Modafinil is used off-label as an adjunctive treatment (i.e., in combination therapy) for acute depressive phase in bipolar disorder. The depressive phase of bipolar disorder may feature excessive sleepiness and fatigue. Adjunctive treatment with modafinil can be used as an augmentation for the main treatment to increase its effect and is safe and effective, especially for people who do not respond well to standard antidepressants. Modafinil does not significantly increase the risk of mood switch to mania or suicide attempts in people with bipolar disorder. Modafinil may also have cognitive benefits in people with bipolar disorder who are in a remission state.
Whereas modafinil and armodafinil are approved for narcolepsy, they have been repurposed as adjunctive treatments to alleviate symptoms of acute depressive phase in people with bipolar disorder. Drug repurposing in psychiatry is a strategy for discovering new uses for drugs that have already been approved or tested in clinical trials for other illnesses. As such, drug repurposing is a rapid, cost-effective, and reduced-risk strategy for the development of new treatment options for psychiatric disorders. 2021 meta-analysis concluded that add-on modafinil and armodafinil were more effective than placebo on response to treatment, clinical remission, and reduction in depressive symptoms, with only minor side effects, but the effect sizes are small and the quality of evidence is therefore low, limiting the clinical relevance of the evidence. Very low rates of mood swing (a change in mood from one extreme to another) have been observed with modafinil and armodafinil in depressive phase of bipolar disorder.