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Expert: Engage patients, clinicians as partners in research
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
EXPERT ANALYSIS FROM THE ASCP ANNUAL MEETING
VA/DOD elevate psychotherapy over medication in updated PTSD guidelines
MIAMI – New federal clinical practice guidelines for treating posttraumatic stress disorder move trauma-focused psychotherapy ahead of pharmacotherapy as first-line treatment.
“That is quite a statement that is being made, and it’s a big shift in our treatment guidelines,” Lori L. Davis, MD, said at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. Dr. Davis, who coauthored the update for the Departments of Veterans Affairs and of Defense, discussed the guidelines at the meeting in advance of their release this summer.
The guidelines, dated June 2017 and based on evidence reviewed through March 2016, specify that evidence is strong for first-line psychotherapy that includes some form of exposure and/or cognitive restructuring. Such therapies include prolonged exposure, cognitive processing, eye movement desensitization and reprocessing, narrative exposure therapy, brief eclectic psychotherapy, and PTSD-specific cognitive-behavioral therapy.
The Management of Posttraumatic Stress Work Group found that evidence was weakest for non–trauma-focused therapies, such as stress inoculation training and present-centered and interpersonal psychotherapy. Manualized group therapy also was rated as weak, but insufficient evidence was found to rate one type of group therapy over another.
Insufficient evidence also was cited for psychotherapies not specified in other recommendations, such as dialectical behavior therapy, skills training in affect and interpersonal regulation, acceptance and commitment therapy (ACT), seeking safety therapy, or supportive counseling.
“Some of these treatments have been found to be effective for the treatment of other disorders (e.g., ACT for [major depressive disorder]),” the work group members wrote, “but do not have evidence of efficacy in patients with PTSD.”
The recommendations are based on a review of literature from the past 20 years and are congruent with other treatment guidelines internationally, according to Sheila A.M. Rausch, PhD, who directs mental health research and program evaluation for the VA Ann Arbor Healthcare System in Michigan, is a work group member, and served as a panelist at the meeting.
“What is striking is that, based on people reviewing all the evidence out there – and there are different methodologies for doing so – regardless, [the different groups] tend to come to the same conclusions,” Dr. Rausch said.
The updated guidelines cite insufficient evidence for making any recommendations for augmented or combined treatments of psychotherapy and pharmacotherapy.
Medications considered to have a strong evidence base for monotherapy were sertraline, paroxetine, fluoxetine, and venlafaxine. In cases in which a person declines psychotherapy, those medications are recommended as first-line treatment.
Prazosin, typically used to managing nightmares tied to PTSD, received a “suggest against” recommendation, in part because of the discovery of a publication bias, according to Dr. Davis, who is associate chief of staff for research and development at the Tuscaloosa (Ala.) VA Medical Center and a clinical professor of psychiatry and behavioral neurobiology at the University of Alabama in Birmingham and Tuscaloosa. She noted that the work group remained unsure of “how to grapple with this” news that the study drug did not break from placebo in the treatment of nightmares in more than 300 combat veterans with PTSD.
“We are not trying to tell you not to use antidepressants for major depressive disorder or panic disorders that are often comorbid with PTSD, so you have to keep that in mind as you read these guidelines,” Dr. Davis said. Many patients already take antidepressants because they are easily accessed in primary care practices, she added.
The work group found that evidence generally was weak against atypical antipsychotics – particularly in light of the known adverse side effects of those drugs. However, the group singled out risperidone. “We suggest against treatment of PTSD with quetiapine, olanzapine, and other atypical antipsychotics (except for risperidone, which is a ‘strong against,’ see recommendation 20),” the guidelines suggest.
They also “suggested against” two antidepressants – citalopram and amitriptyline, a tricyclic. The quality of evidence for those drugs was deemed low. Two drugs – lamotrigine and topiramate – also received “suggested against” rankings, and the evidence for the use of those drugs was deemed very low.
Meanwhile, the work group wrote that the quality of evidence was low and “recommended against” the use of three other drugs: divalproex, tiagabine, and guanfacine. They also found the quality of evidence to be very low for the drug class of benzodiazepines and four drugs – risperidone, D-cycloserine, ketamine, and hydrocortisone. They also found insufficient evidence to recommend complementary and integrative health (CIH) practices such as meditation and yoga for treating PTSD. The work group did offer a caveat, however. “It is important to clarify that we are not recommending against the treatments but rather are saying that, at this time, the research does not support the use of any CIH practice for the primary treatment of PTSD.”
Cannabis and its derivatives also were recommended against by the work group because of a “lack of evidence for their efficacy, known adverse effects, and associated risks.”
Dr. Davis said the work group’s findings underscored a crisis in pharmacotherapeutic research in PTSD. Since 2006, there have been only four industry-sponsored drugs for PTSD. “I find it kind of sad,” she said.
Currently, Dr. Rausch’s own study for the VA focuses on comparing the effects of combination therapies for PTSD in the context of patient preferences, in order to tailor the treatments accordingly. In 223 returning veterans with PTSD, she and her colleagues are conducting a head-to-head comparison of prolonged exposure therapy plus placebo, prolonged exposure plus sertraline, and sertraline plus emotion memory management therapy to determine how starting a patient on both kinds of treatments simultaneously affect response.
“It’s clinically important to find out what is really going on in the brain and body,” she said. “Although we know we have therapies that work, we need to find answers for partial responders ... and how to increase the speed and magnitude of response.”
Dr. Davis’s research is funded in part by the VA, Forest, Merck, Tonix, and Otsuka, for whom she also acts as a consultant. Dr. Rausch did not have any disclosures.
MIAMI – New federal clinical practice guidelines for treating posttraumatic stress disorder move trauma-focused psychotherapy ahead of pharmacotherapy as first-line treatment.
“That is quite a statement that is being made, and it’s a big shift in our treatment guidelines,” Lori L. Davis, MD, said at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. Dr. Davis, who coauthored the update for the Departments of Veterans Affairs and of Defense, discussed the guidelines at the meeting in advance of their release this summer.
The guidelines, dated June 2017 and based on evidence reviewed through March 2016, specify that evidence is strong for first-line psychotherapy that includes some form of exposure and/or cognitive restructuring. Such therapies include prolonged exposure, cognitive processing, eye movement desensitization and reprocessing, narrative exposure therapy, brief eclectic psychotherapy, and PTSD-specific cognitive-behavioral therapy.
The Management of Posttraumatic Stress Work Group found that evidence was weakest for non–trauma-focused therapies, such as stress inoculation training and present-centered and interpersonal psychotherapy. Manualized group therapy also was rated as weak, but insufficient evidence was found to rate one type of group therapy over another.
Insufficient evidence also was cited for psychotherapies not specified in other recommendations, such as dialectical behavior therapy, skills training in affect and interpersonal regulation, acceptance and commitment therapy (ACT), seeking safety therapy, or supportive counseling.
“Some of these treatments have been found to be effective for the treatment of other disorders (e.g., ACT for [major depressive disorder]),” the work group members wrote, “but do not have evidence of efficacy in patients with PTSD.”
The recommendations are based on a review of literature from the past 20 years and are congruent with other treatment guidelines internationally, according to Sheila A.M. Rausch, PhD, who directs mental health research and program evaluation for the VA Ann Arbor Healthcare System in Michigan, is a work group member, and served as a panelist at the meeting.
“What is striking is that, based on people reviewing all the evidence out there – and there are different methodologies for doing so – regardless, [the different groups] tend to come to the same conclusions,” Dr. Rausch said.
The updated guidelines cite insufficient evidence for making any recommendations for augmented or combined treatments of psychotherapy and pharmacotherapy.
Medications considered to have a strong evidence base for monotherapy were sertraline, paroxetine, fluoxetine, and venlafaxine. In cases in which a person declines psychotherapy, those medications are recommended as first-line treatment.
Prazosin, typically used to managing nightmares tied to PTSD, received a “suggest against” recommendation, in part because of the discovery of a publication bias, according to Dr. Davis, who is associate chief of staff for research and development at the Tuscaloosa (Ala.) VA Medical Center and a clinical professor of psychiatry and behavioral neurobiology at the University of Alabama in Birmingham and Tuscaloosa. She noted that the work group remained unsure of “how to grapple with this” news that the study drug did not break from placebo in the treatment of nightmares in more than 300 combat veterans with PTSD.
“We are not trying to tell you not to use antidepressants for major depressive disorder or panic disorders that are often comorbid with PTSD, so you have to keep that in mind as you read these guidelines,” Dr. Davis said. Many patients already take antidepressants because they are easily accessed in primary care practices, she added.
The work group found that evidence generally was weak against atypical antipsychotics – particularly in light of the known adverse side effects of those drugs. However, the group singled out risperidone. “We suggest against treatment of PTSD with quetiapine, olanzapine, and other atypical antipsychotics (except for risperidone, which is a ‘strong against,’ see recommendation 20),” the guidelines suggest.
They also “suggested against” two antidepressants – citalopram and amitriptyline, a tricyclic. The quality of evidence for those drugs was deemed low. Two drugs – lamotrigine and topiramate – also received “suggested against” rankings, and the evidence for the use of those drugs was deemed very low.
Meanwhile, the work group wrote that the quality of evidence was low and “recommended against” the use of three other drugs: divalproex, tiagabine, and guanfacine. They also found the quality of evidence to be very low for the drug class of benzodiazepines and four drugs – risperidone, D-cycloserine, ketamine, and hydrocortisone. They also found insufficient evidence to recommend complementary and integrative health (CIH) practices such as meditation and yoga for treating PTSD. The work group did offer a caveat, however. “It is important to clarify that we are not recommending against the treatments but rather are saying that, at this time, the research does not support the use of any CIH practice for the primary treatment of PTSD.”
Cannabis and its derivatives also were recommended against by the work group because of a “lack of evidence for their efficacy, known adverse effects, and associated risks.”
Dr. Davis said the work group’s findings underscored a crisis in pharmacotherapeutic research in PTSD. Since 2006, there have been only four industry-sponsored drugs for PTSD. “I find it kind of sad,” she said.
Currently, Dr. Rausch’s own study for the VA focuses on comparing the effects of combination therapies for PTSD in the context of patient preferences, in order to tailor the treatments accordingly. In 223 returning veterans with PTSD, she and her colleagues are conducting a head-to-head comparison of prolonged exposure therapy plus placebo, prolonged exposure plus sertraline, and sertraline plus emotion memory management therapy to determine how starting a patient on both kinds of treatments simultaneously affect response.
“It’s clinically important to find out what is really going on in the brain and body,” she said. “Although we know we have therapies that work, we need to find answers for partial responders ... and how to increase the speed and magnitude of response.”
Dr. Davis’s research is funded in part by the VA, Forest, Merck, Tonix, and Otsuka, for whom she also acts as a consultant. Dr. Rausch did not have any disclosures.
MIAMI – New federal clinical practice guidelines for treating posttraumatic stress disorder move trauma-focused psychotherapy ahead of pharmacotherapy as first-line treatment.
“That is quite a statement that is being made, and it’s a big shift in our treatment guidelines,” Lori L. Davis, MD, said at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. Dr. Davis, who coauthored the update for the Departments of Veterans Affairs and of Defense, discussed the guidelines at the meeting in advance of their release this summer.
The guidelines, dated June 2017 and based on evidence reviewed through March 2016, specify that evidence is strong for first-line psychotherapy that includes some form of exposure and/or cognitive restructuring. Such therapies include prolonged exposure, cognitive processing, eye movement desensitization and reprocessing, narrative exposure therapy, brief eclectic psychotherapy, and PTSD-specific cognitive-behavioral therapy.
The Management of Posttraumatic Stress Work Group found that evidence was weakest for non–trauma-focused therapies, such as stress inoculation training and present-centered and interpersonal psychotherapy. Manualized group therapy also was rated as weak, but insufficient evidence was found to rate one type of group therapy over another.
Insufficient evidence also was cited for psychotherapies not specified in other recommendations, such as dialectical behavior therapy, skills training in affect and interpersonal regulation, acceptance and commitment therapy (ACT), seeking safety therapy, or supportive counseling.
“Some of these treatments have been found to be effective for the treatment of other disorders (e.g., ACT for [major depressive disorder]),” the work group members wrote, “but do not have evidence of efficacy in patients with PTSD.”
The recommendations are based on a review of literature from the past 20 years and are congruent with other treatment guidelines internationally, according to Sheila A.M. Rausch, PhD, who directs mental health research and program evaluation for the VA Ann Arbor Healthcare System in Michigan, is a work group member, and served as a panelist at the meeting.
“What is striking is that, based on people reviewing all the evidence out there – and there are different methodologies for doing so – regardless, [the different groups] tend to come to the same conclusions,” Dr. Rausch said.
The updated guidelines cite insufficient evidence for making any recommendations for augmented or combined treatments of psychotherapy and pharmacotherapy.
Medications considered to have a strong evidence base for monotherapy were sertraline, paroxetine, fluoxetine, and venlafaxine. In cases in which a person declines psychotherapy, those medications are recommended as first-line treatment.
Prazosin, typically used to managing nightmares tied to PTSD, received a “suggest against” recommendation, in part because of the discovery of a publication bias, according to Dr. Davis, who is associate chief of staff for research and development at the Tuscaloosa (Ala.) VA Medical Center and a clinical professor of psychiatry and behavioral neurobiology at the University of Alabama in Birmingham and Tuscaloosa. She noted that the work group remained unsure of “how to grapple with this” news that the study drug did not break from placebo in the treatment of nightmares in more than 300 combat veterans with PTSD.
“We are not trying to tell you not to use antidepressants for major depressive disorder or panic disorders that are often comorbid with PTSD, so you have to keep that in mind as you read these guidelines,” Dr. Davis said. Many patients already take antidepressants because they are easily accessed in primary care practices, she added.
The work group found that evidence generally was weak against atypical antipsychotics – particularly in light of the known adverse side effects of those drugs. However, the group singled out risperidone. “We suggest against treatment of PTSD with quetiapine, olanzapine, and other atypical antipsychotics (except for risperidone, which is a ‘strong against,’ see recommendation 20),” the guidelines suggest.
They also “suggested against” two antidepressants – citalopram and amitriptyline, a tricyclic. The quality of evidence for those drugs was deemed low. Two drugs – lamotrigine and topiramate – also received “suggested against” rankings, and the evidence for the use of those drugs was deemed very low.
Meanwhile, the work group wrote that the quality of evidence was low and “recommended against” the use of three other drugs: divalproex, tiagabine, and guanfacine. They also found the quality of evidence to be very low for the drug class of benzodiazepines and four drugs – risperidone, D-cycloserine, ketamine, and hydrocortisone. They also found insufficient evidence to recommend complementary and integrative health (CIH) practices such as meditation and yoga for treating PTSD. The work group did offer a caveat, however. “It is important to clarify that we are not recommending against the treatments but rather are saying that, at this time, the research does not support the use of any CIH practice for the primary treatment of PTSD.”
Cannabis and its derivatives also were recommended against by the work group because of a “lack of evidence for their efficacy, known adverse effects, and associated risks.”
Dr. Davis said the work group’s findings underscored a crisis in pharmacotherapeutic research in PTSD. Since 2006, there have been only four industry-sponsored drugs for PTSD. “I find it kind of sad,” she said.
Currently, Dr. Rausch’s own study for the VA focuses on comparing the effects of combination therapies for PTSD in the context of patient preferences, in order to tailor the treatments accordingly. In 223 returning veterans with PTSD, she and her colleagues are conducting a head-to-head comparison of prolonged exposure therapy plus placebo, prolonged exposure plus sertraline, and sertraline plus emotion memory management therapy to determine how starting a patient on both kinds of treatments simultaneously affect response.
“It’s clinically important to find out what is really going on in the brain and body,” she said. “Although we know we have therapies that work, we need to find answers for partial responders ... and how to increase the speed and magnitude of response.”
Dr. Davis’s research is funded in part by the VA, Forest, Merck, Tonix, and Otsuka, for whom she also acts as a consultant. Dr. Rausch did not have any disclosures.
EXPERT ANALYSIS FROM THE ASCP ANNUAL MEETING
Patients’ profile deemed best criteria for LAIs in bipolar disorder
MIAMI – Expert clinicians endorsed long-acting injectables as a preferred treatment for bipolar I disorder on the basis of patient characteristics and treatment history, rather than on an assumed level of treatment adherence, according to a small survey.
“Just over three-quarters of the experts we surveyed said they were ‘somewhat’ or ‘not very’ confident about their ability to assess their patients’ adherence,” said Martha Sajatovic, MD, who presented the data during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The finding reflects a shift, according to Dr. Sajatovic, professor of psychiatry and neurology, and the Willard Brown Chair in Neurological Outcomes Research, at Case Western University in Cleveland.
The traditional view of using long-acting injectable antipsychotics (LAIs) for patients with bipolar I disorder is that they are appropriate only in certain cohorts, such as patients with very severe illness or at the more extreme spectrum in terms of risk, and those who are homeless or pose a risk to themselves or others, Dr. Sajatovic said. Also, when it comes to the use of LAIs, there is a lack of guidance – which might contribute to clinicians’ reluctance to prescribe or recommend them, she said.
In the survey, of the 42 experts contacted by Dr. Sajatovic and her colleagues, 34 responded. According to those respondents, 11% of their patients with bipolar disorder were being treated with LAIs, compared with one-third of all patients with schizophrenia/schizoaffective disorder.
Using a scale of 1-9, with 1 being “extremely inappropriate,” 2-3 being “usually inappropriate,” 4-6 being “sometimes appropriate,” 7-8 being “usually appropriate,” and 9 being “extremely appropriate,” all tended to favor patient characteristics and treatment history over adherence when rating criteria for treatment selection. This was true regardless of whether patients were newly diagnosed with bipolar disorder, or whether their diagnosis was established and treated with an antipsychotic for 2 or more years.
For comparison, Dr. Sajatovic and her colleagues also surveyed the expert panel members on their use of LAIs in established schizophrenia and schizoaffective disorder.
Patients with a history of two or more hospitalizations for bipolar relapses and those who were either homeless or had unstable housing were rated by most respondents as usually appropriate for LAIs as first-line treatment. For those with dubious treatment adherence, the profile was similar: LAIs were considered by a majority of respondents as usually appropriate if there was a history of two or more hospitalizations for bipolar relapses, as well as homelessness or an unstable housing situation. LAIs also were considered by a majority as usually appropriate in this cohort if there was a history of violence to others, and if patients had poor insight into their illness.
Spotty treatment adherence to medications was the most common treatment history characteristic cited for first-line prescription of LAIs in patients with an established bipolar disorder diagnosis. Other first-line LAI criteria cited by most respondents for this cohort were if they previously had done well on an LAI, and if they frequently missed clinic appointments.
Virtually all the criteria above applied to patients with established illness and questionable adherence, although the expert clinicians also largely cited a failure to respond to lithium or an anticonvulsant mood stabilizer, a predominant history of manic relapse, and a strong therapeutic alliance as additional reasons to view LAIs as usually appropriate.
Regardless of the assumption of adherence or nonadherence, in most cases in which patients had an established bipolar diagnosis, more than half of the expert panel said use of an LAI was extremely appropriate.
In patients with an established diagnosis of bipolar disorder with questionable treatment adherence, respondents strongly endorsed the idea that it was usually appropriate to use LAIs as first-line treatment if the patients had a history of two or more hospitalizations for bipolar relapses, homelessness or an otherwise unstable living arrangement, violence toward others, and poor insight into their illness.
The panel members were blinded to the study’s sponsor, which was Otsuka. All respondents had an average of 25 years of clinical experience and an average of 22 years of research experience, and all had extensive expertise in the use of two or more LAIs, although no specific antipsychotic brand names were included in the survey.
Just more than one-third of respondents reported spending all or most of their professional time seeing patients, and one-fifth reported that they saw patients half of the time. The average age of patients seen by the respondents was 35-65 years.
Dr. Sajatovic disclosed receiving research grants from the National Institutes of Health, Alkermes, Janssen, Merck, and several other pharmaceutical companies and foundations; serving as a consultant for numerous entities, including Otsuka; and receiving royalties from UpToDate, and several publishing companies.
MIAMI – Expert clinicians endorsed long-acting injectables as a preferred treatment for bipolar I disorder on the basis of patient characteristics and treatment history, rather than on an assumed level of treatment adherence, according to a small survey.
“Just over three-quarters of the experts we surveyed said they were ‘somewhat’ or ‘not very’ confident about their ability to assess their patients’ adherence,” said Martha Sajatovic, MD, who presented the data during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The finding reflects a shift, according to Dr. Sajatovic, professor of psychiatry and neurology, and the Willard Brown Chair in Neurological Outcomes Research, at Case Western University in Cleveland.
The traditional view of using long-acting injectable antipsychotics (LAIs) for patients with bipolar I disorder is that they are appropriate only in certain cohorts, such as patients with very severe illness or at the more extreme spectrum in terms of risk, and those who are homeless or pose a risk to themselves or others, Dr. Sajatovic said. Also, when it comes to the use of LAIs, there is a lack of guidance – which might contribute to clinicians’ reluctance to prescribe or recommend them, she said.
In the survey, of the 42 experts contacted by Dr. Sajatovic and her colleagues, 34 responded. According to those respondents, 11% of their patients with bipolar disorder were being treated with LAIs, compared with one-third of all patients with schizophrenia/schizoaffective disorder.
Using a scale of 1-9, with 1 being “extremely inappropriate,” 2-3 being “usually inappropriate,” 4-6 being “sometimes appropriate,” 7-8 being “usually appropriate,” and 9 being “extremely appropriate,” all tended to favor patient characteristics and treatment history over adherence when rating criteria for treatment selection. This was true regardless of whether patients were newly diagnosed with bipolar disorder, or whether their diagnosis was established and treated with an antipsychotic for 2 or more years.
For comparison, Dr. Sajatovic and her colleagues also surveyed the expert panel members on their use of LAIs in established schizophrenia and schizoaffective disorder.
Patients with a history of two or more hospitalizations for bipolar relapses and those who were either homeless or had unstable housing were rated by most respondents as usually appropriate for LAIs as first-line treatment. For those with dubious treatment adherence, the profile was similar: LAIs were considered by a majority of respondents as usually appropriate if there was a history of two or more hospitalizations for bipolar relapses, as well as homelessness or an unstable housing situation. LAIs also were considered by a majority as usually appropriate in this cohort if there was a history of violence to others, and if patients had poor insight into their illness.
Spotty treatment adherence to medications was the most common treatment history characteristic cited for first-line prescription of LAIs in patients with an established bipolar disorder diagnosis. Other first-line LAI criteria cited by most respondents for this cohort were if they previously had done well on an LAI, and if they frequently missed clinic appointments.
Virtually all the criteria above applied to patients with established illness and questionable adherence, although the expert clinicians also largely cited a failure to respond to lithium or an anticonvulsant mood stabilizer, a predominant history of manic relapse, and a strong therapeutic alliance as additional reasons to view LAIs as usually appropriate.
Regardless of the assumption of adherence or nonadherence, in most cases in which patients had an established bipolar diagnosis, more than half of the expert panel said use of an LAI was extremely appropriate.
In patients with an established diagnosis of bipolar disorder with questionable treatment adherence, respondents strongly endorsed the idea that it was usually appropriate to use LAIs as first-line treatment if the patients had a history of two or more hospitalizations for bipolar relapses, homelessness or an otherwise unstable living arrangement, violence toward others, and poor insight into their illness.
The panel members were blinded to the study’s sponsor, which was Otsuka. All respondents had an average of 25 years of clinical experience and an average of 22 years of research experience, and all had extensive expertise in the use of two or more LAIs, although no specific antipsychotic brand names were included in the survey.
Just more than one-third of respondents reported spending all or most of their professional time seeing patients, and one-fifth reported that they saw patients half of the time. The average age of patients seen by the respondents was 35-65 years.
Dr. Sajatovic disclosed receiving research grants from the National Institutes of Health, Alkermes, Janssen, Merck, and several other pharmaceutical companies and foundations; serving as a consultant for numerous entities, including Otsuka; and receiving royalties from UpToDate, and several publishing companies.
MIAMI – Expert clinicians endorsed long-acting injectables as a preferred treatment for bipolar I disorder on the basis of patient characteristics and treatment history, rather than on an assumed level of treatment adherence, according to a small survey.
“Just over three-quarters of the experts we surveyed said they were ‘somewhat’ or ‘not very’ confident about their ability to assess their patients’ adherence,” said Martha Sajatovic, MD, who presented the data during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The finding reflects a shift, according to Dr. Sajatovic, professor of psychiatry and neurology, and the Willard Brown Chair in Neurological Outcomes Research, at Case Western University in Cleveland.
The traditional view of using long-acting injectable antipsychotics (LAIs) for patients with bipolar I disorder is that they are appropriate only in certain cohorts, such as patients with very severe illness or at the more extreme spectrum in terms of risk, and those who are homeless or pose a risk to themselves or others, Dr. Sajatovic said. Also, when it comes to the use of LAIs, there is a lack of guidance – which might contribute to clinicians’ reluctance to prescribe or recommend them, she said.
In the survey, of the 42 experts contacted by Dr. Sajatovic and her colleagues, 34 responded. According to those respondents, 11% of their patients with bipolar disorder were being treated with LAIs, compared with one-third of all patients with schizophrenia/schizoaffective disorder.
Using a scale of 1-9, with 1 being “extremely inappropriate,” 2-3 being “usually inappropriate,” 4-6 being “sometimes appropriate,” 7-8 being “usually appropriate,” and 9 being “extremely appropriate,” all tended to favor patient characteristics and treatment history over adherence when rating criteria for treatment selection. This was true regardless of whether patients were newly diagnosed with bipolar disorder, or whether their diagnosis was established and treated with an antipsychotic for 2 or more years.
For comparison, Dr. Sajatovic and her colleagues also surveyed the expert panel members on their use of LAIs in established schizophrenia and schizoaffective disorder.
Patients with a history of two or more hospitalizations for bipolar relapses and those who were either homeless or had unstable housing were rated by most respondents as usually appropriate for LAIs as first-line treatment. For those with dubious treatment adherence, the profile was similar: LAIs were considered by a majority of respondents as usually appropriate if there was a history of two or more hospitalizations for bipolar relapses, as well as homelessness or an unstable housing situation. LAIs also were considered by a majority as usually appropriate in this cohort if there was a history of violence to others, and if patients had poor insight into their illness.
Spotty treatment adherence to medications was the most common treatment history characteristic cited for first-line prescription of LAIs in patients with an established bipolar disorder diagnosis. Other first-line LAI criteria cited by most respondents for this cohort were if they previously had done well on an LAI, and if they frequently missed clinic appointments.
Virtually all the criteria above applied to patients with established illness and questionable adherence, although the expert clinicians also largely cited a failure to respond to lithium or an anticonvulsant mood stabilizer, a predominant history of manic relapse, and a strong therapeutic alliance as additional reasons to view LAIs as usually appropriate.
Regardless of the assumption of adherence or nonadherence, in most cases in which patients had an established bipolar diagnosis, more than half of the expert panel said use of an LAI was extremely appropriate.
In patients with an established diagnosis of bipolar disorder with questionable treatment adherence, respondents strongly endorsed the idea that it was usually appropriate to use LAIs as first-line treatment if the patients had a history of two or more hospitalizations for bipolar relapses, homelessness or an otherwise unstable living arrangement, violence toward others, and poor insight into their illness.
The panel members were blinded to the study’s sponsor, which was Otsuka. All respondents had an average of 25 years of clinical experience and an average of 22 years of research experience, and all had extensive expertise in the use of two or more LAIs, although no specific antipsychotic brand names were included in the survey.
Just more than one-third of respondents reported spending all or most of their professional time seeing patients, and one-fifth reported that they saw patients half of the time. The average age of patients seen by the respondents was 35-65 years.
Dr. Sajatovic disclosed receiving research grants from the National Institutes of Health, Alkermes, Janssen, Merck, and several other pharmaceutical companies and foundations; serving as a consultant for numerous entities, including Otsuka; and receiving royalties from UpToDate, and several publishing companies.
AT THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Clinicians very strongly endorsed the use long-acting injectables as first-line treatment in patients with bipolar disorder who met several criteria, including having a history of two or more hospitalizations for bipolar relapses.
Data source: A blinded, consensus survey of 34 high-prescribing clinicians experienced in treating mood and psychotic disorders.
Disclosures: Dr. Sajatovic disclosed receiving research grants from the National Institutes of Health, Alkermes, Janssen, Merck, and several other pharmaceutical companies and foundations; serving as a consultant for numerous entities, including Otsuka, which sponsored the study; and receiving royalties from UpToDate, and several publishing companies.
Reframe view of borderline personality disorder patients as survivors
WASHINGTON – A view of borderline personality disorder as neurobiological in nature can help clinicians extend their patience and empathy to these notoriously difficult-to-treat patients, according to an expert.
“Unfortunately, there are those who ... are just too frustrated by” [patients with borderline personality disorder], said Carmen V. Pinto, MD, an Elizabethtown, Ky.–based psychiatrist who specializes in treating patients with the disorder.
The diagnosis occurs in up to 2% of the population and is twice as common in women. About three-quarters of borderline personality disorder patients will attempt suicide at least once, and up to 1 in 10 complete suicide, said Dr. Pinto, assistant clinical professor of psychiatry at the University of Louisville (Ky.).
“There is an art to dealing with patients who are impulsive, and sometimes dangerous and scary,” Dr. Pinto said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education.
He emphasized the effect of unstable interpersonal relationships combined with frontolimbic brain abnormalities on the lives of patients with borderline personality disorder. In some cases, borderline personality disorder patients experienced traumatic events such as sexual abuse that was personal and ongoing – and occurred while the personality was being formed.
“These are normal people who have been exposed to abnormal stress,” Dr. Pinto said. “So you have to be careful, and see them not as victims but as survivors still suffering.”
Citing several lines of study into the neurobiochemical mechanisms of action in the disorder, Dr. Pinto discussed the role of disruption to the brain’s cortical-limbic circuit that serves as the brain’s basic stress response. In this population, an overactive amygdala and hypofunctioning frontal cortex continually signal threats even when none exist – exciting the sympathetic nervous system – as well as the endocrine and immune systems.
“The circuit gets overwhelmed, either because there really is too much to deal with, or there was poor functioning to start with, so the brain is going off like a pinball machine,” Dr. Pinto said. “If [the patients perceive] even the slightest offense, their limbic system lights up, and they have trouble turning it off, which is why it can be so difficult to deal with these folks in therapy.”
He explained the borderline personality patient’s typical negative valence as the result of this hyper-threat detection, often rooted in experiences in which people who professed to care for them acted contrary to their words, as in cases of incest. “They learn they can’t trust what is said, so they rely on nonverbal cues,” Dr. Pinto said. “They aren’t listening to what is said to them.”
Dr. Pinto cited a study of how this patient population had trouble distinguishing neutral faces from faces expressing anger or boredom, resulting in their believing that most people they encounter are unhappy with them in some way, causing them to retreat or have stressful relationships with others.
“Therapeutic neutrality is not the best way to approach this person, because they read it as ‘you are mad at me’ or ‘you’re bored with me’ or ‘you don’t like me,’ ” Dr. Pinto said, noting that he likes to reassure patients that they are doing the best they can with what they have. However, he warned against how often, in these patients’ quest to feel loved and accepted, they might ask for hugs or other contact. Rather than panic, use the opportunity to help the patient practice having healthy boundaries by explaining that not hugging them is designed to protect them, Dr. Pinto said.
Among the DSM-5 criteria for diagnosing this disorder is that the patient has an “enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture.” Because there are no imaging or laboratory tests to confirm a deviant inner experience, the clinician must turn to the patient for assessment while quelling the impulse to assign meanings to action and insight.
“You really have to be quiet and listen. They are the expert with their inner experience, and you have to let them tell you what that is,” he said, noting that the distortion of how they view themselves in relation to others is painful and pervasive, crossing all areas of their lives.
Because relationships are so difficult for these patients to develop, Dr. Pinto urged keeping in mind that it is possible they have no other therapeutic relationship in their lives. “That is a scary responsibility, to think they have no one else to talk to but you,” he said. This underscores the need for clinicians to protect themselves, too. “If I don’t feel safe, I can’t do a good job for them – and I tell them that,” Dr. Pinto said.
Global Academy and this news organization are owned by the same company. Dr. Pinto had no relevant disclosures, although he said he is a paid speaker for Otsuka, Lundbeck, Janssen, and other pharmaceutical companies.
WASHINGTON – A view of borderline personality disorder as neurobiological in nature can help clinicians extend their patience and empathy to these notoriously difficult-to-treat patients, according to an expert.
“Unfortunately, there are those who ... are just too frustrated by” [patients with borderline personality disorder], said Carmen V. Pinto, MD, an Elizabethtown, Ky.–based psychiatrist who specializes in treating patients with the disorder.
The diagnosis occurs in up to 2% of the population and is twice as common in women. About three-quarters of borderline personality disorder patients will attempt suicide at least once, and up to 1 in 10 complete suicide, said Dr. Pinto, assistant clinical professor of psychiatry at the University of Louisville (Ky.).
“There is an art to dealing with patients who are impulsive, and sometimes dangerous and scary,” Dr. Pinto said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education.
He emphasized the effect of unstable interpersonal relationships combined with frontolimbic brain abnormalities on the lives of patients with borderline personality disorder. In some cases, borderline personality disorder patients experienced traumatic events such as sexual abuse that was personal and ongoing – and occurred while the personality was being formed.
“These are normal people who have been exposed to abnormal stress,” Dr. Pinto said. “So you have to be careful, and see them not as victims but as survivors still suffering.”
Citing several lines of study into the neurobiochemical mechanisms of action in the disorder, Dr. Pinto discussed the role of disruption to the brain’s cortical-limbic circuit that serves as the brain’s basic stress response. In this population, an overactive amygdala and hypofunctioning frontal cortex continually signal threats even when none exist – exciting the sympathetic nervous system – as well as the endocrine and immune systems.
“The circuit gets overwhelmed, either because there really is too much to deal with, or there was poor functioning to start with, so the brain is going off like a pinball machine,” Dr. Pinto said. “If [the patients perceive] even the slightest offense, their limbic system lights up, and they have trouble turning it off, which is why it can be so difficult to deal with these folks in therapy.”
He explained the borderline personality patient’s typical negative valence as the result of this hyper-threat detection, often rooted in experiences in which people who professed to care for them acted contrary to their words, as in cases of incest. “They learn they can’t trust what is said, so they rely on nonverbal cues,” Dr. Pinto said. “They aren’t listening to what is said to them.”
Dr. Pinto cited a study of how this patient population had trouble distinguishing neutral faces from faces expressing anger or boredom, resulting in their believing that most people they encounter are unhappy with them in some way, causing them to retreat or have stressful relationships with others.
“Therapeutic neutrality is not the best way to approach this person, because they read it as ‘you are mad at me’ or ‘you’re bored with me’ or ‘you don’t like me,’ ” Dr. Pinto said, noting that he likes to reassure patients that they are doing the best they can with what they have. However, he warned against how often, in these patients’ quest to feel loved and accepted, they might ask for hugs or other contact. Rather than panic, use the opportunity to help the patient practice having healthy boundaries by explaining that not hugging them is designed to protect them, Dr. Pinto said.
Among the DSM-5 criteria for diagnosing this disorder is that the patient has an “enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture.” Because there are no imaging or laboratory tests to confirm a deviant inner experience, the clinician must turn to the patient for assessment while quelling the impulse to assign meanings to action and insight.
“You really have to be quiet and listen. They are the expert with their inner experience, and you have to let them tell you what that is,” he said, noting that the distortion of how they view themselves in relation to others is painful and pervasive, crossing all areas of their lives.
Because relationships are so difficult for these patients to develop, Dr. Pinto urged keeping in mind that it is possible they have no other therapeutic relationship in their lives. “That is a scary responsibility, to think they have no one else to talk to but you,” he said. This underscores the need for clinicians to protect themselves, too. “If I don’t feel safe, I can’t do a good job for them – and I tell them that,” Dr. Pinto said.
Global Academy and this news organization are owned by the same company. Dr. Pinto had no relevant disclosures, although he said he is a paid speaker for Otsuka, Lundbeck, Janssen, and other pharmaceutical companies.
WASHINGTON – A view of borderline personality disorder as neurobiological in nature can help clinicians extend their patience and empathy to these notoriously difficult-to-treat patients, according to an expert.
“Unfortunately, there are those who ... are just too frustrated by” [patients with borderline personality disorder], said Carmen V. Pinto, MD, an Elizabethtown, Ky.–based psychiatrist who specializes in treating patients with the disorder.
The diagnosis occurs in up to 2% of the population and is twice as common in women. About three-quarters of borderline personality disorder patients will attempt suicide at least once, and up to 1 in 10 complete suicide, said Dr. Pinto, assistant clinical professor of psychiatry at the University of Louisville (Ky.).
“There is an art to dealing with patients who are impulsive, and sometimes dangerous and scary,” Dr. Pinto said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education.
He emphasized the effect of unstable interpersonal relationships combined with frontolimbic brain abnormalities on the lives of patients with borderline personality disorder. In some cases, borderline personality disorder patients experienced traumatic events such as sexual abuse that was personal and ongoing – and occurred while the personality was being formed.
“These are normal people who have been exposed to abnormal stress,” Dr. Pinto said. “So you have to be careful, and see them not as victims but as survivors still suffering.”
Citing several lines of study into the neurobiochemical mechanisms of action in the disorder, Dr. Pinto discussed the role of disruption to the brain’s cortical-limbic circuit that serves as the brain’s basic stress response. In this population, an overactive amygdala and hypofunctioning frontal cortex continually signal threats even when none exist – exciting the sympathetic nervous system – as well as the endocrine and immune systems.
“The circuit gets overwhelmed, either because there really is too much to deal with, or there was poor functioning to start with, so the brain is going off like a pinball machine,” Dr. Pinto said. “If [the patients perceive] even the slightest offense, their limbic system lights up, and they have trouble turning it off, which is why it can be so difficult to deal with these folks in therapy.”
He explained the borderline personality patient’s typical negative valence as the result of this hyper-threat detection, often rooted in experiences in which people who professed to care for them acted contrary to their words, as in cases of incest. “They learn they can’t trust what is said, so they rely on nonverbal cues,” Dr. Pinto said. “They aren’t listening to what is said to them.”
Dr. Pinto cited a study of how this patient population had trouble distinguishing neutral faces from faces expressing anger or boredom, resulting in their believing that most people they encounter are unhappy with them in some way, causing them to retreat or have stressful relationships with others.
“Therapeutic neutrality is not the best way to approach this person, because they read it as ‘you are mad at me’ or ‘you’re bored with me’ or ‘you don’t like me,’ ” Dr. Pinto said, noting that he likes to reassure patients that they are doing the best they can with what they have. However, he warned against how often, in these patients’ quest to feel loved and accepted, they might ask for hugs or other contact. Rather than panic, use the opportunity to help the patient practice having healthy boundaries by explaining that not hugging them is designed to protect them, Dr. Pinto said.
Among the DSM-5 criteria for diagnosing this disorder is that the patient has an “enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture.” Because there are no imaging or laboratory tests to confirm a deviant inner experience, the clinician must turn to the patient for assessment while quelling the impulse to assign meanings to action and insight.
“You really have to be quiet and listen. They are the expert with their inner experience, and you have to let them tell you what that is,” he said, noting that the distortion of how they view themselves in relation to others is painful and pervasive, crossing all areas of their lives.
Because relationships are so difficult for these patients to develop, Dr. Pinto urged keeping in mind that it is possible they have no other therapeutic relationship in their lives. “That is a scary responsibility, to think they have no one else to talk to but you,” he said. This underscores the need for clinicians to protect themselves, too. “If I don’t feel safe, I can’t do a good job for them – and I tell them that,” Dr. Pinto said.
Global Academy and this news organization are owned by the same company. Dr. Pinto had no relevant disclosures, although he said he is a paid speaker for Otsuka, Lundbeck, Janssen, and other pharmaceutical companies.
EXPERT ANALYSIS FROM SUMMIT IN NEUROLOGY & PSYCHIATRY
First-episode psychosis is a ‘brain attack,’ and LAIs can prevent recurrence, expert says
washington – As data mount confirming the neurodegenerative effects of psychotic episodes in schizophrenia, one expert urges psychiatrists to think of psychosis as a “brain attack” which, like heart attacks, must be prevented from recurring.
“Schizophrenia doesn’t have to be progressive neurodegenerative unless patients relapse again and again, but that happens all the time because we give our patients pills they don’t take as prescribed. There are many reasons for poor adherence,” Henry A. Nasrallah, MD, said at the meeting held by Global Academy for Medical Education.
In a presentation dedicated to the emerging science reshaping views on how schizophrenia occurs, how it can be prevented, and why it is a syndrome with genetic etiologies, Dr. Nasrallah emphasized that there now exist enough data to show that timely intervention with LAIs reliably prevent relapse in most patients, thereby averting progressive neurodegeneration and subsequent disability in people who develop schizophrenia.
“Researchers now stage schizophrenia. Just like cancer, the more advanced the stage, the worse the outcome,” said Dr. Nasrallah, the Sydney W. Souers Endowed Chair and professor of psychiatry and behavioral neuroscience at Saint Louis University, told his audience. “The additional damaging effects of the second episode is what leads to clinical deterioration and can start the process of treatment resistance. But if no psychotic episodes are allowed to recur after the first episode, many patients can return to their baseline functioning, such as school or work.”
The field still is clarifying the neurodevelopmental aspects of schizophrenia, including genetic and in utero adverse events that disrupt brain development, as well as the appropriate types and timing of intervention in the prodromal phase. However, Dr. Nasrallah explained, science already has demonstrated how the neurotoxic effects of psychosis in the brain of a person with schizophrenia lead to brain tissue degradation with every psychotic episode. The result is a progressive decline in social and vocational functioning.
Psychosis is associated with activation of microglia, which are monocytic cells that cross the blood-brain barrier during fetal life, settling in the brain and ultimately comprising 10%-15% of all brain cells. Once activated, they trigger an immune response, leading to neuroinflammation and oxidative stress (free radicals). However, Dr. Nasrallah said, rather than protect the brain, these processes destroy gray and white matter – particularly in the cortical region – degrading the brain and leaving it more compromised, especially if another episode of psychosis occurs.
Another factor in the vulnerability of the brain in schizophrenia is mitochondrial dysfunction. As mitochondria are the primary source of antioxidants – such as glutathione – the deficit in antioxidants increases oxidative stress, furthering the brain’s vulnerability to tissue loss.
Among other biological processes thought to be implicated in neurodegeneration with schizophrenia, Dr. Nasrallah said, are impairment of antiapoptotic signaling, glutamate excitotoxicity, hypercortisolemia, and gamma-aminobutyric acid hypofunction.
The overall effect of these neurotoxic blows is a brain that experiences white and gray matter pathologies, leading to impaired neuroplasticity with increasing levels of white matter disconnectivity, Dr. Nasrallah said.
He pointed out that studies have shown a loss of 1% of total brain volume and 3% of gray matter volume with the first psychotic episode. Cerebral ventricles expand by about 7%. “The different parts of the brain no longer communicate properly with each other across myelinated fibers, which is postulated as an explanation for cognitive impairment, thought disorder, negative symptoms, and lack of insight – all of which can contribute to nonadherence to treatment.”
Prompt treatment of the first episode of psychosis and starting the patient on an LAI can protect the brain from another destructive round of neuroinflammation and oxidative stress. He recommends that his patients take omega-3 fatty acids to expedite the anti-inflammatory response of the antipsychotic drug. First-generation antipsychotics are not neuroprotective, according to Dr. Nasrallah, whose own research shows that haloperidol is itself neurotoxic and kills neurons – although it is an efficacious antipsychotic.
Updated American Psychiatric Association practice guidelines for treating first-episode psychosis, published in 2010, do not recommend LAIs as a first-line treatment. Neither do the National Institute of Mental Health’s Schizophrenia Patient Outcomes Research Team treatment recommendations and summary statements, published in 2009. Similarly, neither document stresses atypicals over first-generation antipsychotics.
However, Dr. Nasrallah cited a randomized, controlled study from the University of California, Los Angeles, showing that in 86 patients with first-episode psychosis who were given the same antipsychotic in either oral or LAI form, at the end of 1-year follow-up, the researchers reported a 650% higher relapse rate in the oral group (33%), compared with the LAI group (5%) (JAMA Psychiatry. 2015 Aug;72[8]:822-9).
“I tell my residents to behave like cardiologists,” Dr. Nasrallah said. “When cardiologists have a patient who experienced the first heart attack, they make it an absolute goal never to let the patient have another myocardial infarction because the first one permanently killed part of the myocardium, and a second heart attack will either kill the person or make him need a heart transplant. They implement a multifaceted intervention to achieve that goal. We psychiatrists should regard [the first episode of psychosis] as a ‘brain attack,’ and we should never let patients have another one again. The best intervention we have for this is starting an atypical LAI in first-episode patients.”
Global Academy and this news organization are owned by the same company. Dr. Nasrallah has conducted Food and Drug Administration clinical trials with LAIs and has several industry ties, including with Alkermes, Janssen, and Otsuka.
washington – As data mount confirming the neurodegenerative effects of psychotic episodes in schizophrenia, one expert urges psychiatrists to think of psychosis as a “brain attack” which, like heart attacks, must be prevented from recurring.
“Schizophrenia doesn’t have to be progressive neurodegenerative unless patients relapse again and again, but that happens all the time because we give our patients pills they don’t take as prescribed. There are many reasons for poor adherence,” Henry A. Nasrallah, MD, said at the meeting held by Global Academy for Medical Education.
In a presentation dedicated to the emerging science reshaping views on how schizophrenia occurs, how it can be prevented, and why it is a syndrome with genetic etiologies, Dr. Nasrallah emphasized that there now exist enough data to show that timely intervention with LAIs reliably prevent relapse in most patients, thereby averting progressive neurodegeneration and subsequent disability in people who develop schizophrenia.
“Researchers now stage schizophrenia. Just like cancer, the more advanced the stage, the worse the outcome,” said Dr. Nasrallah, the Sydney W. Souers Endowed Chair and professor of psychiatry and behavioral neuroscience at Saint Louis University, told his audience. “The additional damaging effects of the second episode is what leads to clinical deterioration and can start the process of treatment resistance. But if no psychotic episodes are allowed to recur after the first episode, many patients can return to their baseline functioning, such as school or work.”
The field still is clarifying the neurodevelopmental aspects of schizophrenia, including genetic and in utero adverse events that disrupt brain development, as well as the appropriate types and timing of intervention in the prodromal phase. However, Dr. Nasrallah explained, science already has demonstrated how the neurotoxic effects of psychosis in the brain of a person with schizophrenia lead to brain tissue degradation with every psychotic episode. The result is a progressive decline in social and vocational functioning.
Psychosis is associated with activation of microglia, which are monocytic cells that cross the blood-brain barrier during fetal life, settling in the brain and ultimately comprising 10%-15% of all brain cells. Once activated, they trigger an immune response, leading to neuroinflammation and oxidative stress (free radicals). However, Dr. Nasrallah said, rather than protect the brain, these processes destroy gray and white matter – particularly in the cortical region – degrading the brain and leaving it more compromised, especially if another episode of psychosis occurs.
Another factor in the vulnerability of the brain in schizophrenia is mitochondrial dysfunction. As mitochondria are the primary source of antioxidants – such as glutathione – the deficit in antioxidants increases oxidative stress, furthering the brain’s vulnerability to tissue loss.
Among other biological processes thought to be implicated in neurodegeneration with schizophrenia, Dr. Nasrallah said, are impairment of antiapoptotic signaling, glutamate excitotoxicity, hypercortisolemia, and gamma-aminobutyric acid hypofunction.
The overall effect of these neurotoxic blows is a brain that experiences white and gray matter pathologies, leading to impaired neuroplasticity with increasing levels of white matter disconnectivity, Dr. Nasrallah said.
He pointed out that studies have shown a loss of 1% of total brain volume and 3% of gray matter volume with the first psychotic episode. Cerebral ventricles expand by about 7%. “The different parts of the brain no longer communicate properly with each other across myelinated fibers, which is postulated as an explanation for cognitive impairment, thought disorder, negative symptoms, and lack of insight – all of which can contribute to nonadherence to treatment.”
Prompt treatment of the first episode of psychosis and starting the patient on an LAI can protect the brain from another destructive round of neuroinflammation and oxidative stress. He recommends that his patients take omega-3 fatty acids to expedite the anti-inflammatory response of the antipsychotic drug. First-generation antipsychotics are not neuroprotective, according to Dr. Nasrallah, whose own research shows that haloperidol is itself neurotoxic and kills neurons – although it is an efficacious antipsychotic.
Updated American Psychiatric Association practice guidelines for treating first-episode psychosis, published in 2010, do not recommend LAIs as a first-line treatment. Neither do the National Institute of Mental Health’s Schizophrenia Patient Outcomes Research Team treatment recommendations and summary statements, published in 2009. Similarly, neither document stresses atypicals over first-generation antipsychotics.
However, Dr. Nasrallah cited a randomized, controlled study from the University of California, Los Angeles, showing that in 86 patients with first-episode psychosis who were given the same antipsychotic in either oral or LAI form, at the end of 1-year follow-up, the researchers reported a 650% higher relapse rate in the oral group (33%), compared with the LAI group (5%) (JAMA Psychiatry. 2015 Aug;72[8]:822-9).
“I tell my residents to behave like cardiologists,” Dr. Nasrallah said. “When cardiologists have a patient who experienced the first heart attack, they make it an absolute goal never to let the patient have another myocardial infarction because the first one permanently killed part of the myocardium, and a second heart attack will either kill the person or make him need a heart transplant. They implement a multifaceted intervention to achieve that goal. We psychiatrists should regard [the first episode of psychosis] as a ‘brain attack,’ and we should never let patients have another one again. The best intervention we have for this is starting an atypical LAI in first-episode patients.”
Global Academy and this news organization are owned by the same company. Dr. Nasrallah has conducted Food and Drug Administration clinical trials with LAIs and has several industry ties, including with Alkermes, Janssen, and Otsuka.
washington – As data mount confirming the neurodegenerative effects of psychotic episodes in schizophrenia, one expert urges psychiatrists to think of psychosis as a “brain attack” which, like heart attacks, must be prevented from recurring.
“Schizophrenia doesn’t have to be progressive neurodegenerative unless patients relapse again and again, but that happens all the time because we give our patients pills they don’t take as prescribed. There are many reasons for poor adherence,” Henry A. Nasrallah, MD, said at the meeting held by Global Academy for Medical Education.
In a presentation dedicated to the emerging science reshaping views on how schizophrenia occurs, how it can be prevented, and why it is a syndrome with genetic etiologies, Dr. Nasrallah emphasized that there now exist enough data to show that timely intervention with LAIs reliably prevent relapse in most patients, thereby averting progressive neurodegeneration and subsequent disability in people who develop schizophrenia.
“Researchers now stage schizophrenia. Just like cancer, the more advanced the stage, the worse the outcome,” said Dr. Nasrallah, the Sydney W. Souers Endowed Chair and professor of psychiatry and behavioral neuroscience at Saint Louis University, told his audience. “The additional damaging effects of the second episode is what leads to clinical deterioration and can start the process of treatment resistance. But if no psychotic episodes are allowed to recur after the first episode, many patients can return to their baseline functioning, such as school or work.”
The field still is clarifying the neurodevelopmental aspects of schizophrenia, including genetic and in utero adverse events that disrupt brain development, as well as the appropriate types and timing of intervention in the prodromal phase. However, Dr. Nasrallah explained, science already has demonstrated how the neurotoxic effects of psychosis in the brain of a person with schizophrenia lead to brain tissue degradation with every psychotic episode. The result is a progressive decline in social and vocational functioning.
Psychosis is associated with activation of microglia, which are monocytic cells that cross the blood-brain barrier during fetal life, settling in the brain and ultimately comprising 10%-15% of all brain cells. Once activated, they trigger an immune response, leading to neuroinflammation and oxidative stress (free radicals). However, Dr. Nasrallah said, rather than protect the brain, these processes destroy gray and white matter – particularly in the cortical region – degrading the brain and leaving it more compromised, especially if another episode of psychosis occurs.
Another factor in the vulnerability of the brain in schizophrenia is mitochondrial dysfunction. As mitochondria are the primary source of antioxidants – such as glutathione – the deficit in antioxidants increases oxidative stress, furthering the brain’s vulnerability to tissue loss.
Among other biological processes thought to be implicated in neurodegeneration with schizophrenia, Dr. Nasrallah said, are impairment of antiapoptotic signaling, glutamate excitotoxicity, hypercortisolemia, and gamma-aminobutyric acid hypofunction.
The overall effect of these neurotoxic blows is a brain that experiences white and gray matter pathologies, leading to impaired neuroplasticity with increasing levels of white matter disconnectivity, Dr. Nasrallah said.
He pointed out that studies have shown a loss of 1% of total brain volume and 3% of gray matter volume with the first psychotic episode. Cerebral ventricles expand by about 7%. “The different parts of the brain no longer communicate properly with each other across myelinated fibers, which is postulated as an explanation for cognitive impairment, thought disorder, negative symptoms, and lack of insight – all of which can contribute to nonadherence to treatment.”
Prompt treatment of the first episode of psychosis and starting the patient on an LAI can protect the brain from another destructive round of neuroinflammation and oxidative stress. He recommends that his patients take omega-3 fatty acids to expedite the anti-inflammatory response of the antipsychotic drug. First-generation antipsychotics are not neuroprotective, according to Dr. Nasrallah, whose own research shows that haloperidol is itself neurotoxic and kills neurons – although it is an efficacious antipsychotic.
Updated American Psychiatric Association practice guidelines for treating first-episode psychosis, published in 2010, do not recommend LAIs as a first-line treatment. Neither do the National Institute of Mental Health’s Schizophrenia Patient Outcomes Research Team treatment recommendations and summary statements, published in 2009. Similarly, neither document stresses atypicals over first-generation antipsychotics.
However, Dr. Nasrallah cited a randomized, controlled study from the University of California, Los Angeles, showing that in 86 patients with first-episode psychosis who were given the same antipsychotic in either oral or LAI form, at the end of 1-year follow-up, the researchers reported a 650% higher relapse rate in the oral group (33%), compared with the LAI group (5%) (JAMA Psychiatry. 2015 Aug;72[8]:822-9).
“I tell my residents to behave like cardiologists,” Dr. Nasrallah said. “When cardiologists have a patient who experienced the first heart attack, they make it an absolute goal never to let the patient have another myocardial infarction because the first one permanently killed part of the myocardium, and a second heart attack will either kill the person or make him need a heart transplant. They implement a multifaceted intervention to achieve that goal. We psychiatrists should regard [the first episode of psychosis] as a ‘brain attack,’ and we should never let patients have another one again. The best intervention we have for this is starting an atypical LAI in first-episode patients.”
Global Academy and this news organization are owned by the same company. Dr. Nasrallah has conducted Food and Drug Administration clinical trials with LAIs and has several industry ties, including with Alkermes, Janssen, and Otsuka.
AT SUMMIT IN NEUROLOGY & PSYCHIATRY
Novel female sexual dysfunction drug effective, phase III studies show
MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.
Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.
The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.
Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.
“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”
Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.
Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.
Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.
“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”
Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.
Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.
“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”
In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*
The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.
MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.
Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.
The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.
Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.
“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”
Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.
Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.
Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.
“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”
Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.
Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.
“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”
In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*
The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.
MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.
Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.
The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.
Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.
“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”
Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.
Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.
Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.
“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”
Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.
Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.
“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”
In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*
The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.
AT THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Bremelanotide demonstrated statistical significance when meeting its coprimary endpoints of increased sexual desire and decreased distress over hyposexuality. The drug also was associated with significant improvements in overall sexual function.
Data source: Two phase III, multicenter studies of 1,247 premenopausal women with hypoactive sexual desire disorder (HSDD) without depression randomized to either placebo or bremelanotide 1.75 mg to use as needed for 24 weeks.
Disclosures: The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin; Valeant* and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.
Treatment response rates for psychotic bipolar depression similar to those without
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
AT THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Patients with psychotic or nonpsychotic bipolar depression responded equally well to lithium and quetiapine when compared with response rates in patients without bipolar depression.
Data source: A secondary analysis of 32 patients from a multisite, randomized, controlled trial of 482 patients with bipolar disorder I or bipolar II and psychosis, assigned to receive either lithium or quetiapine for 6 months.
Disclosures: Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
Nautical metaphors build physician resilience, beat burnout
SCOTTSDALE, ARIZ. – Linda L.M. Worley, MD, was stunned when a meeting she’d requested with her supervisor to address a shortage of beds turned into a rebuke.
“You’re on the tenure track, Linda. If you want to keep your job 6 years from now, you’d best pick up the pace. You need to see 20 private patients a week, and get moving on your research and publications,” Dr. Worley remembers the supervisor saying. At the time, she was a 32-year-old mother of two, wife, academic faculty physician, and sole attending running a general hospital consultation liaison psychiatry department and the college of medicine student mental health service. She also worked as the 24/7 on-call psychiatrist for a week at a time, said Dr. Worley, now a staff psychiatrist in the Fayetteville, Ark., Veterans Health Care System of the Ozarks and chief mental health officer for South Central VA Health Care Network.
Over the decades of an academic medical career complete with tenure, and dozens of published articles and book chapters, Dr. Worley has developed a system for achieving success while avoiding burnout, based on nautical references. In a session cofacilitated by Cynthia M. Stonnington, MD, chair of psychiatry and psychology at the Mayo Clinic’s campus in Scottsdale, Ariz., Dr. Worley presented her tips for self-care at the annual meeting of the American College of Psychiatrists.
“I use the nautical framework as a bio-psycho-social-spiritual model,” Dr. Worley said in an interview. “I teach it to medical students; I teach it to residents; I teach it to distressed physicians. I even teach it to patients when I am explaining a framework for a necessary treatment approach. With sailing, you have to stay in balance. That’s the same with taking good care of ourselves so we are less likely to get sick physically and mentally,” said Dr. Worley, who commutes to Nashville, Tenn., several times a year as part of her appointment as an adjunct professor of medicine at Vanderbilt University.
Her “Smooth Sailing Life” seminars have evolved over the past 20 years and are rooted in her training in psychosomatic medicine, which she said emphasizes the complexity of the entire person. “It’s about the biology and about the emotions, and the bridge between them,” according to Dr. Worley, who has a website, SmoothSailingLife.com, and is working on a book aimed at helping to meet what she said has been a steadily growing thirst for her approach to developing resilience.
“I am not studying anyone, but I am helping people to self-diagnose. I teach people how to avoid having to see a psychiatrist or a mental health provider but also to feel good about reaching out for help when necessary,” she said. “Life is far too short to suffer needlessly.”
In the interview, Dr. Worley said she adapts her presentations to the venue and the time allowed. Key aspects of her system include:
• Care for your yacht, which is the body, including the brain. “You only get one, and if you’re going to have a chance of winning the regatta, you have to take care of it. This means getting good sleep, nutrition, exercise, preventive care, rest, and rejuvenation, including vacation,” Dr. Worley said.
• Chart your course; have a navigational plan that includes your life goals and aspirations. Identify and rely upon “landmarks,” such as being a good spouse, mother, physician, or friend for the most authentic definition of personal success. “These are like buoys that keep us sailing in the right direction,” she said.
• Reef in your sails, meaning mind the “winds that come at us from every side,” she said. This includes triaging tasks and not letting perfectionism get in the way. “Perfectionists take too long to tack; they don’t know when it’s time to turn in the other direction,” she said. “If you want to finish the race, you have to do the best you can in the time you have.” This was the lesson Dr. Worley said she learned that day when she was a young physician feeling overwhelmed.
• Empty your bilge, the nautical term for removing waste water from within the hull. Dr. Worley uses this as a metaphor for identifying and expressing negative emotions of fear, anxiety, sadness, and frustration. “These vital emotions are giving us important messages. It is important to recognize that they are present. Name and accept them, and understand what they are trying to tell us. Is it a symptom of an underlying illness that needs treatment? A conflict in a relationship? A need not being met? Are you living your deepest values? Express the emotions and sort through the best response,” she said. “It’s all part of emotional intelligence.”
• Keep an even keel, which is Dr. Worley’s way of stating the importance of being connected to love and to living your deepest values. “The keel is your character, your connection to meaning, a spiritual connection. In medicine, we shy away from that. I have only lately ventured into talking about this,” she said, noting that this connection can come in numerous ways, such as meditation, and being in nature or with animals. “It’s very personal. It’s hard to quantify, but I have witnessed it and its healing power within the therapeutic alliance.”
In break-out sessions during her well-attended talk at the meeting, Dr. Worley listened as psychiatrists of all levels of experience and responsibility, ranging from medical directors to those in private community practice, shared the kinds of concerns she said she often encounters in her role as a core faculty member of the Program for Distressed Physicians at the Vanderbilt Center for Professional Health.
“Changes in medicine have been so frustrating; physicians are at their wits’ end. We don’t recruit people into medicine because they have a skill set for expressing their emotions, or taking care of themselves, or dealing with conflict,” she said. “That’s okay. They can learn it.”
SCOTTSDALE, ARIZ. – Linda L.M. Worley, MD, was stunned when a meeting she’d requested with her supervisor to address a shortage of beds turned into a rebuke.
“You’re on the tenure track, Linda. If you want to keep your job 6 years from now, you’d best pick up the pace. You need to see 20 private patients a week, and get moving on your research and publications,” Dr. Worley remembers the supervisor saying. At the time, she was a 32-year-old mother of two, wife, academic faculty physician, and sole attending running a general hospital consultation liaison psychiatry department and the college of medicine student mental health service. She also worked as the 24/7 on-call psychiatrist for a week at a time, said Dr. Worley, now a staff psychiatrist in the Fayetteville, Ark., Veterans Health Care System of the Ozarks and chief mental health officer for South Central VA Health Care Network.
Over the decades of an academic medical career complete with tenure, and dozens of published articles and book chapters, Dr. Worley has developed a system for achieving success while avoiding burnout, based on nautical references. In a session cofacilitated by Cynthia M. Stonnington, MD, chair of psychiatry and psychology at the Mayo Clinic’s campus in Scottsdale, Ariz., Dr. Worley presented her tips for self-care at the annual meeting of the American College of Psychiatrists.
“I use the nautical framework as a bio-psycho-social-spiritual model,” Dr. Worley said in an interview. “I teach it to medical students; I teach it to residents; I teach it to distressed physicians. I even teach it to patients when I am explaining a framework for a necessary treatment approach. With sailing, you have to stay in balance. That’s the same with taking good care of ourselves so we are less likely to get sick physically and mentally,” said Dr. Worley, who commutes to Nashville, Tenn., several times a year as part of her appointment as an adjunct professor of medicine at Vanderbilt University.
Her “Smooth Sailing Life” seminars have evolved over the past 20 years and are rooted in her training in psychosomatic medicine, which she said emphasizes the complexity of the entire person. “It’s about the biology and about the emotions, and the bridge between them,” according to Dr. Worley, who has a website, SmoothSailingLife.com, and is working on a book aimed at helping to meet what she said has been a steadily growing thirst for her approach to developing resilience.
“I am not studying anyone, but I am helping people to self-diagnose. I teach people how to avoid having to see a psychiatrist or a mental health provider but also to feel good about reaching out for help when necessary,” she said. “Life is far too short to suffer needlessly.”
In the interview, Dr. Worley said she adapts her presentations to the venue and the time allowed. Key aspects of her system include:
• Care for your yacht, which is the body, including the brain. “You only get one, and if you’re going to have a chance of winning the regatta, you have to take care of it. This means getting good sleep, nutrition, exercise, preventive care, rest, and rejuvenation, including vacation,” Dr. Worley said.
• Chart your course; have a navigational plan that includes your life goals and aspirations. Identify and rely upon “landmarks,” such as being a good spouse, mother, physician, or friend for the most authentic definition of personal success. “These are like buoys that keep us sailing in the right direction,” she said.
• Reef in your sails, meaning mind the “winds that come at us from every side,” she said. This includes triaging tasks and not letting perfectionism get in the way. “Perfectionists take too long to tack; they don’t know when it’s time to turn in the other direction,” she said. “If you want to finish the race, you have to do the best you can in the time you have.” This was the lesson Dr. Worley said she learned that day when she was a young physician feeling overwhelmed.
• Empty your bilge, the nautical term for removing waste water from within the hull. Dr. Worley uses this as a metaphor for identifying and expressing negative emotions of fear, anxiety, sadness, and frustration. “These vital emotions are giving us important messages. It is important to recognize that they are present. Name and accept them, and understand what they are trying to tell us. Is it a symptom of an underlying illness that needs treatment? A conflict in a relationship? A need not being met? Are you living your deepest values? Express the emotions and sort through the best response,” she said. “It’s all part of emotional intelligence.”
• Keep an even keel, which is Dr. Worley’s way of stating the importance of being connected to love and to living your deepest values. “The keel is your character, your connection to meaning, a spiritual connection. In medicine, we shy away from that. I have only lately ventured into talking about this,” she said, noting that this connection can come in numerous ways, such as meditation, and being in nature or with animals. “It’s very personal. It’s hard to quantify, but I have witnessed it and its healing power within the therapeutic alliance.”
In break-out sessions during her well-attended talk at the meeting, Dr. Worley listened as psychiatrists of all levels of experience and responsibility, ranging from medical directors to those in private community practice, shared the kinds of concerns she said she often encounters in her role as a core faculty member of the Program for Distressed Physicians at the Vanderbilt Center for Professional Health.
“Changes in medicine have been so frustrating; physicians are at their wits’ end. We don’t recruit people into medicine because they have a skill set for expressing their emotions, or taking care of themselves, or dealing with conflict,” she said. “That’s okay. They can learn it.”
SCOTTSDALE, ARIZ. – Linda L.M. Worley, MD, was stunned when a meeting she’d requested with her supervisor to address a shortage of beds turned into a rebuke.
“You’re on the tenure track, Linda. If you want to keep your job 6 years from now, you’d best pick up the pace. You need to see 20 private patients a week, and get moving on your research and publications,” Dr. Worley remembers the supervisor saying. At the time, she was a 32-year-old mother of two, wife, academic faculty physician, and sole attending running a general hospital consultation liaison psychiatry department and the college of medicine student mental health service. She also worked as the 24/7 on-call psychiatrist for a week at a time, said Dr. Worley, now a staff psychiatrist in the Fayetteville, Ark., Veterans Health Care System of the Ozarks and chief mental health officer for South Central VA Health Care Network.
Over the decades of an academic medical career complete with tenure, and dozens of published articles and book chapters, Dr. Worley has developed a system for achieving success while avoiding burnout, based on nautical references. In a session cofacilitated by Cynthia M. Stonnington, MD, chair of psychiatry and psychology at the Mayo Clinic’s campus in Scottsdale, Ariz., Dr. Worley presented her tips for self-care at the annual meeting of the American College of Psychiatrists.
“I use the nautical framework as a bio-psycho-social-spiritual model,” Dr. Worley said in an interview. “I teach it to medical students; I teach it to residents; I teach it to distressed physicians. I even teach it to patients when I am explaining a framework for a necessary treatment approach. With sailing, you have to stay in balance. That’s the same with taking good care of ourselves so we are less likely to get sick physically and mentally,” said Dr. Worley, who commutes to Nashville, Tenn., several times a year as part of her appointment as an adjunct professor of medicine at Vanderbilt University.
Her “Smooth Sailing Life” seminars have evolved over the past 20 years and are rooted in her training in psychosomatic medicine, which she said emphasizes the complexity of the entire person. “It’s about the biology and about the emotions, and the bridge between them,” according to Dr. Worley, who has a website, SmoothSailingLife.com, and is working on a book aimed at helping to meet what she said has been a steadily growing thirst for her approach to developing resilience.
“I am not studying anyone, but I am helping people to self-diagnose. I teach people how to avoid having to see a psychiatrist or a mental health provider but also to feel good about reaching out for help when necessary,” she said. “Life is far too short to suffer needlessly.”
In the interview, Dr. Worley said she adapts her presentations to the venue and the time allowed. Key aspects of her system include:
• Care for your yacht, which is the body, including the brain. “You only get one, and if you’re going to have a chance of winning the regatta, you have to take care of it. This means getting good sleep, nutrition, exercise, preventive care, rest, and rejuvenation, including vacation,” Dr. Worley said.
• Chart your course; have a navigational plan that includes your life goals and aspirations. Identify and rely upon “landmarks,” such as being a good spouse, mother, physician, or friend for the most authentic definition of personal success. “These are like buoys that keep us sailing in the right direction,” she said.
• Reef in your sails, meaning mind the “winds that come at us from every side,” she said. This includes triaging tasks and not letting perfectionism get in the way. “Perfectionists take too long to tack; they don’t know when it’s time to turn in the other direction,” she said. “If you want to finish the race, you have to do the best you can in the time you have.” This was the lesson Dr. Worley said she learned that day when she was a young physician feeling overwhelmed.
• Empty your bilge, the nautical term for removing waste water from within the hull. Dr. Worley uses this as a metaphor for identifying and expressing negative emotions of fear, anxiety, sadness, and frustration. “These vital emotions are giving us important messages. It is important to recognize that they are present. Name and accept them, and understand what they are trying to tell us. Is it a symptom of an underlying illness that needs treatment? A conflict in a relationship? A need not being met? Are you living your deepest values? Express the emotions and sort through the best response,” she said. “It’s all part of emotional intelligence.”
• Keep an even keel, which is Dr. Worley’s way of stating the importance of being connected to love and to living your deepest values. “The keel is your character, your connection to meaning, a spiritual connection. In medicine, we shy away from that. I have only lately ventured into talking about this,” she said, noting that this connection can come in numerous ways, such as meditation, and being in nature or with animals. “It’s very personal. It’s hard to quantify, but I have witnessed it and its healing power within the therapeutic alliance.”
In break-out sessions during her well-attended talk at the meeting, Dr. Worley listened as psychiatrists of all levels of experience and responsibility, ranging from medical directors to those in private community practice, shared the kinds of concerns she said she often encounters in her role as a core faculty member of the Program for Distressed Physicians at the Vanderbilt Center for Professional Health.
“Changes in medicine have been so frustrating; physicians are at their wits’ end. We don’t recruit people into medicine because they have a skill set for expressing their emotions, or taking care of themselves, or dealing with conflict,” she said. “That’s okay. They can learn it.”
EXPERT ANALYSIS FROM THE AMERICAN COLLEGE OF PSYCHIATRISTS MEETING
Postop satisfaction scores not tied to restricted opioid prescribing
Reduced opioid prescribing did not correlate with inpatient pain management scores, a study has shown.
The Centers for Medicare & Medicaid Services announced recently that, as of 2018, pain management will no longer be rated in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, citing concerns that patient satisfaction surveys given at the time of postoperative discharge incentivizes clinicians to over-prescribe pain medication. Surgical patients are key contributors to HCAHPS scores, and opioids account for almost 40% of surgical prescriptions, according to the study.
A new study throws some shade on the CMS decision to delete pain management from the HCAHPS survey.
Pain management scores were calculated as the percentage of patients who reported that their pain was “always” well controlled. The pain dimension was calculated from the number of opioid prescriptions and also pain management scores compared to national benchmarks. Hospitals were then grouped into quintiles according to opioid prescriptions measured in oral morphine equivalents. The first quintile has the lowest number of prescriptions.
Unadjusted comparisons showed no significant differences in pain management or pain dimension scores between the first and fifth quintiles of hospitals. For pain management scores that ranked hospital staff as always controlling pain, the first quintile had a mean score of 69.5 (95% confidence interval, 66.7-71.7) out of 100, compared with 69.1 for the fifth quintile (95% CI, 67.2-71.4). On a scale of 1-10, pain dimension scores in the first quintile averaged 1.9 (mean 95% CI, 1.5-2.0), compared with 1.4 in the fifth quintile (mean 95% CI, 0.9-1.9).
So, for these institutions, the number of pain prescriptions was not correlated with HCAHPS scores for pain management. The study suggests that the concern that reducing opioid prescriptions may have a negative impact on patient satisfaction assessments may not be realized.
Other analyses controlling for a variety of comorbidities also showed no correlations between pain management scores and opioid prescribing. Of the surgeries considered – orthopedic, general, gynecologic, cancer, cardiac, and vascular – gynecologic procedures were most likely to be associated with improved pain management and pain dimension scores.
Dr. Brummett disclosed relationships with Tonix and Neuros Medical. He also holds a patent for peripheral perineural dexmedetomidine. Mr. Syrjamaki and Dr. Dupree received support from Blue Cross Blue Shield of Michigan for their respective roles in the Michigan Value Collaborative. Dr. Waljee is an unpaid consultant for 3MHealth.
Reduced opioid prescribing did not correlate with inpatient pain management scores, a study has shown.
The Centers for Medicare & Medicaid Services announced recently that, as of 2018, pain management will no longer be rated in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, citing concerns that patient satisfaction surveys given at the time of postoperative discharge incentivizes clinicians to over-prescribe pain medication. Surgical patients are key contributors to HCAHPS scores, and opioids account for almost 40% of surgical prescriptions, according to the study.
A new study throws some shade on the CMS decision to delete pain management from the HCAHPS survey.
Pain management scores were calculated as the percentage of patients who reported that their pain was “always” well controlled. The pain dimension was calculated from the number of opioid prescriptions and also pain management scores compared to national benchmarks. Hospitals were then grouped into quintiles according to opioid prescriptions measured in oral morphine equivalents. The first quintile has the lowest number of prescriptions.
Unadjusted comparisons showed no significant differences in pain management or pain dimension scores between the first and fifth quintiles of hospitals. For pain management scores that ranked hospital staff as always controlling pain, the first quintile had a mean score of 69.5 (95% confidence interval, 66.7-71.7) out of 100, compared with 69.1 for the fifth quintile (95% CI, 67.2-71.4). On a scale of 1-10, pain dimension scores in the first quintile averaged 1.9 (mean 95% CI, 1.5-2.0), compared with 1.4 in the fifth quintile (mean 95% CI, 0.9-1.9).
So, for these institutions, the number of pain prescriptions was not correlated with HCAHPS scores for pain management. The study suggests that the concern that reducing opioid prescriptions may have a negative impact on patient satisfaction assessments may not be realized.
Other analyses controlling for a variety of comorbidities also showed no correlations between pain management scores and opioid prescribing. Of the surgeries considered – orthopedic, general, gynecologic, cancer, cardiac, and vascular – gynecologic procedures were most likely to be associated with improved pain management and pain dimension scores.
Dr. Brummett disclosed relationships with Tonix and Neuros Medical. He also holds a patent for peripheral perineural dexmedetomidine. Mr. Syrjamaki and Dr. Dupree received support from Blue Cross Blue Shield of Michigan for their respective roles in the Michigan Value Collaborative. Dr. Waljee is an unpaid consultant for 3MHealth.
Reduced opioid prescribing did not correlate with inpatient pain management scores, a study has shown.
The Centers for Medicare & Medicaid Services announced recently that, as of 2018, pain management will no longer be rated in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, citing concerns that patient satisfaction surveys given at the time of postoperative discharge incentivizes clinicians to over-prescribe pain medication. Surgical patients are key contributors to HCAHPS scores, and opioids account for almost 40% of surgical prescriptions, according to the study.
A new study throws some shade on the CMS decision to delete pain management from the HCAHPS survey.
Pain management scores were calculated as the percentage of patients who reported that their pain was “always” well controlled. The pain dimension was calculated from the number of opioid prescriptions and also pain management scores compared to national benchmarks. Hospitals were then grouped into quintiles according to opioid prescriptions measured in oral morphine equivalents. The first quintile has the lowest number of prescriptions.
Unadjusted comparisons showed no significant differences in pain management or pain dimension scores between the first and fifth quintiles of hospitals. For pain management scores that ranked hospital staff as always controlling pain, the first quintile had a mean score of 69.5 (95% confidence interval, 66.7-71.7) out of 100, compared with 69.1 for the fifth quintile (95% CI, 67.2-71.4). On a scale of 1-10, pain dimension scores in the first quintile averaged 1.9 (mean 95% CI, 1.5-2.0), compared with 1.4 in the fifth quintile (mean 95% CI, 0.9-1.9).
So, for these institutions, the number of pain prescriptions was not correlated with HCAHPS scores for pain management. The study suggests that the concern that reducing opioid prescriptions may have a negative impact on patient satisfaction assessments may not be realized.
Other analyses controlling for a variety of comorbidities also showed no correlations between pain management scores and opioid prescribing. Of the surgeries considered – orthopedic, general, gynecologic, cancer, cardiac, and vascular – gynecologic procedures were most likely to be associated with improved pain management and pain dimension scores.
Dr. Brummett disclosed relationships with Tonix and Neuros Medical. He also holds a patent for peripheral perineural dexmedetomidine. Mr. Syrjamaki and Dr. Dupree received support from Blue Cross Blue Shield of Michigan for their respective roles in the Michigan Value Collaborative. Dr. Waljee is an unpaid consultant for 3MHealth.
Key clinical point:
Major finding: No significant differences between top and bottom quintiles of 47 Michigan hospitals’ opioid prescribing patterns existed when comparing their HCAHPS scores.
Data source: Pharmacy and insurance claims and HCAHPS pain management for 31,481 surgery patients between 2012 and 2014.
Disclosures: Dr. Brummett disclosed relationships with Tonix and Neuros Medical. He also holds a patent for peripheral perineural dexmedetomidine. Mr. Syrjamaki and Dr. Dupree received support from Blue Cross Blue Shield of Michigan for their respective roles in the Michigan Value Collaborative. Dr. Waljee is an unpaid consultant for 3MHealth.
Canagliflozin gets boxed warning for amputation
The Food and Drug Administration has added a boxed warning to the label of diabetes drug canagliflozin for the risk of lower limb amputation.
The agency cited data from two clinical trials showing nearly double the risk of leg and foot amputations in patients treated with the canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, compared with placebo, in a recent statement.
The trials, which followed participants for an average of 5.7 and 2.1 years, respectively, showed that lower limb infections, gangrene, diabetic foot ulcers, and ischemia commonly occurred prior to the need for amputation.
The boxed warning advises physicians to consider a patient’s history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers before prescribing canagliflozin and to monitor patients for pain, tenderness, sores, ulcers, or infections on the feet or legs.
Consider discontinuing canagliflozin in these patients, as well as those with symptoms of hypotension, ketoacidosis, elevated serum potassium levels, severe urinary tract infections, hypoglycemia in combination with other prescription diabetes medicines, yeast infections, bone breaks, and increased cholesterol, according to the FDA.
The FDA first issued a safety communication on canagliflozin about a year ago but, at the time, did not advise assessing a patient’s risk for amputation.
Canagliflozin, marketed as Invokana, Invokamet, and Invokamet XR by Janssen Pharmaceuticals, was approved by the FDA in March 2013.
Adverse events involving canagliflozin – or any drug – should be reported to the FDA MedWatch program.
The Food and Drug Administration has added a boxed warning to the label of diabetes drug canagliflozin for the risk of lower limb amputation.
The agency cited data from two clinical trials showing nearly double the risk of leg and foot amputations in patients treated with the canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, compared with placebo, in a recent statement.
The trials, which followed participants for an average of 5.7 and 2.1 years, respectively, showed that lower limb infections, gangrene, diabetic foot ulcers, and ischemia commonly occurred prior to the need for amputation.
The boxed warning advises physicians to consider a patient’s history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers before prescribing canagliflozin and to monitor patients for pain, tenderness, sores, ulcers, or infections on the feet or legs.
Consider discontinuing canagliflozin in these patients, as well as those with symptoms of hypotension, ketoacidosis, elevated serum potassium levels, severe urinary tract infections, hypoglycemia in combination with other prescription diabetes medicines, yeast infections, bone breaks, and increased cholesterol, according to the FDA.
The FDA first issued a safety communication on canagliflozin about a year ago but, at the time, did not advise assessing a patient’s risk for amputation.
Canagliflozin, marketed as Invokana, Invokamet, and Invokamet XR by Janssen Pharmaceuticals, was approved by the FDA in March 2013.
Adverse events involving canagliflozin – or any drug – should be reported to the FDA MedWatch program.
The Food and Drug Administration has added a boxed warning to the label of diabetes drug canagliflozin for the risk of lower limb amputation.
The agency cited data from two clinical trials showing nearly double the risk of leg and foot amputations in patients treated with the canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, compared with placebo, in a recent statement.
The trials, which followed participants for an average of 5.7 and 2.1 years, respectively, showed that lower limb infections, gangrene, diabetic foot ulcers, and ischemia commonly occurred prior to the need for amputation.
The boxed warning advises physicians to consider a patient’s history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers before prescribing canagliflozin and to monitor patients for pain, tenderness, sores, ulcers, or infections on the feet or legs.
Consider discontinuing canagliflozin in these patients, as well as those with symptoms of hypotension, ketoacidosis, elevated serum potassium levels, severe urinary tract infections, hypoglycemia in combination with other prescription diabetes medicines, yeast infections, bone breaks, and increased cholesterol, according to the FDA.
The FDA first issued a safety communication on canagliflozin about a year ago but, at the time, did not advise assessing a patient’s risk for amputation.
Canagliflozin, marketed as Invokana, Invokamet, and Invokamet XR by Janssen Pharmaceuticals, was approved by the FDA in March 2013.
Adverse events involving canagliflozin – or any drug – should be reported to the FDA MedWatch program.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The Food and Drug Administration has added a boxed warning to the label of diabetes drug canagliflozin for the risk of lower limb amputation.</metaDescription> <articlePDF/> <teaserImage>171309</teaserImage> <teaser>The risk of lower limb amputation associated with canagliflozin is now great enough to receive a boxed warning.</teaser> <title>Canagliflozin gets boxed warning for amputation</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels> <wireChannel>diabetes_endo_met</wireChannel> <wireChannel>top stories</wireChannel> 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</publicationData> </publications_g> <publications> <term>33</term> <term canonical="true">34</term> <term>15</term> <term>21</term> <term>13</term> <term>5</term> </publications> <sections> <term canonical="true">27979</term> </sections> <topics> <term canonical="true">205</term> <term>313</term> <term>39212</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24006240.jpg</altRep> <description role="drol:caption"/> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Canagliflozin gets boxed warning for amputation</title> <deck/> </itemMeta> <itemContent> <p>The Food and Drug Administration has added a boxed warning to the label of diabetes drug canagliflozin for the risk of lower limb amputation.</p> <p>The agency cited data from two clinical trials showing nearly double the risk of leg and foot amputations in patients treated with the canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, compared with placebo, in a recent <span class="Hyperlink"><a href="https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm558605.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery">statement</a></span>. <br/><br/>[[{"fid":"171309","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":""},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]Although amputations – sometimes multiple – involving the leg either below or above the knee, occurred, the most common amputations were of the toe and the middle of the foot, according to the <span class="Hyperlink"><a href="https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm">results</a></span> of the <span class="Hyperlink"><a href="https://clinicaltrials.gov/ct2/show/NCT01032629?term=CANVAS&rank=1">CANVAS</a></span> (Canagliflozin Cardiovascular Assessment Study) and <span class="Hyperlink"><a href="https://clinicaltrials.gov/ct2/show/NCT01989754?term=CANVAS&rank=7">CANVAS-R</a></span> (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus) trials involving more than 10,000 patients given either placebo or 100 mg or 300 mg canagliflozin. <br/><br/>The trials, which followed participants for an average of 5.7 and 2.1 years, respectively, showed that lower limb infections, gangrene, diabetic foot ulcers, and ischemia commonly occurred prior to the need for amputation. <br/><br/>The boxed warning advises physicians to consider a patient’s history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers before prescribing canagliflozin and to monitor patients for pain, tenderness, sores, ulcers, or infections on the feet or legs. <br/><br/>Consider discontinuing canagliflozin in these patients, as well as those with symptoms of hypotension, ketoacidosis, elevated serum potassium levels, severe urinary tract infections, hypoglycemia in combination with other prescription diabetes medicines, yeast infections, bone breaks, and increased cholesterol, according to the FDA.<br/><br/>The FDA first issued a safety <span class="Hyperlink"><a href="https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm501565.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery">communication</a></span> on canagliflozin about a year ago but, at the time, did not advise assessing a patient’s risk for amputation.<br/><br/>Canagliflozin, marketed as Invokana, Invokamet, and Invokamet XR by Janssen Pharmaceuticals, was <span class="Hyperlink"><a href="http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345848.htm">approved by the FDA</a></span> in March 2013. <br/><br/>Adverse events involving canagliflozin – or any drug – should be reported to the FDA <span class="Hyperlink"><a href="http://www.fda.gov/Safety/MedWatch/default.htm">MedWatch</a></span> program.</p> <p class="email"><span class="Hyperlink"><a href="mailto:wmcknight%40frontlinemedcom.com?subject=">wmcknight@frontlinemedcom.com</a></span><br/><br/>On Twitter <span class="Hyperlink"><a href="http://twitter.com/whitneymcknight">@whitneymcknight</a></span> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
