A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression.

Objective: Modafinil is approved by the U.S. Food and Drug Administration for improving wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift-work sleep disorder. This study was conducted to evaluate the efficacy and safety of adjunctive modafinil in bipolar depression, which is often characterized by excessive sleepiness and fatigue.

Method: Eighty-five patients with bipolar depression that was inadequately responsive to a mood stabilizer with or without concomitant antidepressant therapy were randomly assigned to receive adjunctive modafinil (N=41) or placebo (N=44) for 6 weeks. The primary outcome measure was baseline-to-endpoint change in score on the Inventory of Depressive Symptoms--Clinician Rated (IDS).

Results: The baseline-to-endpoint change in IDS score was significantly greater in the modafinil group (mean dose, 177 mg/day) compared with the placebo group. Improvement in depressive symptoms was significantly greater in the modafinil group by week 2, and this greater improvement was maintained at weeks 4, 5, and 6. Both the response and remission rates were significantly higher in the modafinil group (44% and 39%) compared with the placebo group (23% and 18%). During the 6-week study period, there was no difference between groups in treatment-emergent hypomania or mania (six patients in the modafinil group and five in the placebo group) or hospitalization for mania (one in each group).

Conclusions: These data suggest that adjunctive modafinil at doses of 100-200 mg a day may improve depressive symptoms in patients with bipolar disorder.