In a study only partially funded by the manufacturer of Provigil (modafinil), 85 patients with bipolar depression, already taking mood stabilizers, were randomly assigned to augmentation with Provigil (N=41) or placebo (N=44). The average Provigil dose was 177 mg/day. Beginning at the two week point, Provigil improved depression symptoms more than placebo, and this advantage continued through the 6 week duration of the study. The Provigil patients had a 44% response rate vs. the placebo patients, who had a 23% response rate. There were no differences between the two groups in rates of manic switching.

TCPR’s Take: At the relatively modest dosing used in this study, the side effects were minimal, and there was little risk for manic switching. The effect appeared to be a true antidepressant effect and not simply a wakefulness effect, as measures of fatigue were not different in the two treatment conditions (Frye MA et al., Am J Psychiatry 2007; 164:1242-1249).