Adjunctive Antidepressants Work in Bipolar Depression, but Not Very Well

By Lorraine L. Janeczko

NEW YORK — In bipolar depression, adjunctive second-generation antidepressants work, but not very well, and their efficacy and safety remain controversial, according to results of a new systematic review and meta-analysis.

"Modern antidepressant adjunctive therapy is effective in treating acute bipolar depression. The risk of manic switch is very low during short-term treatment; however, antidepressant adjunctive therapy is not appropriate on a longer-term basis as it may increase the risk of a switch to mania," senior author Dr. Lakshmi N. Yatham, professor of psychiatry at the University of British Columbia, told Reuters Health.

'We think that the findings are consistent with the experience of many clinicians. The only surprise is that the magnitude of benefit seen was small, and that the response and remission rates did not differ between antidepressants and placebo," he said in an email. "They suggest to clinicians that it is OK to use modern antidepressant adjunctive therapy on a shorter-term basis to treat acute bipolar depression."

As the authors reported online October 26 in The Lancet Psychiatry, they searched major medical databases for randomized, double-blind, placebo-controlled trials of second-generation antidepressants used as adjuncts to a mood stabilizer or an antipsychotic in patients with acute bipolar depression.

Overall, in the six selected trials involving 1,383 patients, second-generation antidepressants were associated with a small but significant improvement in clinician-rated depressive symptom score (standardized mean difference 0.165; 95% confidence interval, 0.051 to 0.278; p=0.004).

But clinical response and remission rates did not differ significantly between patients who received adjunctive antidepressants and those who were given placebo.

Acute treatment was not associated with higher risk of treatment-emergent mania or hypomania, but 52-week extensions were associated with higher risk of affective switch (standardized mean difference 1.774; 95% CI 1.018 to 3.091; p=0.043), even with adequate mood stabilization.

These results support the recommendations of the joint guidelines of the International Society for Bipolar Disorders (ISBD) and the Canadian Network for Mood and Anxiety Treatments (CANMAT), the authors wrote.

Dr. Eduard Vieta, professor of psychiatry at the University of Barcelona and head of the Bipolar Disorders Program of the Spanish Network on Research in Mental Health (CIBERSAM), said in an email, "These results match my clinical experience, but somebody had to prove it."

"Some treatment guidelines have excluded adjunctive antidepressants as first- or even second-line options for the treatment of bipolar depression. The guidelines should be revised," said Dr. Vieta, who with Dr. Marina Garriga, also of CIBERSHAM, co-authored an editorial about the study.

Agreeing with Dr. Yatham, Dr. Vieta said, "Antidepressants should be prescribed with caution because they can cause a switch to mania."

Dr. Yatham called for larger studies exploring which types of patients are more likely to respond to antidepressant adjunctive therapy and the optimal therapy duration.

SOURCE: https://bit.ly/2eL8fQJ and https://bit.ly/2glkcx3

Lancet Psychiatry 2016.

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