Be on Lookout for Patients With Bipolar ‘Mixed Features,’ Advises Expert

Clinicians should be alert to the presence of mixed features in bipolar disorder—characterized by having both depressive and manic-like symptoms during the same episode—since these patients appear to have a higher risk of switching to mania when treated with antidepressants.

Patients with mixed features also tend to be younger at first onset and have higher risk of psychotic episodes, frequent hospitalizations, and suicide, explained Harvinder Singh, M.D., at a conference held by the Psychiatry Education Forum. Such patients may also take longer to reach remission, he added. Singh is the founder of the Psychiatry Education Forum.

The condition may be underdiagnosed. A retrospective study of the charts of some 331 patients with bipolar disorder over 10 years found that patients were three times more likely to meet criteria for the mixed features specifier when using the DSM-5 criteria than when using the DSM-IV-TR criteria.

Based on DSM-5 criteria, bipolar patients who are experiencing a current hypomanic, manic, or depressive episode and also present with at least three listed “core” symptoms that are typically associated with the opposite mood meet the diagnostic criteria for mixed features. For example, a clinically depressed bipolar patient who also has pressured speech, decreased need for sleep, and more involvement in risky activities would be diagnosed with the mixed features specifier. In previous editions, only patients who concurrently met criteria for a manic as well as a major depressive episode every day for at least four days received the “mixed states” diagnosis.

“In reality, we know that it’s never just these extremes in most of our patients,” Singh said. “It’s never pure mania or pure depression.”

He added that it is especially important to look for possible mixed features in young patients who are diagnosed as depressed and begin taking antidepressants but who may actually have bipolar disorder.

Singh also noted that DSM-5 excluded from the diagnostic criteria for mixed features three common symptoms: irritability, psychomotor agitation, and distractibility, because these symptoms have extensive overlap with other disorders. However, studies have found their presence in mixed episodes is associated with poor treatment outcomes. “Always be on the lookout for these symptoms, even though they are not part of the diagnostic criteria,” he said.

While Singh said the clinical interview is key to proper diagnosis of mixed features, he also recommended the use of one of three scales to aid in the identification: Hypomania checklist (HCL-32), Clinically Useful Depression Outcome Scale with DSM-5 Mixed (CUDOS-M), or the Mini-International Neuropsychiatric Interview (M.I.N.I.).

Singh reviewed research findings published since the World Federation of Societies of Biological Psychiatry (WFSBP) issued its treatment guidelines for the disorder in late 2017. Those guidelines advised that combination therapy with quetiapine plus a mood stabilizer has the strongest evidence for maintenance treatment or prevention of mixed episodes in bipolar disorder. This was followed by lithium and quetiapine monotherapy.

For treatment of patients with acute manic mixed episodes, olanzapine monotherapy rated highest, along with olanzapine plus valproate. Olanzapine was also recommended for maintenance treatment or prevention of new mixed episodes. However, there is less evidence about the use of olanzapine for treatment of acute depressive mixed episodes.

For treatment of acute depressive mixed episodes, ziprasidone augmentation was the leading recommendation. Based on research conducted since the guidelines were issued, Singh believes that cariprazine and lurasidone should also be strongly considered.

Singh strongly cautioned against the use of antidepressants in patients with mixed features bipolar disorder, noting that WFSBP guidelines rated antidepressants a grade of “F” for “lack of evidence” for use in any phase of bipolar disorder with mixed features. “We know that with antidepressant use, there is increased risk of manic switch,” he said. Furthermore, antidepressants may exacerbate the disorder and/or potentially induce mixed episodes, he said.

“Definitely there is no role for antidepressants in patients with bipolar disorder, mixed features specifier,” Singh summed up. ■