jones, the doctor is ready to see your phone now.’

The app’s accelerometry and geolocation capabilities can also enhance diagnostic accuracy, as has been shown in the AMoSS study.

The geolocation analysis generates data on the places a patient has gone and how much time was spent there. Feeding that information into the machine learning model predicted the presence or absence of depression with 85% accuracy for bipolar disorder, but couldn’t predict depression at all in borderline personality disorder.

“So we get a sense that people with bipolar disorder have behavioral manifestations of their mood symptoms which are much more consistent with one another and appear to change very consistently with their mood state, whereas borderline personality disorder seems to be characterized by something that’s much more unstable and unpredictable – and we can pick up these predictive variables using our smartphones,” Dr. Saunders said.

As depressive symptoms arise in patients with bipolar disorder, affected individuals display much less day-to-day variability in movement as measured by accelerometry. These changes predicted bipolar disorder with 76% specificity and 48% sensitivity.

“That’s OK. But we can’t do that at all in people with borderline personality disorder, again highlighting the fact that behavioral manifestations and symptoms in these groups are very, very different,” Dr. Saunders observed.

In AMoSS, analysis of activity, geolocation, and distal temperature rhythms showed that the individuals with borderline personality disorder displayed evidence of delayed circadian function, with a distinctive rest-activity pattern that differed from persons with bipolar disorder. This delayed circadian function might provide a novel therapeutic target in borderline personality disorder, a condition for which there is a notable lack of effective pharmacologic and psychotherapeutic interventions.

Phone use patterns were revealing. Patients with bipolar disorder had an increased total telephone call frequency relative to the healthy controls, whereas those with borderline personality disorder used text messaging much more frequently, consistent with the notion that borderline patients have difficulty in interpersonal communication.

Smartphone-based diagnostic differentiation between bipolar disorder and borderline personality disorder isn’t ready for prime time use in clinical practice, Dr. Saunders said. This is groundbreaking work that needs to be refined and replicated in larger studies. There are important ethical and data protection issues that require attention. But patients are gung-ho. Dr. Saunders noted that participant compliance in AMoSS was “extraordinarily good,” at 82%. Moreover, even though the study lasted for 3 months, more than 60% of subjects continued filing mood reports for 12 months.

“Smartphones may also give us an improved understanding of the lived experience of people with mental health problems. That’s certainly the feedback we got a lot from patients. They enjoy using this technology. They feel it’s helpful to be able to show their clinician this is what it’s like for them,” Dr. Saunders said.
 

Clinical usefulness is limited

The study was interesting as a pilot, and it is technologically very innovative. However, at this stage, it is unclear how the results can be used clinically, said Igor Galynker, MD, PhD, when asked about the findings.

There is a place for using this type of technology for patients living in remote areas, for example. However, Dr. Galynker, director of the Richard and Cynthia Zirinsky Center for Bipolar Disorder in New York, said such technology should be viewed as augmentation rather than as a substitute for face-to-face treatment.

“Typically, if clinicians have enough time to speak to the patient and to take history, they can differentiate between bipolar disorder and borderline personality disorder: The former is cyclical, the latter is less so. However, this is hard to do without face-to-face contact, or when you only have 10 minutes,” said Dr. Galynker, professor of psychiatry at the Icahn School of Medicine and director of the Galynker Research and Prevention Laboratory, both at Mount Sinai in New York.

Dr. Saunders’ work is funded by the Wellcome Trust and the National Institute for Health Research. Dr. Galynker reported receiving funding from the National Institute of Mental Health and the American Foundation for Suicide Prevention. He has no other disclosures.

bjancin@mdedge.com

SOURCE: ECNP 2020. Session S21.

When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.

“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”

Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.

Bipolar disorder with associated psychosis

In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.

“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”

Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.

Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”

In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.

Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.

In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
 

Bipolar disorder with anxiety

An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.

In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.

“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”

To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. Olanzapine can also be potentially used in cases where a patient has mania and anxiety to treat both conditions, he added.

Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
 

Bipolar disorder and ADHD

Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.

“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.

Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.

“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.

Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.

In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).

Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).

“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.

He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.

When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.

“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”

Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.

Bipolar disorder with associated psychosis

In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.

“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”

Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.

Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”

In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.

Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.

In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
 

Bipolar disorder with anxiety

An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.

In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.

“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”

To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. Olanzapine can also be potentially used in cases where a patient has mania and anxiety to treat both conditions, he added.

Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
 

Bipolar disorder and ADHD

Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.

“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.

Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.

“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.

Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.

In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).

Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).

“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.

He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.

When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.

“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”

Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.

Bipolar disorder with associated psychosis

In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.

“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”

Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.

Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”

In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.

Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.

In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
 

Bipolar disorder with anxiety

An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.

In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.

“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”

To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. Olanzapine can also be potentially used in cases where a patient has mania and anxiety to treat both conditions, he added.

Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
 

Bipolar disorder and ADHD

Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.

“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.

Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.

“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.

Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.

In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).

Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).

“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.

He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.

Adding psychotherapy to pharmacotherapy benefits patients with bipolar disorder (BD), particularly when delivered in family or group settings, results of a new meta-analysis confirms.

Outpatients with BD receiving drug therapy “should also be offered psychosocial treatments that emphasize illness management strategies and enhance coping skills; delivering these components in family or group format may be especially advantageous,” wrote the investigators, led by David Miklowitz, PhD, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior.

The study was published online Oct. 14 in JAMA Psychiatry.
 

Drugs alone not enough

It’s increasingly recognized that drug therapy alone can’t prevent recurrences of BD or fully alleviate postepisode symptoms or functional impairment, the researchers noted in their article. Several psychotherapy protocols have been shown to benefit patients with BD when used in conjunction with drug therapy, but little is known about their comparative effectiveness.

To investigate, the researchers conducted a systematic review and component network meta-analysis of 39 randomized clinical trials (36 involving adults and three involving adolescents).

The trials involved 3,863 patients with BD and compared pharmacotherapy used in conjunction with manualized psychotherapy (cognitive-behavioral therapy [CBT], family or conjoint therapy, interpersonal therapy, and/or psychoeducational therapy) with pharmacotherapy delivered in conjunction with a control intervention (supportive therapy or treatment as usual).

Across 20 two-group trials that provided usable information, manualized psychotherapies were associated with a lower probability of illness recurrence (the primary outcome), compared with control interventions (odds ratio, 0.56; 95% CI, 0.43-0.74).

Psychoeducation with guided practice of illness management skills in a family or group format was superior to these strategies delivered in an individual format (OR, 0.12; 95% CI, 0.02-0.94).

Family or conjoint therapy and brief psychoeducation were associated with lower attrition rates than standard psychoeducation.

For the secondary outcome of stabilization of depressive or manic symptoms over 12 months, CBT and, with less certainty, family or conjoint therapy and interpersonal therapy were more effective than treatment as usual.

The investigators note that the findings are in line with a network meta-analysis published earlier this year that found that combining psychotherapy with pharmacotherapy is the best option for stabilizing episodes and preventing recurrences of major depression.

“[T]here is enough evidence from this analysis and others to conclude that health care systems should offer combinations of evidence-based pharmacotherapy and psychotherapy” to outpatients with BD, the researchers note.

“When the goals center on prevention of recurrences, patients should be engaged in family or group psychoeducation with guided skills training and active tasks to enhance coping skills (e.g., monitoring and managing prodromal symptoms) rather than being passive recipients of didactic education,” they wrote.

“When the immediate goal is recovery from moderately severe depressive or manic symptoms, cognitive restructuring, regulating daily rhythms, and communication training may be associated with stabilization,” they added.
 

A call to action

The coauthors of an editorial in JAMA Psychiatry noted that the findings “further reinforce extant treatment guidelines recommending medication management and adjunctive evidence-based psychosocial treatments for individuals with BD.”

The findings also “identify specific treatment components and formats most strongly associated with preventing relapse and addressing mood symptoms,” write Tina Goldstein, PhD, and Danella Hafeman, MD, PhD, from Western Psychiatric Hospital, University of Pittsburgh.

The study “may further serve as a call to action to enhance availability and uptake of these treatments in the community. Unfortunately, data suggest substantially lower rates of psychotherapy receipt (26%-50%), compared with medication management (46%-90%) among adults with BD,” they wrote.

Dr. Goldstein and Dr. Hafeman noted future steps for the field include “demonstrating effectiveness of evidence-based treatment approaches for BD in the community, maximizing accessibility, and furthering knowledge that informs individualized treatment selection with substantial promise to optimize outcomes for individuals with BD.”

The study was supported in part by a grant from the National Institute for Health Research Oxford Health Biomedical Research Centre. Dr. Miklowitz has received research support from the NIHR, the Danny Alberts Foundation, the Attias Family Foundation, the Carl and Roberta Deutsch Foundation, the Kayne Family Foundation, AIM for Mental Health, and the Max Gray Fund; book royalties from Guilford Press and John Wiley and Sons; and served as principal investigator on four of the trials included in this meta-analysis. Dr. Goldstein has received grants from the National Institute of Mental Health, the American Foundation for Suicide Prevention, the University of Pittsburgh Clinical and Translational Science Institute, and the Brain and Behavior Research Foundation and royalties from Guilford Press outside the submitted work. Dr. Hafeman has received grants from the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Klingenstein Third Generation Foundation.

This article first appeared on Medscape.com.

Adding psychotherapy to pharmacotherapy benefits patients with bipolar disorder (BD), particularly when delivered in family or group settings, results of a new meta-analysis confirms.

Outpatients with BD receiving drug therapy “should also be offered psychosocial treatments that emphasize illness management strategies and enhance coping skills; delivering these components in family or group format may be especially advantageous,” wrote the investigators, led by David Miklowitz, PhD, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior.

The study was published online Oct. 14 in JAMA Psychiatry.
 

Drugs alone not enough

It’s increasingly recognized that drug therapy alone can’t prevent recurrences of BD or fully alleviate postepisode symptoms or functional impairment, the researchers noted in their article. Several psychotherapy protocols have been shown to benefit patients with BD when used in conjunction with drug therapy, but little is known about their comparative effectiveness.

To investigate, the researchers conducted a systematic review and component network meta-analysis of 39 randomized clinical trials (36 involving adults and three involving adolescents).

The trials involved 3,863 patients with BD and compared pharmacotherapy used in conjunction with manualized psychotherapy (cognitive-behavioral therapy [CBT], family or conjoint therapy, interpersonal therapy, and/or psychoeducational therapy) with pharmacotherapy delivered in conjunction with a control intervention (supportive therapy or treatment as usual).

Across 20 two-group trials that provided usable information, manualized psychotherapies were associated with a lower probability of illness recurrence (the primary outcome), compared with control interventions (odds ratio, 0.56; 95% CI, 0.43-0.74).

Psychoeducation with guided practice of illness management skills in a family or group format was superior to these strategies delivered in an individual format (OR, 0.12; 95% CI, 0.02-0.94).

Family or conjoint therapy and brief psychoeducation were associated with lower attrition rates than standard psychoeducation.

For the secondary outcome of stabilization of depressive or manic symptoms over 12 months, CBT and, with less certainty, family or conjoint therapy and interpersonal therapy were more effective than treatment as usual.

The investigators note that the findings are in line with a network meta-analysis published earlier this year that found that combining psychotherapy with pharmacotherapy is the best option for stabilizing episodes and preventing recurrences of major depression.

“[T]here is enough evidence from this analysis and others to conclude that health care systems should offer combinations of evidence-based pharmacotherapy and psychotherapy” to outpatients with BD, the researchers note.

“When the goals center on prevention of recurrences, patients should be engaged in family or group psychoeducation with guided skills training and active tasks to enhance coping skills (e.g., monitoring and managing prodromal symptoms) rather than being passive recipients of didactic education,” they wrote.

“When the immediate goal is recovery from moderately severe depressive or manic symptoms, cognitive restructuring, regulating daily rhythms, and communication training may be associated with stabilization,” they added.
 

A call to action

The coauthors of an editorial in JAMA Psychiatry noted that the findings “further reinforce extant treatment guidelines recommending medication management and adjunctive evidence-based psychosocial treatments for individuals with BD.”

The findings also “identify specific treatment components and formats most strongly associated with preventing relapse and addressing mood symptoms,” write Tina Goldstein, PhD, and Danella Hafeman, MD, PhD, from Western Psychiatric Hospital, University of Pittsburgh.

The study “may further serve as a call to action to enhance availability and uptake of these treatments in the community. Unfortunately, data suggest substantially lower rates of psychotherapy receipt (26%-50%), compared with medication management (46%-90%) among adults with BD,” they wrote.

Dr. Goldstein and Dr. Hafeman noted future steps for the field include “demonstrating effectiveness of evidence-based treatment approaches for BD in the community, maximizing accessibility, and furthering knowledge that informs individualized treatment selection with substantial promise to optimize outcomes for individuals with BD.”

The study was supported in part by a grant from the National Institute for Health Research Oxford Health Biomedical Research Centre. Dr. Miklowitz has received research support from the NIHR, the Danny Alberts Foundation, the Attias Family Foundation, the Carl and Roberta Deutsch Foundation, the Kayne Family Foundation, AIM for Mental Health, and the Max Gray Fund; book royalties from Guilford Press and John Wiley and Sons; and served as principal investigator on four of the trials included in this meta-analysis. Dr. Goldstein has received grants from the National Institute of Mental Health, the American Foundation for Suicide Prevention, the University of Pittsburgh Clinical and Translational Science Institute, and the Brain and Behavior Research Foundation and royalties from Guilford Press outside the submitted work. Dr. Hafeman has received grants from the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Klingenstein Third Generation Foundation.

This article first appeared on Medscape.com.

Adding psychotherapy to pharmacotherapy benefits patients with bipolar disorder (BD), particularly when delivered in family or group settings, results of a new meta-analysis confirms.

Outpatients with BD receiving drug therapy “should also be offered psychosocial treatments that emphasize illness management strategies and enhance coping skills; delivering these components in family or group format may be especially advantageous,” wrote the investigators, led by David Miklowitz, PhD, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior.

The study was published online Oct. 14 in JAMA Psychiatry.
 

Drugs alone not enough

It’s increasingly recognized that drug therapy alone can’t prevent recurrences of BD or fully alleviate postepisode symptoms or functional impairment, the researchers noted in their article. Several psychotherapy protocols have been shown to benefit patients with BD when used in conjunction with drug therapy, but little is known about their comparative effectiveness.

To investigate, the researchers conducted a systematic review and component network meta-analysis of 39 randomized clinical trials (36 involving adults and three involving adolescents).

The trials involved 3,863 patients with BD and compared pharmacotherapy used in conjunction with manualized psychotherapy (cognitive-behavioral therapy [CBT], family or conjoint therapy, interpersonal therapy, and/or psychoeducational therapy) with pharmacotherapy delivered in conjunction with a control intervention (supportive therapy or treatment as usual).

Across 20 two-group trials that provided usable information, manualized psychotherapies were associated with a lower probability of illness recurrence (the primary outcome), compared with control interventions (odds ratio, 0.56; 95% CI, 0.43-0.74).

Psychoeducation with guided practice of illness management skills in a family or group format was superior to these strategies delivered in an individual format (OR, 0.12; 95% CI, 0.02-0.94).

Family or conjoint therapy and brief psychoeducation were associated with lower attrition rates than standard psychoeducation.

For the secondary outcome of stabilization of depressive or manic symptoms over 12 months, CBT and, with less certainty, family or conjoint therapy and interpersonal therapy were more effective than treatment as usual.

The investigators note that the findings are in line with a network meta-analysis published earlier this year that found that combining psychotherapy with pharmacotherapy is the best option for stabilizing episodes and preventing recurrences of major depression.

“[T]here is enough evidence from this analysis and others to conclude that health care systems should offer combinations of evidence-based pharmacotherapy and psychotherapy” to outpatients with BD, the researchers note.

“When the goals center on prevention of recurrences, patients should be engaged in family or group psychoeducation with guided skills training and active tasks to enhance coping skills (e.g., monitoring and managing prodromal symptoms) rather than being passive recipients of didactic education,” they wrote.

“When the immediate goal is recovery from moderately severe depressive or manic symptoms, cognitive restructuring, regulating daily rhythms, and communication training may be associated with stabilization,” they added.
 

A call to action

The coauthors of an editorial in JAMA Psychiatry noted that the findings “further reinforce extant treatment guidelines recommending medication management and adjunctive evidence-based psychosocial treatments for individuals with BD.”

The findings also “identify specific treatment components and formats most strongly associated with preventing relapse and addressing mood symptoms,” write Tina Goldstein, PhD, and Danella Hafeman, MD, PhD, from Western Psychiatric Hospital, University of Pittsburgh.

The study “may further serve as a call to action to enhance availability and uptake of these treatments in the community. Unfortunately, data suggest substantially lower rates of psychotherapy receipt (26%-50%), compared with medication management (46%-90%) among adults with BD,” they wrote.

Dr. Goldstein and Dr. Hafeman noted future steps for the field include “demonstrating effectiveness of evidence-based treatment approaches for BD in the community, maximizing accessibility, and furthering knowledge that informs individualized treatment selection with substantial promise to optimize outcomes for individuals with BD.”

The study was supported in part by a grant from the National Institute for Health Research Oxford Health Biomedical Research Centre. Dr. Miklowitz has received research support from the NIHR, the Danny Alberts Foundation, the Attias Family Foundation, the Carl and Roberta Deutsch Foundation, the Kayne Family Foundation, AIM for Mental Health, and the Max Gray Fund; book royalties from Guilford Press and John Wiley and Sons; and served as principal investigator on four of the trials included in this meta-analysis. Dr. Goldstein has received grants from the National Institute of Mental Health, the American Foundation for Suicide Prevention, the University of Pittsburgh Clinical and Translational Science Institute, and the Brain and Behavior Research Foundation and royalties from Guilford Press outside the submitted work. Dr. Hafeman has received grants from the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Klingenstein Third Generation Foundation.

This article first appeared on Medscape.com.

One of the hottest topics now in psychiatry is the possibility of repurposing long-established cardiovascular medications for treatment of patients with serious mental illness, Livia De Picker, MD, PhD, said at the virtual congress of the European College of Neuropsychopharmacology.

Courtesy Dr. Livia De Picker

The appeal is multifold. A huge unmet need exists in psychiatry for new and better treatments with novel mechanisms of action. Many guideline-recommended cardiovascular medications have a long track record, including a well-established safety profile with no surprises, and are available in generic versions. They can be developed for a new indication at minimal cost, noted Dr. De Picker, a psychiatrist at the University of Antwerp (Belgium).

The idea of psychiatric repurposing of drugs originally developed for nonpsychiatric indications is nothing new, she added. Examples include lithium for gout, valproate for epilepsy, and ketamine for anesthesiology.

One hitch in efforts to repurpose cardiovascular medications is that, when psychiatric patients have been included in randomized trials of the drugs’ cardiovascular effects, the psychiatric outcomes often went untallied.

Indeed, the only high-quality randomized trial evidence of psychiatric benefits for any class of cardiovascular medications is for statins, where a modest-sized meta-analysis of six placebo-controlled trials in 339 patients with schizophrenia showed the lipid-lowering agents had benefit for both positive and negative symptoms (Psychiatry Res. 2018 Apr;262:84-93). But that’s not a body of data of sufficient size to be definitive, in Dr. De Picker’s view.

Much of the recent enthusiasm for exploring the potential of cardiovascular drugs for psychiatric conditions comes from hypothesis-generating big data analyses drawn from Scandinavian national patient registries. Danish investigators scrutinized all 1.6 million Danes exposed to six classes of drugs of interest during 2005-2015 and determined that those on long-term statins, low-dose aspirin, ACE inhibitors, angiotensin receptor blockers, or allopurinol were associated with a decreased rate of new-onset depression, while high-dose aspirin and non-aspirin NSAIDs were associated with an increased rate, compared with a 30% random sample of the country’s population (Acta Psychiatr Scand. 2019 Jan;1391:68-77).

Similarly, the Danish group found that continued use of statins, angiotensin agents, or low-dose aspirin was associated with a decreased rate of new-onset bipolar disorder, while high-dose aspirin and other NSAIDs were linked to increased risk (Bipolar Disord. 2019 Aug;[15]:410-8). What these agents have in common, the investigators observed, is that they act on inflammation and potentially on the stress response system.

Meanwhile, Swedish investigators examined the course of 142,691 Swedes with a diagnosis of bipolar disorder, schizophrenia, or nonaffective psychosis during 2005-2016. They determined that, during periods when those individuals were on a statin, calcium channel blocker, or metformin, they had reduced rates of psychiatric hospitalization and self-harm (JAMA Psychiatry. 2019 Apr 1;76[4]:382-90).

Scottish researchers analyzed the health records of 144,066 patients placed on monotherapy for hypertension and determined that the lowest risk for hospitalization for a mood disorder during follow-up was in those prescribed an ACE inhibitor or angiotensin receptor blocker. The risk was significantly higher in patients on a beta-blocker or calcium channel blocker, and intermediate in those on a thiazide diuretic (Hypertension. 2016 Nov;68[5:1132-8).

“Obviously, this is all at a very macro scale and we have no idea whatsoever what this means for individual patients, number needed to treat, or which type of patients would benefit, but it does provide us with some guidance for future research,” according to Dr. De Picker.

In the meantime, while physicians await definitive evidence of any impact of cardiovascular drugs might have on psychiatric outcomes, abundant data exist underscoring what she called “shockingly high levels” of inadequate management of cardiovascular risk factors in patients with serious mental illness. That problem needs to be addressed, and Dr. De Picker offered her personal recommendations for doing so in a manner consistent with the evidence to date suggestive of potential mental health benefits of some cardiovascular medications.

She advised that, for treatment of hypertension in patients with bipolar disorder or major depression, an ACE inhibitor or angiotensin-converting enzyme inhibitor is preferred as first-line. There is some evidence to suggest lipophilic beta-blockers, which cross the blood-brain barrier, improve anxiety symptoms and panic attacks, and prevent memory consolidation in patients with posttraumatic stress disorder. But the Scottish data suggest that they may worsen mood disorders.

“I would be careful in using beta-blockers as first-line treatment for hypertension. They’re not in the guidelines for anxiety disorders. British guidelines recommend them to prevent memory consolidation in PTSD, but do not use them as first-line in patients with major depressive disorder or bipolar disorder,” she said. As for calcium channel blockers, the jury is still out, with mixed and inconsistent evidence to date as to the impact of this drug class on mental illness outcomes.

She recommended a very low threshold for prescribing statin therapy in patients with serious mental illness in light of the superb risk/benefit ratio for this drug class. She makes sure a statin is onboard in her patients with schizophrenia, major depressive disorder, or bipolar disorder who are over age 60. In her younger patients, she turns for guidance to an online calculator of an individual’s 10-year risk of a first acute MI or stroke.

Metformin has been shown to be beneficial for addressing the weight gain and other adverse metabolic effects caused by antipsychotic agents, and there is some preliminary evidence of improved psychiatric outcomes in patients with serious mental illness.

Christian Otte, MD, who also spoke at the session, noted that not only do emerging data point to the possibility that cardiovascular drugs might have benefit in terms of psychiatric outcomes, there is also some evidence, albeit mixed, that the converse is true: that is, psychiatric drugs may have cardiovascular benefits. He pointed to a South Korean trial in which 300 patients with a recent acute coronary syndrome and major depression were randomized to 24 weeks of escitalopram or placebo. At median 8.1 years of follow-up, the group that received the SSRI had a 31% relative risk reduction in the primary composite endpoint of all-cause mortality, acute MI, or percutaneous coronary intervention (JAMA. 2018 Jul 24; 320[4]:350–7).

“Potentially independent of their antidepressant effects, some SSRIs’ antiplatelet effects could be beneficial for patients with coronary heart disease, although the jury is still open regarding this question, with evidence in both directions,” said Dr. Otte, professor of psychiatry at Charite University Medical Center in Berlin.

Dr. De Picker offered an example as well: Finnish psychiatrists recently reported that cardiovascular mortality was reduced by an adjusted 38% during periods when 62,250 Finnish schizophrenia patients were on antipsychotic agents, compared with periods of nonuse of the drugs in a national study with a median 14.1 years of follow-up (World Psychiatry. 2020 Feb;19[1]:61-8).

“What they discovered – and this is quite contrary to what we are used to hearing about antipsychotic medication and cardiovascular risk – is that while the number of cardiovascular hospitalizations was not different in periods with or without antipsychotic use, the cardiovascular mortality was quite strikingly reduced when patients were on antipsychotic medication,” she said.

Asked by an audience member whether she personally prescribes metformin, Dr. De Picker replied: “Well, yes, why not? One of the very nice things about metformin is that it is actually a very safe drug, even in the hands of nonspecialists.

“I understand that maybe psychiatrists may not feel very comfortable in starting patients on metformin due to a lack of experience. But there are really only two things you need to take into account. About one-quarter of patients will experience GI side effects – nausea, vomiting, abdominal discomfort – and this can be reduced by gradually uptitrating the dose, dosing at mealtime, and using an extended-release formulation. And the second thing is that metformin can impair vitamin B₁₂ absorption, so I think, especially in psychiatric patients, it would be good to do an annual measurement of vitamin B₁₂ level and, if necessary, administer intramuscular supplements,” Dr. De Picker said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

SOURCE: De Picker L. ECNP 2020. Session EDU.05.

One of the hottest topics now in psychiatry is the possibility of repurposing long-established cardiovascular medications for treatment of patients with serious mental illness, Livia De Picker, MD, PhD, said at the virtual congress of the European College of Neuropsychopharmacology.

Courtesy Dr. Livia De Picker

The appeal is multifold. A huge unmet need exists in psychiatry for new and better treatments with novel mechanisms of action. Many guideline-recommended cardiovascular medications have a long track record, including a well-established safety profile with no surprises, and are available in generic versions. They can be developed for a new indication at minimal cost, noted Dr. De Picker, a psychiatrist at the University of Antwerp (Belgium).

The idea of psychiatric repurposing of drugs originally developed for nonpsychiatric indications is nothing new, she added. Examples include lithium for gout, valproate for epilepsy, and ketamine for anesthesiology.

One hitch in efforts to repurpose cardiovascular medications is that, when psychiatric patients have been included in randomized trials of the drugs’ cardiovascular effects, the psychiatric outcomes often went untallied.

Indeed, the only high-quality randomized trial evidence of psychiatric benefits for any class of cardiovascular medications is for statins, where a modest-sized meta-analysis of six placebo-controlled trials in 339 patients with schizophrenia showed the lipid-lowering agents had benefit for both positive and negative symptoms (Psychiatry Res. 2018 Apr;262:84-93). But that’s not a body of data of sufficient size to be definitive, in Dr. De Picker’s view.

Much of the recent enthusiasm for exploring the potential of cardiovascular drugs for psychiatric conditions comes from hypothesis-generating big data analyses drawn from Scandinavian national patient registries. Danish investigators scrutinized all 1.6 million Danes exposed to six classes of drugs of interest during 2005-2015 and determined that those on long-term statins, low-dose aspirin, ACE inhibitors, angiotensin receptor blockers, or allopurinol were associated with a decreased rate of new-onset depression, while high-dose aspirin and non-aspirin NSAIDs were associated with an increased rate, compared with a 30% random sample of the country’s population (Acta Psychiatr Scand. 2019 Jan;1391:68-77).

Similarly, the Danish group found that continued use of statins, angiotensin agents, or low-dose aspirin was associated with a decreased rate of new-onset bipolar disorder, while high-dose aspirin and other NSAIDs were linked to increased risk (Bipolar Disord. 2019 Aug;[15]:410-8). What these agents have in common, the investigators observed, is that they act on inflammation and potentially on the stress response system.

Meanwhile, Swedish investigators examined the course of 142,691 Swedes with a diagnosis of bipolar disorder, schizophrenia, or nonaffective psychosis during 2005-2016. They determined that, during periods when those individuals were on a statin, calcium channel blocker, or metformin, they had reduced rates of psychiatric hospitalization and self-harm (JAMA Psychiatry. 2019 Apr 1;76[4]:382-90).

Scottish researchers analyzed the health records of 144,066 patients placed on monotherapy for hypertension and determined that the lowest risk for hospitalization for a mood disorder during follow-up was in those prescribed an ACE inhibitor or angiotensin receptor blocker. The risk was significantly higher in patients on a beta-blocker or calcium channel blocker, and intermediate in those on a thiazide diuretic (Hypertension. 2016 Nov;68[5:1132-8).

“Obviously, this is all at a very macro scale and we have no idea whatsoever what this means for individual patients, number needed to treat, or which type of patients would benefit, but it does provide us with some guidance for future research,” according to Dr. De Picker.

In the meantime, while physicians await definitive evidence of any impact of cardiovascular drugs might have on psychiatric outcomes, abundant data exist underscoring what she called “shockingly high levels” of inadequate management of cardiovascular risk factors in patients with serious mental illness. That problem needs to be addressed, and Dr. De Picker offered her personal recommendations for doing so in a manner consistent with the evidence to date suggestive of potential mental health benefits of some cardiovascular medications.

She advised that, for treatment of hypertension in patients with bipolar disorder or major depression, an ACE inhibitor or angiotensin-converting enzyme inhibitor is preferred as first-line. There is some evidence to suggest lipophilic beta-blockers, which cross the blood-brain barrier, improve anxiety symptoms and panic attacks, and prevent memory consolidation in patients with posttraumatic stress disorder. But the Scottish data suggest that they may worsen mood disorders.

“I would be careful in using beta-blockers as first-line treatment for hypertension. They’re not in the guidelines for anxiety disorders. British guidelines recommend them to prevent memory consolidation in PTSD, but do not use them as first-line in patients with major depressive disorder or bipolar disorder,” she said. As for calcium channel blockers, the jury is still out, with mixed and inconsistent evidence to date as to the impact of this drug class on mental illness outcomes.

She recommended a very low threshold for prescribing statin therapy in patients with serious mental illness in light of the superb risk/benefit ratio for this drug class. She makes sure a statin is onboard in her patients with schizophrenia, major depressive disorder, or bipolar disorder who are over age 60. In her younger patients, she turns for guidance to an online calculator of an individual’s 10-year risk of a first acute MI or stroke.

Metformin has been shown to be beneficial for addressing the weight gain and other adverse metabolic effects caused by antipsychotic agents, and there is some preliminary evidence of improved psychiatric outcomes in patients with serious mental illness.

Christian Otte, MD, who also spoke at the session, noted that not only do emerging data point to the possibility that cardiovascular drugs might have benefit in terms of psychiatric outcomes, there is also some evidence, albeit mixed, that the converse is true: that is, psychiatric drugs may have cardiovascular benefits. He pointed to a South Korean trial in which 300 patients with a recent acute coronary syndrome and major depression were randomized to 24 weeks of escitalopram or placebo. At median 8.1 years of follow-up, the group that received the SSRI had a 31% relative risk reduction in the primary composite endpoint of all-cause mortality, acute MI, or percutaneous coronary intervention (JAMA. 2018 Jul 24; 320[4]:350–7).

“Potentially independent of their antidepressant effects, some SSRIs’ antiplatelet effects could be beneficial for patients with coronary heart disease, although the jury is still open regarding this question, with evidence in both directions,” said Dr. Otte, professor of psychiatry at Charite University Medical Center in Berlin.

Dr. De Picker offered an example as well: Finnish psychiatrists recently reported that cardiovascular mortality was reduced by an adjusted 38% during periods when 62,250 Finnish schizophrenia patients were on antipsychotic agents, compared with periods of nonuse of the drugs in a national study with a median 14.1 years of follow-up (World Psychiatry. 2020 Feb;19[1]:61-8).

“What they discovered – and this is quite contrary to what we are used to hearing about antipsychotic medication and cardiovascular risk – is that while the number of cardiovascular hospitalizations was not different in periods with or without antipsychotic use, the cardiovascular mortality was quite strikingly reduced when patients were on antipsychotic medication,” she said.

Asked by an audience member whether she personally prescribes metformin, Dr. De Picker replied: “Well, yes, why not? One of the very nice things about metformin is that it is actually a very safe drug, even in the hands of nonspecialists.

“I understand that maybe psychiatrists may not feel very comfortable in starting patients on metformin due to a lack of experience. But there are really only two things you need to take into account. About one-quarter of patients will experience GI side effects – nausea, vomiting, abdominal discomfort – and this can be reduced by gradually uptitrating the dose, dosing at mealtime, and using an extended-release formulation. And the second thing is that metformin can impair vitamin B₁₂ absorption, so I think, especially in psychiatric patients, it would be good to do an annual measurement of vitamin B₁₂ level and, if necessary, administer intramuscular supplements,” Dr. De Picker said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

SOURCE: De Picker L. ECNP 2020. Session EDU.05.

One of the hottest topics now in psychiatry is the possibility of repurposing long-established cardiovascular medications for treatment of patients with serious mental illness, Livia De Picker, MD, PhD, said at the virtual congress of the European College of Neuropsychopharmacology.

Courtesy Dr. Livia De Picker

The appeal is multifold. A huge unmet need exists in psychiatry for new and better treatments with novel mechanisms of action. Many guideline-recommended cardiovascular medications have a long track record, including a well-established safety profile with no surprises, and are available in generic versions. They can be developed for a new indication at minimal cost, noted Dr. De Picker, a psychiatrist at the University of Antwerp (Belgium).

The idea of psychiatric repurposing of drugs originally developed for nonpsychiatric indications is nothing new, she added. Examples include lithium for gout, valproate for epilepsy, and ketamine for anesthesiology.

One hitch in efforts to repurpose cardiovascular medications is that, when psychiatric patients have been included in randomized trials of the drugs’ cardiovascular effects, the psychiatric outcomes often went untallied.

Indeed, the only high-quality randomized trial evidence of psychiatric benefits for any class of cardiovascular medications is for statins, where a modest-sized meta-analysis of six placebo-controlled trials in 339 patients with schizophrenia showed the lipid-lowering agents had benefit for both positive and negative symptoms (Psychiatry Res. 2018 Apr;262:84-93). But that’s not a body of data of sufficient size to be definitive, in Dr. De Picker’s view.

Much of the recent enthusiasm for exploring the potential of cardiovascular drugs for psychiatric conditions comes from hypothesis-generating big data analyses drawn from Scandinavian national patient registries. Danish investigators scrutinized all 1.6 million Danes exposed to six classes of drugs of interest during 2005-2015 and determined that those on long-term statins, low-dose aspirin, ACE inhibitors, angiotensin receptor blockers, or allopurinol were associated with a decreased rate of new-onset depression, while high-dose aspirin and non-aspirin NSAIDs were associated with an increased rate, compared with a 30% random sample of the country’s population (Acta Psychiatr Scand. 2019 Jan;1391:68-77).

Similarly, the Danish group found that continued use of statins, angiotensin agents, or low-dose aspirin was associated with a decreased rate of new-onset bipolar disorder, while high-dose aspirin and other NSAIDs were linked to increased risk (Bipolar Disord. 2019 Aug;[15]:410-8). What these agents have in common, the investigators observed, is that they act on inflammation and potentially on the stress response system.

Meanwhile, Swedish investigators examined the course of 142,691 Swedes with a diagnosis of bipolar disorder, schizophrenia, or nonaffective psychosis during 2005-2016. They determined that, during periods when those individuals were on a statin, calcium channel blocker, or metformin, they had reduced rates of psychiatric hospitalization and self-harm (JAMA Psychiatry. 2019 Apr 1;76[4]:382-90).

Scottish researchers analyzed the health records of 144,066 patients placed on monotherapy for hypertension and determined that the lowest risk for hospitalization for a mood disorder during follow-up was in those prescribed an ACE inhibitor or angiotensin receptor blocker. The risk was significantly higher in patients on a beta-blocker or calcium channel blocker, and intermediate in those on a thiazide diuretic (Hypertension. 2016 Nov;68[5:1132-8).

“Obviously, this is all at a very macro scale and we have no idea whatsoever what this means for individual patients, number needed to treat, or which type of patients would benefit, but it does provide us with some guidance for future research,” according to Dr. De Picker.

In the meantime, while physicians await definitive evidence of any impact of cardiovascular drugs might have on psychiatric outcomes, abundant data exist underscoring what she called “shockingly high levels” of inadequate management of cardiovascular risk factors in patients with serious mental illness. That problem needs to be addressed, and Dr. De Picker offered her personal recommendations for doing so in a manner consistent with the evidence to date suggestive of potential mental health benefits of some cardiovascular medications.

She advised that, for treatment of hypertension in patients with bipolar disorder or major depression, an ACE inhibitor or angiotensin-converting enzyme inhibitor is preferred as first-line. There is some evidence to suggest lipophilic beta-blockers, which cross the blood-brain barrier, improve anxiety symptoms and panic attacks, and prevent memory consolidation in patients with posttraumatic stress disorder. But the Scottish data suggest that they may worsen mood disorders.

“I would be careful in using beta-blockers as first-line treatment for hypertension. They’re not in the guidelines for anxiety disorders. British guidelines recommend them to prevent memory consolidation in PTSD, but do not use them as first-line in patients with major depressive disorder or bipolar disorder,” she said. As for calcium channel blockers, the jury is still out, with mixed and inconsistent evidence to date as to the impact of this drug class on mental illness outcomes.

She recommended a very low threshold for prescribing statin therapy in patients with serious mental illness in light of the superb risk/benefit ratio for this drug class. She makes sure a statin is onboard in her patients with schizophrenia, major depressive disorder, or bipolar disorder who are over age 60. In her younger patients, she turns for guidance to an online calculator of an individual’s 10-year risk of a first acute MI or stroke.

Metformin has been shown to be beneficial for addressing the weight gain and other adverse metabolic effects caused by antipsychotic agents, and there is some preliminary evidence of improved psychiatric outcomes in patients with serious mental illness.

Christian Otte, MD, who also spoke at the session, noted that not only do emerging data point to the possibility that cardiovascular drugs might have benefit in terms of psychiatric outcomes, there is also some evidence, albeit mixed, that the converse is true: that is, psychiatric drugs may have cardiovascular benefits. He pointed to a South Korean trial in which 300 patients with a recent acute coronary syndrome and major depression were randomized to 24 weeks of escitalopram or placebo. At median 8.1 years of follow-up, the group that received the SSRI had a 31% relative risk reduction in the primary composite endpoint of all-cause mortality, acute MI, or percutaneous coronary intervention (JAMA. 2018 Jul 24; 320[4]:350–7).

“Potentially independent of their antidepressant effects, some SSRIs’ antiplatelet effects could be beneficial for patients with coronary heart disease, although the jury is still open regarding this question, with evidence in both directions,” said Dr. Otte, professor of psychiatry at Charite University Medical Center in Berlin.

Dr. De Picker offered an example as well: Finnish psychiatrists recently reported that cardiovascular mortality was reduced by an adjusted 38% during periods when 62,250 Finnish schizophrenia patients were on antipsychotic agents, compared with periods of nonuse of the drugs in a national study with a median 14.1 years of follow-up (World Psychiatry. 2020 Feb;19[1]:61-8).

“What they discovered – and this is quite contrary to what we are used to hearing about antipsychotic medication and cardiovascular risk – is that while the number of cardiovascular hospitalizations was not different in periods with or without antipsychotic use, the cardiovascular mortality was quite strikingly reduced when patients were on antipsychotic medication,” she said.

Asked by an audience member whether she personally prescribes metformin, Dr. De Picker replied: “Well, yes, why not? One of the very nice things about metformin is that it is actually a very safe drug, even in the hands of nonspecialists.

“I understand that maybe psychiatrists may not feel very comfortable in starting patients on metformin due to a lack of experience. But there are really only two things you need to take into account. About one-quarter of patients will experience GI side effects – nausea, vomiting, abdominal discomfort – and this can be reduced by gradually uptitrating the dose, dosing at mealtime, and using an extended-release formulation. And the second thing is that metformin can impair vitamin B₁₂ absorption, so I think, especially in psychiatric patients, it would be good to do an annual measurement of vitamin B₁₂ level and, if necessary, administer intramuscular supplements,” Dr. De Picker said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

SOURCE: De Picker L. ECNP 2020. Session EDU.05.

A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.

Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.

“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.

The study was published Sept. 30 in JAMA Network Open.
 

Negative impact

“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.

“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.

To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.

The median follow-up period was 8 days (interquartile range, 4-16 days) .

Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. The patients with psychiatric disorders were significantly older and were more likely to be women, White, non-Hispanic, and to have medical comorbidities (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).

Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
 

Vulnerability to stress

In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).

In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).

Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.

Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
 

Quality care

Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”

The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.

Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.

“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.

No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.

A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.

Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.

“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.

The study was published Sept. 30 in JAMA Network Open.
 

Negative impact

“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.

“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.

To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.

The median follow-up period was 8 days (interquartile range, 4-16 days) .

Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. The patients with psychiatric disorders were significantly older and were more likely to be women, White, non-Hispanic, and to have medical comorbidities (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).

Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
 

Vulnerability to stress

In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).

In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).

Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.

Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
 

Quality care

Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”

The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.

Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.

“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.

No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.

A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.

Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.

“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.

The study was published Sept. 30 in JAMA Network Open.
 

Negative impact

“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.

“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.

To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.

The median follow-up period was 8 days (interquartile range, 4-16 days) .

Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. The patients with psychiatric disorders were significantly older and were more likely to be women, White, non-Hispanic, and to have medical comorbidities (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).

Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
 

Vulnerability to stress

In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).

In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).

Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.

Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
 

Quality care

Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”

The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.

Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.

“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.

No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.

Magnetic seizure therapy (MST) appears to be a viable alternative to electroconvulsive therapy (ECT) in reducing suicide risk in patients with treatment-resistant depression (TRD), early research suggests.

In a single-center, open-label study, MST produced complete remission from suicidality in almost half of the patients who received the treatment.

“The results are promising,” lead author Cory R. Weissman, MD, Centre for Addiction and Mental Health, University of Toronto, told Medscape Medical News.

“The field needs new ways of approaching suicidality because it’s becoming a bigger issue and a major concern, especially now with COVID. These are early but promising results that need to be followed up,” Weissman said.

The study was published online August 18 in JAMA Network Open.
 

Fewer side effects, less stigma

MST is similar to ECT, which is an effective treatment for suicidality in mood disorders. However, ECT is underutilized – fewer than 1% of patients with TRD receive the treatment – because of stigma and/or a perceived risk of cognitive adverse effects, he said.

“MST is a focal magnetic pulse that leads to discharge or depolarization within the frontal lobe of the brain with the goal of inducing a seizure. It works quite similarly to ECT, which we know is quite a good anti-suicidal treatment, especially in depression,” Weissman explained

However, MST has fewer side effects, particularly on cognition, and less stigma compared to ECT. It also has a different mechanism of action, with a “more focal treatment target in the brain than ECT to induce seizures,” Weissman said.

The Toronto group has been studying MST in various mood disorders for several years. As previously reported by Medscape Medical News, MST is effective in reducing suicidal thoughts in treatment-resistant bipolar disorder. 

The current study is a post hoc secondary analysis of data from the group’s original trial of MST as a treatment for treatment resistant depression in patients initially referred for ECT. The trial ran from February 2012 through June 2019 and with a post-treatment 6-month follow-up.

The secondary analysis was performed from January 2019 to November 2019.

The secondary analysis included 67 patients who underwent MST 2 to 3 times per week until they achieved remission from a depressive episode or until they reached a maximum of 24 sessions. All had baseline suicidality, as defined by a score greater than 0 on the Beck Scale for Suicidal Ideation (Beck SSI).

MST was administered using the MagPro MST device with Twin Coil-XS (MagVenture) applied over the frontal cortex at 100% machine output with low (25 Hz), moderate (50 or 60 Hz), or high (100 Hz) frequency.

“It’s very similar to ECT. The actual seizure lasts about a minute or two, and patients recover in about 10 to 15 minutes and they go home afterwards,” Weissman said.

The main outcome was remission from suicidality as measured by an end-point score of 0 on the Beck SSI. Of the 67 patients, 32 (47.8%) achieved remission from suicidality.

Low and moderate frequencies appeared to be more effective for suicidality; 16 of 29 patients (55.2%) receiving low frequency MST achieved remission, as did 12 of 22 patients (54.5%) receiving moderate frequency MST. Four of 16 patients (25%) who received high frequency MST achieved remission from suicidality.
 

A “valuable contribution”

Commenting on the findings for Medscape Medical News, Manish K. Jha, MD, Icahn School of Medicine at Mount Sinai in New York City, said there is an urgent need to develop safe and effective treatment for patients with treatment-resistant depression (TRD).

“The Sequenced Treatment Alternative to Relieve Depression (STAR*D) trial showed that after inadequate improvement with two antidepressants, the likelihood of improvement with a third or fourth antidepressant trial was very low. Therefore, we need effective treatment for TRD,” noted Jha, who was not involved in the research.

The current study represents a “valuable contribution, as it shows improvement in suicidal ideation with magnetic seizure therapy,” he added.

The study’s findings suggest that MST may offer a “viable new treatment” for patients with TRD. He added that the upcoming results of an ongoing clinical trial testing MST against ECT are of “great interest to the field.”

Although the findings are compelling, Jha also noted the study had several limitations, include a relatively “modest” sample size and no sham or active comparator.

In addition, he said, the level of suicidality in this study was limited because of eligibility restrictions, such as exclusion of individuals who had attempted suicide in the prior 6 months.

“While authors use a broad term of ‘suicidality,’ their study is focused on suicidal ideation. Future studies that target suicide behavior are urgently needed. This may mean that we need to study individuals with recent suicide attempts in settings such as emergency rooms and inpatient units,” said Jha.

The study had no specific funding. Weissman has disclosed no relevant financial relationships. Several other study authors reported relationships with industry. The full list can be found with the original article. Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education.

This article first appeared on Medscape.com.

Magnetic seizure therapy (MST) appears to be a viable alternative to electroconvulsive therapy (ECT) in reducing suicide risk in patients with treatment-resistant depression (TRD), early research suggests.

In a single-center, open-label study, MST produced complete remission from suicidality in almost half of the patients who received the treatment.

“The results are promising,” lead author Cory R. Weissman, MD, Centre for Addiction and Mental Health, University of Toronto, told Medscape Medical News.

“The field needs new ways of approaching suicidality because it’s becoming a bigger issue and a major concern, especially now with COVID. These are early but promising results that need to be followed up,” Weissman said.

The study was published online August 18 in JAMA Network Open.
 

Fewer side effects, less stigma

MST is similar to ECT, which is an effective treatment for suicidality in mood disorders. However, ECT is underutilized – fewer than 1% of patients with TRD receive the treatment – because of stigma and/or a perceived risk of cognitive adverse effects, he said.

“MST is a focal magnetic pulse that leads to discharge or depolarization within the frontal lobe of the brain with the goal of inducing a seizure. It works quite similarly to ECT, which we know is quite a good anti-suicidal treatment, especially in depression,” Weissman explained

However, MST has fewer side effects, particularly on cognition, and less stigma compared to ECT. It also has a different mechanism of action, with a “more focal treatment target in the brain than ECT to induce seizures,” Weissman said.

The Toronto group has been studying MST in various mood disorders for several years. As previously reported by Medscape Medical News, MST is effective in reducing suicidal thoughts in treatment-resistant bipolar disorder. 

The current study is a post hoc secondary analysis of data from the group’s original trial of MST as a treatment for treatment resistant depression in patients initially referred for ECT. The trial ran from February 2012 through June 2019 and with a post-treatment 6-month follow-up.

The secondary analysis was performed from January 2019 to November 2019.

The secondary analysis included 67 patients who underwent MST 2 to 3 times per week until they achieved remission from a depressive episode or until they reached a maximum of 24 sessions. All had baseline suicidality, as defined by a score greater than 0 on the Beck Scale for Suicidal Ideation (Beck SSI).

MST was administered using the MagPro MST device with Twin Coil-XS (MagVenture) applied over the frontal cortex at 100% machine output with low (25 Hz), moderate (50 or 60 Hz), or high (100 Hz) frequency.

“It’s very similar to ECT. The actual seizure lasts about a minute or two, and patients recover in about 10 to 15 minutes and they go home afterwards,” Weissman said.

The main outcome was remission from suicidality as measured by an end-point score of 0 on the Beck SSI. Of the 67 patients, 32 (47.8%) achieved remission from suicidality.

Low and moderate frequencies appeared to be more effective for suicidality; 16 of 29 patients (55.2%) receiving low frequency MST achieved remission, as did 12 of 22 patients (54.5%) receiving moderate frequency MST. Four of 16 patients (25%) who received high frequency MST achieved remission from suicidality.
 

A “valuable contribution”

Commenting on the findings for Medscape Medical News, Manish K. Jha, MD, Icahn School of Medicine at Mount Sinai in New York City, said there is an urgent need to develop safe and effective treatment for patients with treatment-resistant depression (TRD).

“The Sequenced Treatment Alternative to Relieve Depression (STAR*D) trial showed that after inadequate improvement with two antidepressants, the likelihood of improvement with a third or fourth antidepressant trial was very low. Therefore, we need effective treatment for TRD,” noted Jha, who was not involved in the research.

The current study represents a “valuable contribution, as it shows improvement in suicidal ideation with magnetic seizure therapy,” he added.

The study’s findings suggest that MST may offer a “viable new treatment” for patients with TRD. He added that the upcoming results of an ongoing clinical trial testing MST against ECT are of “great interest to the field.”

Although the findings are compelling, Jha also noted the study had several limitations, include a relatively “modest” sample size and no sham or active comparator.

In addition, he said, the level of suicidality in this study was limited because of eligibility restrictions, such as exclusion of individuals who had attempted suicide in the prior 6 months.

“While authors use a broad term of ‘suicidality,’ their study is focused on suicidal ideation. Future studies that target suicide behavior are urgently needed. This may mean that we need to study individuals with recent suicide attempts in settings such as emergency rooms and inpatient units,” said Jha.

The study had no specific funding. Weissman has disclosed no relevant financial relationships. Several other study authors reported relationships with industry. The full list can be found with the original article. Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education.

This article first appeared on Medscape.com.

Magnetic seizure therapy (MST) appears to be a viable alternative to electroconvulsive therapy (ECT) in reducing suicide risk in patients with treatment-resistant depression (TRD), early research suggests.

In a single-center, open-label study, MST produced complete remission from suicidality in almost half of the patients who received the treatment.

“The results are promising,” lead author Cory R. Weissman, MD, Centre for Addiction and Mental Health, University of Toronto, told Medscape Medical News.

“The field needs new ways of approaching suicidality because it’s becoming a bigger issue and a major concern, especially now with COVID. These are early but promising results that need to be followed up,” Weissman said.

The study was published online August 18 in JAMA Network Open.
 

Fewer side effects, less stigma

MST is similar to ECT, which is an effective treatment for suicidality in mood disorders. However, ECT is underutilized – fewer than 1% of patients with TRD receive the treatment – because of stigma and/or a perceived risk of cognitive adverse effects, he said.

“MST is a focal magnetic pulse that leads to discharge or depolarization within the frontal lobe of the brain with the goal of inducing a seizure. It works quite similarly to ECT, which we know is quite a good anti-suicidal treatment, especially in depression,” Weissman explained

However, MST has fewer side effects, particularly on cognition, and less stigma compared to ECT. It also has a different mechanism of action, with a “more focal treatment target in the brain than ECT to induce seizures,” Weissman said.

The Toronto group has been studying MST in various mood disorders for several years. As previously reported by Medscape Medical News, MST is effective in reducing suicidal thoughts in treatment-resistant bipolar disorder. 

The current study is a post hoc secondary analysis of data from the group’s original trial of MST as a treatment for treatment resistant depression in patients initially referred for ECT. The trial ran from February 2012 through June 2019 and with a post-treatment 6-month follow-up.

The secondary analysis was performed from January 2019 to November 2019.

The secondary analysis included 67 patients who underwent MST 2 to 3 times per week until they achieved remission from a depressive episode or until they reached a maximum of 24 sessions. All had baseline suicidality, as defined by a score greater than 0 on the Beck Scale for Suicidal Ideation (Beck SSI).

MST was administered using the MagPro MST device with Twin Coil-XS (MagVenture) applied over the frontal cortex at 100% machine output with low (25 Hz), moderate (50 or 60 Hz), or high (100 Hz) frequency.

“It’s very similar to ECT. The actual seizure lasts about a minute or two, and patients recover in about 10 to 15 minutes and they go home afterwards,” Weissman said.

The main outcome was remission from suicidality as measured by an end-point score of 0 on the Beck SSI. Of the 67 patients, 32 (47.8%) achieved remission from suicidality.

Low and moderate frequencies appeared to be more effective for suicidality; 16 of 29 patients (55.2%) receiving low frequency MST achieved remission, as did 12 of 22 patients (54.5%) receiving moderate frequency MST. Four of 16 patients (25%) who received high frequency MST achieved remission from suicidality.
 

A “valuable contribution”

Commenting on the findings for Medscape Medical News, Manish K. Jha, MD, Icahn School of Medicine at Mount Sinai in New York City, said there is an urgent need to develop safe and effective treatment for patients with treatment-resistant depression (TRD).

“The Sequenced Treatment Alternative to Relieve Depression (STAR*D) trial showed that after inadequate improvement with two antidepressants, the likelihood of improvement with a third or fourth antidepressant trial was very low. Therefore, we need effective treatment for TRD,” noted Jha, who was not involved in the research.

The current study represents a “valuable contribution, as it shows improvement in suicidal ideation with magnetic seizure therapy,” he added.

The study’s findings suggest that MST may offer a “viable new treatment” for patients with TRD. He added that the upcoming results of an ongoing clinical trial testing MST against ECT are of “great interest to the field.”

Although the findings are compelling, Jha also noted the study had several limitations, include a relatively “modest” sample size and no sham or active comparator.

In addition, he said, the level of suicidality in this study was limited because of eligibility restrictions, such as exclusion of individuals who had attempted suicide in the prior 6 months.

“While authors use a broad term of ‘suicidality,’ their study is focused on suicidal ideation. Future studies that target suicide behavior are urgently needed. This may mean that we need to study individuals with recent suicide attempts in settings such as emergency rooms and inpatient units,” said Jha.

The study had no specific funding. Weissman has disclosed no relevant financial relationships. Several other study authors reported relationships with industry. The full list can be found with the original article. Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education.

This article first appeared on Medscape.com.

Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.

Courtney Hale/Getty Images

“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”

But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.

Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.

Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.

In particular, the perinatal period is a time of great risk for depression and anxiety. Women are also at risk for postpartum depression, particularly women with bipolar disorder, Dr. Nasrallah said.

“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.

If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.

The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.

So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.

Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.

“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial disclosures.

Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.

Courtney Hale/Getty Images

“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”

But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.

Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.

Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.

In particular, the perinatal period is a time of great risk for depression and anxiety. Women are also at risk for postpartum depression, particularly women with bipolar disorder, Dr. Nasrallah said.

“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.

If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.

The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.

So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.

Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.

“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial disclosures.

Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.

Courtney Hale/Getty Images

“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”

But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.

Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.

Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.

In particular, the perinatal period is a time of great risk for depression and anxiety. Women are also at risk for postpartum depression, particularly women with bipolar disorder, Dr. Nasrallah said.

“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.

If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.

The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.

So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.

Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.

“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial disclosures.

Pediatric acute-onset neuropsychiatric syndrome (PANS), a rare acute onset of psychiatric symptoms, might be more common than initially thought, according to Kiki D. Chang, MD.

PANS is characterized by the National Center for Advancing Translational Sciences Genetic and Rare Diseases Information Center as a “sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms.” These symptoms can include anxiety, depression, oppositional behavior, difficulty concentrating, abnormalities in motor and sensory skills, and other somatic symptoms. The condition develops as a result of an infection that causes an autoimmune or inflammatory response in the brain, and patients tend to respond well to treatment from antibiotics, anti-inflammatory medication, and immunomodulatory therapy.

Both PANS and a subtype condition, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections (PANDAS), are underrecognized, Dr. Chang said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. It is often misdiagnosed as Tourette syndrome or obsessive-compulsive disorder (OCD) because tics are present in about half of cases, he said, but more severe associated symptoms, such as psychosis, can be misdiagnosed as psychotic disorders or mood disorders. Currently, neither PANS nor PANDAS are officially recognized by the American Academy of Pediatrics or the DSM-5.

“We’re hoping that it is soon because it clearly exists,” Dr. Chang said at the meeting, presented by Global Academy for Medical Education. “If you’ve ever treated a child with PANS or PANDAS and you have seen antibiotics totally reverse OCD and tic-like behavior, if you’ve seen prednisone actually treat symptoms of mania or even psychosis and actually make those things better rather than worse, it’s really eye-opening and it makes a believer out of you.”

Anxiety is the most common psychiatric symptom in youth, and anxiety disorders are also common, said Dr. Chang. According to the National Comorbidity Survey: Adolescent Supplement, 2001-2004, 31.9% adolescents overall reported an anxiety disorder, and 8.3% said their anxiety disorder caused severe impairment. The COVID-19 pandemic has increased the level of anxiety for children and adolescents, which can lead to other disorders, such as separation anxiety disorder, panic disorder, specific phobia, social anxiety disorder, acute stress disorder, generalized anxiety disorder, OCD, or posttraumatic stress disorder. Psychiatrists should be suspicious of any sudden onset of symptoms that overlap with PANS, said Dr. Chang, who is now in private practice in Palo Alto, Calif.

“Anxiety disorders are incredibly common. Remember that you’ve got to carefully screen for other anxiety disorders, because they’re highly comorbid,” Dr. Chang said. “You’ve got to do a full workup. If there are other things going on, you’ve got to think PANS. If it’s acute onset, you’ve really got to think [PANS], and you should do that workup or refer to someone who does.”

The prevalence of PANS and PANDAS is not known, but it may be more common than psychiatrists realize, Dr. Chang said. “I’ve been doing this for about 10 years now in the PANS and PANDAS field, and it’s very clear to me that this is something that is prevalent,” he said.

Together with Jennifer Frankovich, MD, Dr. Chang founded a clinic at the Lucile Packard Children’s Hospital Stanford, and also helped to develop treatment guidelines for youth with PANS. At the clinic, patients are approximately 7.7 years old when developing the first symptoms, and are 10.7 years old when presenting for treatment. Most patients at the clinic are male (78%), and 40% are acute onset cases. Nearly all patients have symptoms of anxiety (92%), mood disorder (88%), OCD (86%), sensory/motor abnormalities (88%), irritability/aggression (82%), somatic symptoms, deterioration in school (76%), and behavioral regression (59%). More than one-third present with suicidal ideation (38%) and violence to themselves (29%), others (38%), or objects. About one-fourth have symptoms of psychosis (24%).

“These can be really sick kids,” Dr. Chang said. “We’re talking about kids yelling, screaming, having anxiety attacks, dropping on the floor, doing rituals constantly, not functioning, not able to eat because they’re afraid of things, not able to take care of their body or daily living. These were sometimes highly functional people beforehand, sometimes they weren’t, but it was still an acute change.”
 

Treatment for PANS

Treatment guidelines released by the PANS/PANDAS Consortium in 2017 recommend a first course of antistreptococcal treatment for new PANS cases. Psychiatrists should look for evidence of strep or other infection and use antibiotics to eradicate any underlying acute or residual infection.

“Very commonly, we’ll use things like azithromycin, or Augmentin, or amoxicillin, and you’ll see suddenly the OCD go away or at least diminish, the sleep return to normal, the mood come back down,” Dr. Chang said. “It’s pretty amazing when you see it.”

In other cases, ongoing treatment is needed for longer than the normal 5-day or 10-day course of antibiotics. “We’re not exactly sure how long: sometimes it’s 3 weeks, sometimes it’s 4 weeks, but you have to give it more than a week. Sometimes it’s the anti-inflammatory properties that are helping.” While concerns about haphazardly prescribing antibiotics are valid, “if you can cure this stuff on antibiotics, it’s low-hanging fruit,” Dr. Chang said.

There is evidence in the literature that prescribing antibiotics for PANS is beneficial. A randomized controlled trial published in 2017 showed that patients with PANS prescribed azithromycin for 4 weeks had greater reductions in severity of OCD, compared with placebo.

“We need more studies, but clearly, antibiotics do have the potential to help with certain kids. And certainly, in my practice, I see sometimes a slam-dunk response,” Dr. Chang said. “Unfortunately, sometimes you don’t see a slam-dunk response or you can’t find an infection. That’s when it might be more of an inflammation from some other reason. It could be a leftover infection, or it could be an anti-inflammatory situation.”

Immunomodulatory treatment for PANS includes use of NSAIDs, such as ibuprofen or naproxen sodium; steroids, such as prednisone or intravenous corticosteroids; intravenous immunoglobulin; or plasma exchange. Other therapies to consider are rituximab, mycophenolate mofetil, and cyclophosphamide.

Some psychiatric treatments may help patients with PANS. While there is no empirical evidence that psychotropics are effective in treating PANS, some SSRIs might help if patients are able to handle any adverse events. Psychotherapy and education of the family are also important for patients with PANS and their caregivers.

“Basically, [PANS] has as high a caregiver burden as having someone in the household with Alzheimer’s disease or cancer. It’s a huge burden, it’s very stressful, and the family needs support for this,” Dr. Chang said.

Global Academy and this news organization are owned by the same parent company. Dr. Chang reports he is a consultant for Allergan, Impel NeuroPharma, and Sunovion. He is also on the speaker’s bureau for Sunovion.

Pediatric acute-onset neuropsychiatric syndrome (PANS), a rare acute onset of psychiatric symptoms, might be more common than initially thought, according to Kiki D. Chang, MD.

PANS is characterized by the National Center for Advancing Translational Sciences Genetic and Rare Diseases Information Center as a “sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms.” These symptoms can include anxiety, depression, oppositional behavior, difficulty concentrating, abnormalities in motor and sensory skills, and other somatic symptoms. The condition develops as a result of an infection that causes an autoimmune or inflammatory response in the brain, and patients tend to respond well to treatment from antibiotics, anti-inflammatory medication, and immunomodulatory therapy.

Both PANS and a subtype condition, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections (PANDAS), are underrecognized, Dr. Chang said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. It is often misdiagnosed as Tourette syndrome or obsessive-compulsive disorder (OCD) because tics are present in about half of cases, he said, but more severe associated symptoms, such as psychosis, can be misdiagnosed as psychotic disorders or mood disorders. Currently, neither PANS nor PANDAS are officially recognized by the American Academy of Pediatrics or the DSM-5.

“We’re hoping that it is soon because it clearly exists,” Dr. Chang said at the meeting, presented by Global Academy for Medical Education. “If you’ve ever treated a child with PANS or PANDAS and you have seen antibiotics totally reverse OCD and tic-like behavior, if you’ve seen prednisone actually treat symptoms of mania or even psychosis and actually make those things better rather than worse, it’s really eye-opening and it makes a believer out of you.”

Anxiety is the most common psychiatric symptom in youth, and anxiety disorders are also common, said Dr. Chang. According to the National Comorbidity Survey: Adolescent Supplement, 2001-2004, 31.9% adolescents overall reported an anxiety disorder, and 8.3% said their anxiety disorder caused severe impairment. The COVID-19 pandemic has increased the level of anxiety for children and adolescents, which can lead to other disorders, such as separation anxiety disorder, panic disorder, specific phobia, social anxiety disorder, acute stress disorder, generalized anxiety disorder, OCD, or posttraumatic stress disorder. Psychiatrists should be suspicious of any sudden onset of symptoms that overlap with PANS, said Dr. Chang, who is now in private practice in Palo Alto, Calif.

“Anxiety disorders are incredibly common. Remember that you’ve got to carefully screen for other anxiety disorders, because they’re highly comorbid,” Dr. Chang said. “You’ve got to do a full workup. If there are other things going on, you’ve got to think PANS. If it’s acute onset, you’ve really got to think [PANS], and you should do that workup or refer to someone who does.”

The prevalence of PANS and PANDAS is not known, but it may be more common than psychiatrists realize, Dr. Chang said. “I’ve been doing this for about 10 years now in the PANS and PANDAS field, and it’s very clear to me that this is something that is prevalent,” he said.

Together with Jennifer Frankovich, MD, Dr. Chang founded a clinic at the Lucile Packard Children’s Hospital Stanford, and also helped to develop treatment guidelines for youth with PANS. At the clinic, patients are approximately 7.7 years old when developing the first symptoms, and are 10.7 years old when presenting for treatment. Most patients at the clinic are male (78%), and 40% are acute onset cases. Nearly all patients have symptoms of anxiety (92%), mood disorder (88%), OCD (86%), sensory/motor abnormalities (88%), irritability/aggression (82%), somatic symptoms, deterioration in school (76%), and behavioral regression (59%). More than one-third present with suicidal ideation (38%) and violence to themselves (29%), others (38%), or objects. About one-fourth have symptoms of psychosis (24%).

“These can be really sick kids,” Dr. Chang said. “We’re talking about kids yelling, screaming, having anxiety attacks, dropping on the floor, doing rituals constantly, not functioning, not able to eat because they’re afraid of things, not able to take care of their body or daily living. These were sometimes highly functional people beforehand, sometimes they weren’t, but it was still an acute change.”
 

Treatment for PANS

Treatment guidelines released by the PANS/PANDAS Consortium in 2017 recommend a first course of antistreptococcal treatment for new PANS cases. Psychiatrists should look for evidence of strep or other infection and use antibiotics to eradicate any underlying acute or residual infection.

“Very commonly, we’ll use things like azithromycin, or Augmentin, or amoxicillin, and you’ll see suddenly the OCD go away or at least diminish, the sleep return to normal, the mood come back down,” Dr. Chang said. “It’s pretty amazing when you see it.”

In other cases, ongoing treatment is needed for longer than the normal 5-day or 10-day course of antibiotics. “We’re not exactly sure how long: sometimes it’s 3 weeks, sometimes it’s 4 weeks, but you have to give it more than a week. Sometimes it’s the anti-inflammatory properties that are helping.” While concerns about haphazardly prescribing antibiotics are valid, “if you can cure this stuff on antibiotics, it’s low-hanging fruit,” Dr. Chang said.

There is evidence in the literature that prescribing antibiotics for PANS is beneficial. A randomized controlled trial published in 2017 showed that patients with PANS prescribed azithromycin for 4 weeks had greater reductions in severity of OCD, compared with placebo.

“We need more studies, but clearly, antibiotics do have the potential to help with certain kids. And certainly, in my practice, I see sometimes a slam-dunk response,” Dr. Chang said. “Unfortunately, sometimes you don’t see a slam-dunk response or you can’t find an infection. That’s when it might be more of an inflammation from some other reason. It could be a leftover infection, or it could be an anti-inflammatory situation.”

Immunomodulatory treatment for PANS includes use of NSAIDs, such as ibuprofen or naproxen sodium; steroids, such as prednisone or intravenous corticosteroids; intravenous immunoglobulin; or plasma exchange. Other therapies to consider are rituximab, mycophenolate mofetil, and cyclophosphamide.

Some psychiatric treatments may help patients with PANS. While there is no empirical evidence that psychotropics are effective in treating PANS, some SSRIs might help if patients are able to handle any adverse events. Psychotherapy and education of the family are also important for patients with PANS and their caregivers.

“Basically, [PANS] has as high a caregiver burden as having someone in the household with Alzheimer’s disease or cancer. It’s a huge burden, it’s very stressful, and the family needs support for this,” Dr. Chang said.

Global Academy and this news organization are owned by the same parent company. Dr. Chang reports he is a consultant for Allergan, Impel NeuroPharma, and Sunovion. He is also on the speaker’s bureau for Sunovion.

Pediatric acute-onset neuropsychiatric syndrome (PANS), a rare acute onset of psychiatric symptoms, might be more common than initially thought, according to Kiki D. Chang, MD.

PANS is characterized by the National Center for Advancing Translational Sciences Genetic and Rare Diseases Information Center as a “sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms.” These symptoms can include anxiety, depression, oppositional behavior, difficulty concentrating, abnormalities in motor and sensory skills, and other somatic symptoms. The condition develops as a result of an infection that causes an autoimmune or inflammatory response in the brain, and patients tend to respond well to treatment from antibiotics, anti-inflammatory medication, and immunomodulatory therapy.

Both PANS and a subtype condition, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections (PANDAS), are underrecognized, Dr. Chang said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. It is often misdiagnosed as Tourette syndrome or obsessive-compulsive disorder (OCD) because tics are present in about half of cases, he said, but more severe associated symptoms, such as psychosis, can be misdiagnosed as psychotic disorders or mood disorders. Currently, neither PANS nor PANDAS are officially recognized by the American Academy of Pediatrics or the DSM-5.

“We’re hoping that it is soon because it clearly exists,” Dr. Chang said at the meeting, presented by Global Academy for Medical Education. “If you’ve ever treated a child with PANS or PANDAS and you have seen antibiotics totally reverse OCD and tic-like behavior, if you’ve seen prednisone actually treat symptoms of mania or even psychosis and actually make those things better rather than worse, it’s really eye-opening and it makes a believer out of you.”

Anxiety is the most common psychiatric symptom in youth, and anxiety disorders are also common, said Dr. Chang. According to the National Comorbidity Survey: Adolescent Supplement, 2001-2004, 31.9% adolescents overall reported an anxiety disorder, and 8.3% said their anxiety disorder caused severe impairment. The COVID-19 pandemic has increased the level of anxiety for children and adolescents, which can lead to other disorders, such as separation anxiety disorder, panic disorder, specific phobia, social anxiety disorder, acute stress disorder, generalized anxiety disorder, OCD, or posttraumatic stress disorder. Psychiatrists should be suspicious of any sudden onset of symptoms that overlap with PANS, said Dr. Chang, who is now in private practice in Palo Alto, Calif.

“Anxiety disorders are incredibly common. Remember that you’ve got to carefully screen for other anxiety disorders, because they’re highly comorbid,” Dr. Chang said. “You’ve got to do a full workup. If there are other things going on, you’ve got to think PANS. If it’s acute onset, you’ve really got to think [PANS], and you should do that workup or refer to someone who does.”

The prevalence of PANS and PANDAS is not known, but it may be more common than psychiatrists realize, Dr. Chang said. “I’ve been doing this for about 10 years now in the PANS and PANDAS field, and it’s very clear to me that this is something that is prevalent,” he said.

Together with Jennifer Frankovich, MD, Dr. Chang founded a clinic at the Lucile Packard Children’s Hospital Stanford, and also helped to develop treatment guidelines for youth with PANS. At the clinic, patients are approximately 7.7 years old when developing the first symptoms, and are 10.7 years old when presenting for treatment. Most patients at the clinic are male (78%), and 40% are acute onset cases. Nearly all patients have symptoms of anxiety (92%), mood disorder (88%), OCD (86%), sensory/motor abnormalities (88%), irritability/aggression (82%), somatic symptoms, deterioration in school (76%), and behavioral regression (59%). More than one-third present with suicidal ideation (38%) and violence to themselves (29%), others (38%), or objects. About one-fourth have symptoms of psychosis (24%).

“These can be really sick kids,” Dr. Chang said. “We’re talking about kids yelling, screaming, having anxiety attacks, dropping on the floor, doing rituals constantly, not functioning, not able to eat because they’re afraid of things, not able to take care of their body or daily living. These were sometimes highly functional people beforehand, sometimes they weren’t, but it was still an acute change.”
 

Treatment for PANS

Treatment guidelines released by the PANS/PANDAS Consortium in 2017 recommend a first course of antistreptococcal treatment for new PANS cases. Psychiatrists should look for evidence of strep or other infection and use antibiotics to eradicate any underlying acute or residual infection.

“Very commonly, we’ll use things like azithromycin, or Augmentin, or amoxicillin, and you’ll see suddenly the OCD go away or at least diminish, the sleep return to normal, the mood come back down,” Dr. Chang said. “It’s pretty amazing when you see it.”

In other cases, ongoing treatment is needed for longer than the normal 5-day or 10-day course of antibiotics. “We’re not exactly sure how long: sometimes it’s 3 weeks, sometimes it’s 4 weeks, but you have to give it more than a week. Sometimes it’s the anti-inflammatory properties that are helping.” While concerns about haphazardly prescribing antibiotics are valid, “if you can cure this stuff on antibiotics, it’s low-hanging fruit,” Dr. Chang said.

There is evidence in the literature that prescribing antibiotics for PANS is beneficial. A randomized controlled trial published in 2017 showed that patients with PANS prescribed azithromycin for 4 weeks had greater reductions in severity of OCD, compared with placebo.

“We need more studies, but clearly, antibiotics do have the potential to help with certain kids. And certainly, in my practice, I see sometimes a slam-dunk response,” Dr. Chang said. “Unfortunately, sometimes you don’t see a slam-dunk response or you can’t find an infection. That’s when it might be more of an inflammation from some other reason. It could be a leftover infection, or it could be an anti-inflammatory situation.”

Immunomodulatory treatment for PANS includes use of NSAIDs, such as ibuprofen or naproxen sodium; steroids, such as prednisone or intravenous corticosteroids; intravenous immunoglobulin; or plasma exchange. Other therapies to consider are rituximab, mycophenolate mofetil, and cyclophosphamide.

Some psychiatric treatments may help patients with PANS. While there is no empirical evidence that psychotropics are effective in treating PANS, some SSRIs might help if patients are able to handle any adverse events. Psychotherapy and education of the family are also important for patients with PANS and their caregivers.

“Basically, [PANS] has as high a caregiver burden as having someone in the household with Alzheimer’s disease or cancer. It’s a huge burden, it’s very stressful, and the family needs support for this,” Dr. Chang said.

Global Academy and this news organization are owned by the same parent company. Dr. Chang reports he is a consultant for Allergan, Impel NeuroPharma, and Sunovion. He is also on the speaker’s bureau for Sunovion.

An elderly, retired, married African American man sought psychiatric treatment for depression and suicidal thoughts. He had a detailed, lethal suicide plan, but he had not taken any steps to carry it out.

He met DSM-5 criteria for a major depressive episode, and he described a lifelong history of recurrent depressions as well as hypomanic episodes. He was diagnosed with bipolar II disorder, and he began weekly therapy, as well as medication. Despite several static and dynamic suicide risk factors, the psychiatrist also noted that he was help seeking and future oriented. He seemed transparent during his initial appointments. He did not have access to lethal means and welcomed the psychiatrist to communicate openly with his spouse.

The patient had never attempted suicide, there was no family history of suicide, and there was no psychosis or substance use disorder present. He was able to commit to reaching out to the psychiatrist, his spouse, or emergency personnel in the case of worsening suicidal thoughts or imminent suicidal action. He remained in the outpatient setting. His suicidal ideation faded and depression receded as psychotherapy and pharmacotherapy continued.

Discussion

Depression and suicidal ideation are ubiquitous in the practice of psychiatry. Psychiatrists draw from an array of assessment and management tools when this common clinical challenge arises. Among these tools is the no-suicide contract (NSC). The NSC goes by many names, including the no-harm contract and suicide prevention contract.¹ It is a promise, verbal or written, from the patient to not attempt suicide and to tell a loved one or psychiatric provider instead.² The verbal exchange between the patient and therapist described in the case fits the widely accepted clinical definition of an NSC. The contents and implementation of NSCs vary greatly; no standard approach is taught in psychiatric training.³ The American Psychiatric Association has warned against over-reliance on them, emphasizing that they have not been proven effective. It advises that NSCs should not be used independently of other tools or outside well-established patient-provider relationships.⁴ A 2007 review of the literature on NSCs concluded that there were no data to support their effectiveness and some data that they might even cause harm.⁵

The origin of the NSC

The NSC is fairly young and its foundation arguably weak. Its evolution has been traced back to a study published in 1973 by Robert C. Drye, MD, and associates on the effectiveness of a questionnaire for the assessment of suicide risk.⁶ The questionnaire centered on the patient’s reaction to the statement, “No matter what happens, I will not kill myself, accidently or on purpose, at any time.” The authors placed special emphasis on the words “I will,” which they felt to be a stronger indicator of commitment to safety than “I promise.” The authors thought the latter statement sounded like a child’s empty reply to a demanding parent. The authors reported a 100% success rate with “approximately 600 patients” across geographic regions and clinical settings.⁷ The study group is not further described, and that the authors contend that the intervention had “complete effectiveness in evaluating suicide risk” should give pause to anyone aiming to practice evidence-based psychiatry.

The theoretical basis of the NSC has been presumed by others to be based, in part, on the principles of transactional analysis. Specifically, the suicidal patient is seen as occupying the child ego state, and the NSC is seen as a means of moving the patient into the less problematic adult ego state. It has been argued, however, that an NSC can achieve exactly the opposite. The contract can pit the patient against the clinician, entrenching the patient deeper into the child ego and, therefore, suicidal state.⁸

Michael Craig Miller, MD, and associates proposed other psychological reasons why NSCs may be counterproductive. They write, “Psychological pitfalls abound, and any of them may contribute to a contract being thoughtless, unrealistic, irrelevant, cynical, punitive, or coercive.”⁹ They postulated that the NSC grew out of and assumes the same shared decision-making inherent in any therapeutic contract – and they argue that this assumption is flawed given the legal power clinicians have over suicidal patients. While acknowledging this problematic power differential, the authors go on to urge clinicians to aim for shared decision-making and a shared burden of risk when discussing treatment with suicidal patients.

Possible NSC common factors

Psychiatry, like the rest of medicine, is increasingly practiced in an evidence-based manner. The NSC should not be excluded from this movement. To this end, a recently published, randomized study of 97 active duty Army personnel seeking emergency behavioral health evaluation compared the effectiveness of NSCs and with an alternative intervention, the crisis response plan (CRP). The CRP was chosen because it had been suggested by the Joint Commision as an alternative to the NSC, although it also has little evidence supporting its use.¹⁰

The NSC and CRP interventions of the Army study were very similar. Both included suicide risk assessment, supportive listening, provision of crisis resources, and referral to treatment. In addition, the NSC intervention included asking whether the patients could keep themselves safe at home. The CRP intervention included collaboration with the patient to identify warning signs of crisis, self-management skills, and support persons. A seemingly small but interesting difference between the two interventions was which member of the dyad, patient or clinician, created a written record of the discussion. In the NSC group, the assessor did the writing, while in the CRP group, the patient controlled the pen.

The results of the study were intriguing. Suicidal ideation declined faster in the CRP arm. Participants in the CRP arm were 76% less likely to attempt suicide over 6 months, although this effect decreased and lost statistical significance when controlling for baseline severity of suicidal ideation. Despite those promising data, the only completed suicide was in the CRP arm.

The authors compared the makeup of the CRP intervention with key components of dialectical behavior therapy (DBT). They pointed to a 2015 study by Marsha Linehan, PhD, and associates that sought to identify the active ingredients of DBT. The Linehan study indicated that attending to warning signs and using self-management tools and social supports contributed more to the success of DBT than the individual therapy component. Interestingly, these were the same features that set the CRP intervention apart from the NSC in the Army study. Perhaps these are the common factors of effective counseling of suicidal patients.

Indeed, these factors seem to harken back to the NSC as originally envisioned by the late Dr. Drye – a patient-driven collaboration. Dr. Drye and associates wrote: “This approach developed out of our belief that the only therapeutic contracts likely to lead to change are those developed by the patient himself, for which he will assume responsibility.” While the data presented by Dr. Drye and associates were weak, the theory behind their NSC – patient commitment – seems solid. Commitment strategies, which grew out of social psychology, are effective and heavily used in DBT, including to decrease suicidal behaviors.¹¹

Conclusion

Suicidologist Shawn Christopher Shea, MD, argues that the answer to whether or not NSCs can work is conditional on the unique combination of patient, clinician, and therapeutic relationship at play. He considers the limited data available and has warned against resolutely assuming either a pro- or anti-NSC stance. He postulates that NSCs might have the best chance at saving a life in the context of ongoing therapy with a patient with mature defenses, while in other contexts, such as with a patient with borderline personality disorder, it might prove counterproductive. Importantly, he wrote, “there is not a shred of empirical evidence that safety contracting has not been a deterrent with specific clients in the hands of specific clinicians.”

Dr. Shea describes various ways of maximizing the utility of the NSC. First, he describes that NSCs may be more effective as safety assessment tools (paying attention to both verbal and nonverbal cues) than tools to directly deter attempts. Second, NSCs may have increased utility when repeated across time to provide an understanding for how the patient typically engages in contracting. Soliciting a patient’s reasons for living also can enhance a contract’s usefulness because patients with suicidal ideation weigh reasons for living against reasons for dying in their decision-making. Finally, the sound documentation of the process of contracting not only protects against subsequent legal action but also improves the quality of the clinical care, in part by entraining the psychiatrist to incorporate key elements into the contracting process.

Returning to the clinical case, the strengths and weakness of that NSC can now be evaluated. Looking at the NSC through the eyes of Dr. Shea, the young therapeutic relationship diminishes the value of the NSC, while the relationship’s ongoing basis and the patient’s mature defenses bolster it. Dr. Shea would encourage the psychiatrist to use the NSC as an assessment tool, including assessment of ambivalence. In this case, the patient’s ambivalence about suicide comes through, but it could have been explored and expanded through explicit discussion of reasons for living. Applying the lens of Dr. Linehan, the contract is strengthened by the attention paid to social supports, while it would have been improved by specific discussion about warning signs and self-management tools.

In line with Dr. Drye’s original vision of the NSC, the degree to which the patient owns the NSC seems to be particularly crucial. In this case, the patient’s ownership of the no-suicide decision was suggested by his transparency during interview and full engagement in contracting, including identification of crisis resources. Still, the patient could have been encouraged to take additional responsibility for the NSC. One means of transferring responsibility to the patient could have been giving the patient a pen to create a written record of the contract, mobilizing and symbolizing the patient’s greater control of the process and outcome. Finally, and of utmost importance, it should be reiterated that the NSC should be only part of the assessment and planning that a psychiatrist does with a suicidal patient. While there are circumstances and strategies that augment its utility, it should not be overly relied on.
 

References

1. Weiss A. Am J Psychother. 2001;55(3):414-9.

2. Kroll J. Am J Psychiatry. 2000;157(10):1684-6.

3. Shea SC. The Practical Art of Suicide Assessment: A Guide for Mental Health Professionals and Substance Abuse Counselors. Hoboken, N.J.: John Wiley & Sons, 2011.

4. Jacobs DG et al. Practice guideline for the assessment and treatment of patients with suicidal behavior. American Psychiatric Association, 2003 Nov.

5. Lewis LM. Suicide Life Threat Behav. 2007;37(1):50-7.

6. Goin M. Psychiatr News. 2003 Jul 18;38(14):3-38.

7. Drye RC et al. Am J Psychiatry. 1973;130(2):171-4.

8. Farrow TL. J Psychiatr Ment Health Nurs. 2003 Apr;10(2):199-202.

9. Miller MC et al. Harv Rev Psychiatry. 1998;6(2):78-87.

10. Bryan CJ et al. J Affect Disord. 2017 Apr;212:64-72.

11. Pederson LD. Dialectical Behavior Therapy: A Contemporary Guide for Practitioners. Hoboken, N.J.: John Wiley & Sons, 2015.
 

Dr. Roberts is a board-certified psychiatrist in Northern Virginia, working in both the partial hospital and outpatient settings. She has a special interest in working with patients with serious mental illness and believes in the recovery model of care, in which each patient’s life goals become the focal point of their treatment. Dr. Roberts completed her psychiatry residency at George Washington University, in Washington, where she also served as the 2018-2019 chief outpatient resident. She is a native of Minnesota and earned her medical degree from the University of Minnesota, Minneapolis, in 2015. Dr. Roberts has no disclosures.




 

An elderly, retired, married African American man sought psychiatric treatment for depression and suicidal thoughts. He had a detailed, lethal suicide plan, but he had not taken any steps to carry it out.

He met DSM-5 criteria for a major depressive episode, and he described a lifelong history of recurrent depressions as well as hypomanic episodes. He was diagnosed with bipolar II disorder, and he began weekly therapy, as well as medication. Despite several static and dynamic suicide risk factors, the psychiatrist also noted that he was help seeking and future oriented. He seemed transparent during his initial appointments. He did not have access to lethal means and welcomed the psychiatrist to communicate openly with his spouse.

The patient had never attempted suicide, there was no family history of suicide, and there was no psychosis or substance use disorder present. He was able to commit to reaching out to the psychiatrist, his spouse, or emergency personnel in the case of worsening suicidal thoughts or imminent suicidal action. He remained in the outpatient setting. His suicidal ideation faded and depression receded as psychotherapy and pharmacotherapy continued.

Discussion

Depression and suicidal ideation are ubiquitous in the practice of psychiatry. Psychiatrists draw from an array of assessment and management tools when this common clinical challenge arises. Among these tools is the no-suicide contract (NSC). The NSC goes by many names, including the no-harm contract and suicide prevention contract.¹ It is a promise, verbal or written, from the patient to not attempt suicide and to tell a loved one or psychiatric provider instead.² The verbal exchange between the patient and therapist described in the case fits the widely accepted clinical definition of an NSC. The contents and implementation of NSCs vary greatly; no standard approach is taught in psychiatric training.³ The American Psychiatric Association has warned against over-reliance on them, emphasizing that they have not been proven effective. It advises that NSCs should not be used independently of other tools or outside well-established patient-provider relationships.⁴ A 2007 review of the literature on NSCs concluded that there were no data to support their effectiveness and some data that they might even cause harm.⁵

The origin of the NSC

The NSC is fairly young and its foundation arguably weak. Its evolution has been traced back to a study published in 1973 by Robert C. Drye, MD, and associates on the effectiveness of a questionnaire for the assessment of suicide risk.⁶ The questionnaire centered on the patient’s reaction to the statement, “No matter what happens, I will not kill myself, accidently or on purpose, at any time.” The authors placed special emphasis on the words “I will,” which they felt to be a stronger indicator of commitment to safety than “I promise.” The authors thought the latter statement sounded like a child’s empty reply to a demanding parent. The authors reported a 100% success rate with “approximately 600 patients” across geographic regions and clinical settings.⁷ The study group is not further described, and that the authors contend that the intervention had “complete effectiveness in evaluating suicide risk” should give pause to anyone aiming to practice evidence-based psychiatry.

The theoretical basis of the NSC has been presumed by others to be based, in part, on the principles of transactional analysis. Specifically, the suicidal patient is seen as occupying the child ego state, and the NSC is seen as a means of moving the patient into the less problematic adult ego state. It has been argued, however, that an NSC can achieve exactly the opposite. The contract can pit the patient against the clinician, entrenching the patient deeper into the child ego and, therefore, suicidal state.⁸

Michael Craig Miller, MD, and associates proposed other psychological reasons why NSCs may be counterproductive. They write, “Psychological pitfalls abound, and any of them may contribute to a contract being thoughtless, unrealistic, irrelevant, cynical, punitive, or coercive.”⁹ They postulated that the NSC grew out of and assumes the same shared decision-making inherent in any therapeutic contract – and they argue that this assumption is flawed given the legal power clinicians have over suicidal patients. While acknowledging this problematic power differential, the authors go on to urge clinicians to aim for shared decision-making and a shared burden of risk when discussing treatment with suicidal patients.

Possible NSC common factors

Psychiatry, like the rest of medicine, is increasingly practiced in an evidence-based manner. The NSC should not be excluded from this movement. To this end, a recently published, randomized study of 97 active duty Army personnel seeking emergency behavioral health evaluation compared the effectiveness of NSCs and with an alternative intervention, the crisis response plan (CRP). The CRP was chosen because it had been suggested by the Joint Commision as an alternative to the NSC, although it also has little evidence supporting its use.¹⁰

The NSC and CRP interventions of the Army study were very similar. Both included suicide risk assessment, supportive listening, provision of crisis resources, and referral to treatment. In addition, the NSC intervention included asking whether the patients could keep themselves safe at home. The CRP intervention included collaboration with the patient to identify warning signs of crisis, self-management skills, and support persons. A seemingly small but interesting difference between the two interventions was which member of the dyad, patient or clinician, created a written record of the discussion. In the NSC group, the assessor did the writing, while in the CRP group, the patient controlled the pen.

The results of the study were intriguing. Suicidal ideation declined faster in the CRP arm. Participants in the CRP arm were 76% less likely to attempt suicide over 6 months, although this effect decreased and lost statistical significance when controlling for baseline severity of suicidal ideation. Despite those promising data, the only completed suicide was in the CRP arm.

The authors compared the makeup of the CRP intervention with key components of dialectical behavior therapy (DBT). They pointed to a 2015 study by Marsha Linehan, PhD, and associates that sought to identify the active ingredients of DBT. The Linehan study indicated that attending to warning signs and using self-management tools and social supports contributed more to the success of DBT than the individual therapy component. Interestingly, these were the same features that set the CRP intervention apart from the NSC in the Army study. Perhaps these are the common factors of effective counseling of suicidal patients.

Indeed, these factors seem to harken back to the NSC as originally envisioned by the late Dr. Drye – a patient-driven collaboration. Dr. Drye and associates wrote: “This approach developed out of our belief that the only therapeutic contracts likely to lead to change are those developed by the patient himself, for which he will assume responsibility.” While the data presented by Dr. Drye and associates were weak, the theory behind their NSC – patient commitment – seems solid. Commitment strategies, which grew out of social psychology, are effective and heavily used in DBT, including to decrease suicidal behaviors.¹¹

Conclusion

Suicidologist Shawn Christopher Shea, MD, argues that the answer to whether or not NSCs can work is conditional on the unique combination of patient, clinician, and therapeutic relationship at play. He considers the limited data available and has warned against resolutely assuming either a pro- or anti-NSC stance. He postulates that NSCs might have the best chance at saving a life in the context of ongoing therapy with a patient with mature defenses, while in other contexts, such as with a patient with borderline personality disorder, it might prove counterproductive. Importantly, he wrote, “there is not a shred of empirical evidence that safety contracting has not been a deterrent with specific clients in the hands of specific clinicians.”

Dr. Shea describes various ways of maximizing the utility of the NSC. First, he describes that NSCs may be more effective as safety assessment tools (paying attention to both verbal and nonverbal cues) than tools to directly deter attempts. Second, NSCs may have increased utility when repeated across time to provide an understanding for how the patient typically engages in contracting. Soliciting a patient’s reasons for living also can enhance a contract’s usefulness because patients with suicidal ideation weigh reasons for living against reasons for dying in their decision-making. Finally, the sound documentation of the process of contracting not only protects against subsequent legal action but also improves the quality of the clinical care, in part by entraining the psychiatrist to incorporate key elements into the contracting process.

Returning to the clinical case, the strengths and weakness of that NSC can now be evaluated. Looking at the NSC through the eyes of Dr. Shea, the young therapeutic relationship diminishes the value of the NSC, while the relationship’s ongoing basis and the patient’s mature defenses bolster it. Dr. Shea would encourage the psychiatrist to use the NSC as an assessment tool, including assessment of ambivalence. In this case, the patient’s ambivalence about suicide comes through, but it could have been explored and expanded through explicit discussion of reasons for living. Applying the lens of Dr. Linehan, the contract is strengthened by the attention paid to social supports, while it would have been improved by specific discussion about warning signs and self-management tools.

In line with Dr. Drye’s original vision of the NSC, the degree to which the patient owns the NSC seems to be particularly crucial. In this case, the patient’s ownership of the no-suicide decision was suggested by his transparency during interview and full engagement in contracting, including identification of crisis resources. Still, the patient could have been encouraged to take additional responsibility for the NSC. One means of transferring responsibility to the patient could have been giving the patient a pen to create a written record of the contract, mobilizing and symbolizing the patient’s greater control of the process and outcome. Finally, and of utmost importance, it should be reiterated that the NSC should be only part of the assessment and planning that a psychiatrist does with a suicidal patient. While there are circumstances and strategies that augment its utility, it should not be overly relied on.
 

References

1. Weiss A. Am J Psychother. 2001;55(3):414-9.

2. Kroll J. Am J Psychiatry. 2000;157(10):1684-6.

3. Shea SC. The Practical Art of Suicide Assessment: A Guide for Mental Health Professionals and Substance Abuse Counselors. Hoboken, N.J.: John Wiley & Sons, 2011.

4. Jacobs DG et al. Practice guideline for the assessment and treatment of patients with suicidal behavior. American Psychiatric Association, 2003 Nov.

5. Lewis LM. Suicide Life Threat Behav. 2007;37(1):50-7.

6. Goin M. Psychiatr News. 2003 Jul 18;38(14):3-38.

7. Drye RC et al. Am J Psychiatry. 1973;130(2):171-4.

8. Farrow TL. J Psychiatr Ment Health Nurs. 2003 Apr;10(2):199-202.

9. Miller MC et al. Harv Rev Psychiatry. 1998;6(2):78-87.

10. Bryan CJ et al. J Affect Disord. 2017 Apr;212:64-72.

11. Pederson LD. Dialectical Behavior Therapy: A Contemporary Guide for Practitioners. Hoboken, N.J.: John Wiley & Sons, 2015.
 

Dr. Roberts is a board-certified psychiatrist in Northern Virginia, working in both the partial hospital and outpatient settings. She has a special interest in working with patients with serious mental illness and believes in the recovery model of care, in which each patient’s life goals become the focal point of their treatment. Dr. Roberts completed her psychiatry residency at George Washington University, in Washington, where she also served as the 2018-2019 chief outpatient resident. She is a native of Minnesota and earned her medical degree from the University of Minnesota, Minneapolis, in 2015. Dr. Roberts has no disclosures.




 

An elderly, retired, married African American man sought psychiatric treatment for depression and suicidal thoughts. He had a detailed, lethal suicide plan, but he had not taken any steps to carry it out.

He met DSM-5 criteria for a major depressive episode, and he described a lifelong history of recurrent depressions as well as hypomanic episodes. He was diagnosed with bipolar II disorder, and he began weekly therapy, as well as medication. Despite several static and dynamic suicide risk factors, the psychiatrist also noted that he was help seeking and future oriented. He seemed transparent during his initial appointments. He did not have access to lethal means and welcomed the psychiatrist to communicate openly with his spouse.

The patient had never attempted suicide, there was no family history of suicide, and there was no psychosis or substance use disorder present. He was able to commit to reaching out to the psychiatrist, his spouse, or emergency personnel in the case of worsening suicidal thoughts or imminent suicidal action. He remained in the outpatient setting. His suicidal ideation faded and depression receded as psychotherapy and pharmacotherapy continued.

Discussion

Depression and suicidal ideation are ubiquitous in the practice of psychiatry. Psychiatrists draw from an array of assessment and management tools when this common clinical challenge arises. Among these tools is the no-suicide contract (NSC). The NSC goes by many names, including the no-harm contract and suicide prevention contract.¹ It is a promise, verbal or written, from the patient to not attempt suicide and to tell a loved one or psychiatric provider instead.² The verbal exchange between the patient and therapist described in the case fits the widely accepted clinical definition of an NSC. The contents and implementation of NSCs vary greatly; no standard approach is taught in psychiatric training.³ The American Psychiatric Association has warned against over-reliance on them, emphasizing that they have not been proven effective. It advises that NSCs should not be used independently of other tools or outside well-established patient-provider relationships.⁴ A 2007 review of the literature on NSCs concluded that there were no data to support their effectiveness and some data that they might even cause harm.⁵

The origin of the NSC

The NSC is fairly young and its foundation arguably weak. Its evolution has been traced back to a study published in 1973 by Robert C. Drye, MD, and associates on the effectiveness of a questionnaire for the assessment of suicide risk.⁶ The questionnaire centered on the patient’s reaction to the statement, “No matter what happens, I will not kill myself, accidently or on purpose, at any time.” The authors placed special emphasis on the words “I will,” which they felt to be a stronger indicator of commitment to safety than “I promise.” The authors thought the latter statement sounded like a child’s empty reply to a demanding parent. The authors reported a 100% success rate with “approximately 600 patients” across geographic regions and clinical settings.⁷ The study group is not further described, and that the authors contend that the intervention had “complete effectiveness in evaluating suicide risk” should give pause to anyone aiming to practice evidence-based psychiatry.

The theoretical basis of the NSC has been presumed by others to be based, in part, on the principles of transactional analysis. Specifically, the suicidal patient is seen as occupying the child ego state, and the NSC is seen as a means of moving the patient into the less problematic adult ego state. It has been argued, however, that an NSC can achieve exactly the opposite. The contract can pit the patient against the clinician, entrenching the patient deeper into the child ego and, therefore, suicidal state.⁸

Michael Craig Miller, MD, and associates proposed other psychological reasons why NSCs may be counterproductive. They write, “Psychological pitfalls abound, and any of them may contribute to a contract being thoughtless, unrealistic, irrelevant, cynical, punitive, or coercive.”⁹ They postulated that the NSC grew out of and assumes the same shared decision-making inherent in any therapeutic contract – and they argue that this assumption is flawed given the legal power clinicians have over suicidal patients. While acknowledging this problematic power differential, the authors go on to urge clinicians to aim for shared decision-making and a shared burden of risk when discussing treatment with suicidal patients.

Possible NSC common factors

Psychiatry, like the rest of medicine, is increasingly practiced in an evidence-based manner. The NSC should not be excluded from this movement. To this end, a recently published, randomized study of 97 active duty Army personnel seeking emergency behavioral health evaluation compared the effectiveness of NSCs and with an alternative intervention, the crisis response plan (CRP). The CRP was chosen because it had been suggested by the Joint Commision as an alternative to the NSC, although it also has little evidence supporting its use.¹⁰

The NSC and CRP interventions of the Army study were very similar. Both included suicide risk assessment, supportive listening, provision of crisis resources, and referral to treatment. In addition, the NSC intervention included asking whether the patients could keep themselves safe at home. The CRP intervention included collaboration with the patient to identify warning signs of crisis, self-management skills, and support persons. A seemingly small but interesting difference between the two interventions was which member of the dyad, patient or clinician, created a written record of the discussion. In the NSC group, the assessor did the writing, while in the CRP group, the patient controlled the pen.

The results of the study were intriguing. Suicidal ideation declined faster in the CRP arm. Participants in the CRP arm were 76% less likely to attempt suicide over 6 months, although this effect decreased and lost statistical significance when controlling for baseline severity of suicidal ideation. Despite those promising data, the only completed suicide was in the CRP arm.

The authors compared the makeup of the CRP intervention with key components of dialectical behavior therapy (DBT). They pointed to a 2015 study by Marsha Linehan, PhD, and associates that sought to identify the active ingredients of DBT. The Linehan study indicated that attending to warning signs and using self-management tools and social supports contributed more to the success of DBT than the individual therapy component. Interestingly, these were the same features that set the CRP intervention apart from the NSC in the Army study. Perhaps these are the common factors of effective counseling of suicidal patients.

Indeed, these factors seem to harken back to the NSC as originally envisioned by the late Dr. Drye – a patient-driven collaboration. Dr. Drye and associates wrote: “This approach developed out of our belief that the only therapeutic contracts likely to lead to change are those developed by the patient himself, for which he will assume responsibility.” While the data presented by Dr. Drye and associates were weak, the theory behind their NSC – patient commitment – seems solid. Commitment strategies, which grew out of social psychology, are effective and heavily used in DBT, including to decrease suicidal behaviors.¹¹

Conclusion

Suicidologist Shawn Christopher Shea, MD, argues that the answer to whether or not NSCs can work is conditional on the unique combination of patient, clinician, and therapeutic relationship at play. He considers the limited data available and has warned against resolutely assuming either a pro- or anti-NSC stance. He postulates that NSCs might have the best chance at saving a life in the context of ongoing therapy with a patient with mature defenses, while in other contexts, such as with a patient with borderline personality disorder, it might prove counterproductive. Importantly, he wrote, “there is not a shred of empirical evidence that safety contracting has not been a deterrent with specific clients in the hands of specific clinicians.”

Dr. Shea describes various ways of maximizing the utility of the NSC. First, he describes that NSCs may be more effective as safety assessment tools (paying attention to both verbal and nonverbal cues) than tools to directly deter attempts. Second, NSCs may have increased utility when repeated across time to provide an understanding for how the patient typically engages in contracting. Soliciting a patient’s reasons for living also can enhance a contract’s usefulness because patients with suicidal ideation weigh reasons for living against reasons for dying in their decision-making. Finally, the sound documentation of the process of contracting not only protects against subsequent legal action but also improves the quality of the clinical care, in part by entraining the psychiatrist to incorporate key elements into the contracting process.

Returning to the clinical case, the strengths and weakness of that NSC can now be evaluated. Looking at the NSC through the eyes of Dr. Shea, the young therapeutic relationship diminishes the value of the NSC, while the relationship’s ongoing basis and the patient’s mature defenses bolster it. Dr. Shea would encourage the psychiatrist to use the NSC as an assessment tool, including assessment of ambivalence. In this case, the patient’s ambivalence about suicide comes through, but it could have been explored and expanded through explicit discussion of reasons for living. Applying the lens of Dr. Linehan, the contract is strengthened by the attention paid to social supports, while it would have been improved by specific discussion about warning signs and self-management tools.

In line with Dr. Drye’s original vision of the NSC, the degree to which the patient owns the NSC seems to be particularly crucial. In this case, the patient’s ownership of the no-suicide decision was suggested by his transparency during interview and full engagement in contracting, including identification of crisis resources. Still, the patient could have been encouraged to take additional responsibility for the NSC. One means of transferring responsibility to the patient could have been giving the patient a pen to create a written record of the contract, mobilizing and symbolizing the patient’s greater control of the process and outcome. Finally, and of utmost importance, it should be reiterated that the NSC should be only part of the assessment and planning that a psychiatrist does with a suicidal patient. While there are circumstances and strategies that augment its utility, it should not be overly relied on.
 

References

1. Weiss A. Am J Psychother. 2001;55(3):414-9.

2. Kroll J. Am J Psychiatry. 2000;157(10):1684-6.

3. Shea SC. The Practical Art of Suicide Assessment: A Guide for Mental Health Professionals and Substance Abuse Counselors. Hoboken, N.J.: John Wiley & Sons, 2011.

4. Jacobs DG et al. Practice guideline for the assessment and treatment of patients with suicidal behavior. American Psychiatric Association, 2003 Nov.

5. Lewis LM. Suicide Life Threat Behav. 2007;37(1):50-7.

6. Goin M. Psychiatr News. 2003 Jul 18;38(14):3-38.

7. Drye RC et al. Am J Psychiatry. 1973;130(2):171-4.

8. Farrow TL. J Psychiatr Ment Health Nurs. 2003 Apr;10(2):199-202.

9. Miller MC et al. Harv Rev Psychiatry. 1998;6(2):78-87.

10. Bryan CJ et al. J Affect Disord. 2017 Apr;212:64-72.

11. Pederson LD. Dialectical Behavior Therapy: A Contemporary Guide for Practitioners. Hoboken, N.J.: John Wiley & Sons, 2015.
 

Dr. Roberts is a board-certified psychiatrist in Northern Virginia, working in both the partial hospital and outpatient settings. She has a special interest in working with patients with serious mental illness and believes in the recovery model of care, in which each patient’s life goals become the focal point of their treatment. Dr. Roberts completed her psychiatry residency at George Washington University, in Washington, where she also served as the 2018-2019 chief outpatient resident. She is a native of Minnesota and earned her medical degree from the University of Minnesota, Minneapolis, in 2015. Dr. Roberts has no disclosures.




 

For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.

However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.

Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
 

Limited, old evidence

The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”

They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.

Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.

Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).

Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.

However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
 

Psychotic depression markers?

For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.

Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.

Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.

Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.

“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.

The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.

They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.

“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”

She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
 

Confirmatory data

Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”

However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.

Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.

“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”

As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”

Many things that ECT “corrects” are disturbed in psychotic depression, including cortisol homeostasis, which is thought to be affected via the hypothalamic-pituitary-adrenal axis, Petrides added.

That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.

One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.

He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.

The study authors and Petrides have reported no relevant financial relationships.

This article first appeared on Medscape.com.

For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.

However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.

Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
 

Limited, old evidence

The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”

They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.

Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.

Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).

Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.

However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
 

Psychotic depression markers?

For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.

Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.

Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.

Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.

“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.

The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.

They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.

“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”

She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
 

Confirmatory data

Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”

However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.

Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.

“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”

As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”

Many things that ECT “corrects” are disturbed in psychotic depression, including cortisol homeostasis, which is thought to be affected via the hypothalamic-pituitary-adrenal axis, Petrides added.

That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.

One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.

He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.

The study authors and Petrides have reported no relevant financial relationships.

This article first appeared on Medscape.com.

For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.

However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.

Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
 

Limited, old evidence

The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”

They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.

Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.

Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).

Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.

However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
 

Psychotic depression markers?

For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.

Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.

Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.

Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.

“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.

The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.

They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.

“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”

She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
 

Confirmatory data

Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”

However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.

Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.

“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”

As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”

Many things that ECT “corrects” are disturbed in psychotic depression, including cortisol homeostasis, which is thought to be affected via the hypothalamic-pituitary-adrenal axis, Petrides added.

That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.

One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.

He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.

The study authors and Petrides have reported no relevant financial relationships.

This article first appeared on Medscape.com.