A Retrospective Chart Review of the Effects of Modafinil on Depression as Monotherapy and as Adjunctive Therapy

Tomas Thorne

Last Updated: February 2, 2023



Major depression is often refractory to antidepressants, and it is important to explore alternative medication treatments. Among the symptoms common with depression are energy loss/fatigue and anxiety. Modafinil has a novel mechanism of action and may have antidepressant properties. In a single outpatient clinic, data were systematically collected on all patients including those who began modafinil treatment for major depression. 

This clinician (C.P.) had used modafinil to treat major depression in patients who failed one or more adequate antidepressant treatments. To monitor changes during treatment, charting had included four rating scales: the Beck Depression Inventory, the Zung Self-Rating Depression Scale, and the Hamilton Depression and Hamilton Anxiety Rating Scales. A follow-up chart review identified 45 patients whose major depression was treated with modafinil over a 9-month period. 

The mean dose of modafinil was 184.3+/-100.0 mg/day (range=50-450 mg/day). For these 45 patients, all four rating scales showed significant improvement following 2 weeks and following 3 months of modafinil treatment. Fifteen of these patients were on modafinil monotherapy, and the remaining 30 on modafinil as an augmenting agent. For both subgroups, all three depression rating scales showed a significant improvement following 2 weeks and 3 months of modafinil treatment. This chart review provides preliminary evidence that modafinil treatment may be beneficial to those with major depression, even when unresponsive to other treatments.


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