In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).
Dr. Charles B. Nemeroff
“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”
The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.
And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.
A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.
“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.
Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.
“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”
The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.
Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.
“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”
“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”
Other important clues of bipolarity in depressed patients include:
- Family history: Most cases are genetically driven.
- Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
- Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
- Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.
Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.
“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”
“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
Treatment resistance
When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.
“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.
There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.
Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.
“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.
“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”
Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.