First-Ever Guideline for Mixed Depression Released

Megan Brooks

May 16, 2017

One third or more of adults diagnosed with major depression have depression with mixed features and probably would do better taking an antipsychotic than an antidepressant, concludes an international panel of experts.

For patients with a major depressive episode (MDE) with mixed features (depression with some mania), antidepressants typically "don't work or might make the patient worse and could even induce mania itself or suicidality," Stephen M. Stahl, MD, PhD, Department of Psychiatry, University of California, San Diego, and chairman, Neuroscience Education Institute in Carlsbad, California, told Medscape Medical News.

For these patients, an atypical antipsychotic should be considered, he and his colleagues advise in the first guideline ever issued on recognizing and managing mixed depression.

The guideline appears in the April issue of CNS Spectrums, a theme issue devoted to mixed features in mental disorders.

Paradigm Shift

The "classical point of view" – that patients with MDEs should be treated initially with antidepressants, regardless of whether other symptoms are present – is now giving way to new a notion, writes Dr Stahl, who is editor of the journal.

"The idea is that MDEs mixed with a few symptoms of mania/hypomania should be viewed very differently in terms of their natural history, clinical outcome, and treatment, and perhaps certain antipsychotics should be given as first-line treatment rather than antidepressant monotherapy," he adds.

"This is a paradigm shift, and that happens in clinical practice. Sometimes what we once thought turns out to be partly wrong," Dr Stahl told Medscape Medical News.

"It used to be thought that a whiff of depression meant that you treat it with an antidepressant. That's how most people practice, and also since 70% of antidepressants are not prescribed by psychiatrists, that's certainly how that is done in general practice," he said.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) introduced a "mixed features" specifier for major depressive disorder. To meet DSM-5 criteria for depression with mixed features, patients must meet threshold criteria for an MDE and subthreshold symptoms of mania or hypomania, or they must have syndromal mania and subthreshold depressive symptoms.

Data regarding treatment of patients with mixed depression are very limited. There are no established treatments, "and yet it represents a third of adults with depression. In children, mixed features is probably more the rule than the exception, probably more than half," Dr Stahl noted.

To help clinicians who treat adults with MDE and mixed features, an international panel of experts on mood disorders convened to develop a consensus guideline on how best to recognize and treat mixed depression, "based on the few studies that have focused specifically on depressive mixed states as well as decades of cumulated clinical experience," the authors note.

Antidepressants a Potential Hazard

The guideline recommends that all patients who receive antidepressants for an MDE be monitored for signs of abnormal behavioral activation or psychomotor acceleration.

It also notes that use of antidepressants in patients with MDE who have mixed features "may not alleviate depressive symptoms and may pose a potential hazard for exacerbating subthreshold mania symptoms that accompany depression."

For patients presenting with a depressive episode with mixed features, in addition to antidepressant medication, alternative psychotropic agents with demonstrated efficacy in the treatment of depressive symptoms as part of MDE may be considered, the guideline says.

"While there are problems with using antipsychotics, nothing is worse than something that doesn't work or makes you worse," said Dr Stahl.

The guideline also encourages clinicians to think about the possibility of mixed features in all patients with depression.

"You will not know if a depressed patient has (hypo) manic symptoms or a positive family history of bipolar disorder unless you ask. Ask every patient. Every time," the panel advises.

"If you only look for depression, simultaneous symptoms of mania will be missed. And even with low levels of mania symptoms, you shouldn't give an antidepressant, at least not first-line," said Dr Stahl.

This guideline represents "expert consensus" on recognizing and treating mixed depression and is also a "call to action – that is, let's do the best we can with the data that are available," he added.

Other articles in the CNS Spectrums theme issue on mixed features include "Treatment of Mixed Features in Bipolar Disorder"; "Treating Mixed Mania/Hypomania"; and "Pharmacological Treatment of Mixed States."

This research had no commercial funding. The original article contains a complete list of authors' relevant financial relationships.

CNS Spectr. 2017;22:203-219. Abstract

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