Modafinil augmentation of antidepressant treatment in depression

Background: Despite a relative lack of controlled data, stimulants are ofte n used to augment antidepressant treatment in patients who have had only a partial response to first-line therapy. Modafinil is a novel psychostimulan t that has shown efficacy in, and was recently marketed for, treating exces sive daytime sleepiness associated with narcolepsy. The mechanism of action of modafinil is unknown, but, unlike other stimulants, the drug is highly selective for the central nervous system, has little effect on dopaminergic activity in the striatum, and appears to have a lower abuse potential. Method: In this retrospective case series, we describe 7 patients with DSM- IV depression (4 with major depression and 3 with bipolar depression) for w hom we used modafinil to augment a partial or nonresponse to an antidepress ant. The Hamilton Rating Scale for Depression was administered as part of r outine clinical practice prior to treatment and at each subsequent visit. Results: At doses of 100 to 200 mg/day, all 7 patients achieved full or par tial remission, generally within 1 to 2 weeks. All patients had some residu al tiredness or fatigue prior to starting modafinil, and this symptom was p articularly responsive to augmentation. Side effects were minimal and did n ot lead to discontinuation of the drug in any of the patients. Conclusion: Modafinil appears to be a drug with promise as an augmenter of antidepressants, especially in patients with residual tiredness or fatigue. It is a particularly attractive alternative to other stimulants because of its low abuse potential and Schedule IV status.