A New Treatment Approach for Bipolar Depression

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A New Treatment Approach for Bipolar Depression

Could adjunctive modafinil help?

Bipolar depression has been notoriously difficult to treat. Recent prominent studies showed no advantage for antidepressant medications added to mood stabilizers (Journal Watch Psychiatry Mar 28 2007). This 6-week, double-blind, placebo-controlled, randomized study of add-on modafinil involved 85 patients with bipolar depression and inadequate response to mood stabilizers; 49 were taking adjunctive antidepressants. Modafinil was started at 100 mg/day and increased to 200 mg/day after 1 week. The study received funding from the Stanley Foundation and the drug manufacturer.

Of the study applicants, 25% were excluded for taking monoamine oxidase inhibitors or nefazodone or having histories of manic switches with antidepressants, substance abuse, active suicidality, psychosis, unstable medical conditions, abnormal lab findings or electrocardiograms, or baseline sleep of less than 6 hours a night. At study entry, the modafinil and placebo groups had similar percentages of rapid cyclers (27% and 35%) and intake of a similar average number of other medications (3 and 4).

Starting at week 2, an intent-to-treat analysis showed significant antidepressant benefits with modafinil. Improvement in depressive symptoms of 50% or better was seen in 44% of modafinil recipients versus 23% of placebo recipients. Modafinil was not associated with reduced sleepiness or fatigue. Similar percentages of patients in the modafinil and placebo groups switched to mania (15% and 11%).

Comment: These researchers are conducting a 4-month open-treatment continuation trial. Findings from this brief, promising study suggest the appropriateness of conducting more and longer trials of adjunctive modafinil for bipolar depression, perhaps using higher doses and with better statistical control of the concomitant medications. In industry-supported studies, lamotrigine, olanzapine-fluoxetine combination, and quetiapine have seemed useful for bipolar depression, but these agents may have prominent adverse events that clinicians need to follow and treat vigilantly.

— Joel Yager, MD

Published in Journal Watch Psychiatry September 24, 2007