Modafinil reduces microsleep during partial sleep deprivation and improves antidepressant treatment response

Objective: Sleep deprivation (SD) can induce a prompt decrease in depressive symptoms within 24 hours. Recovery sleep, naps and even very short episodes of sleep [termed, microsleep (MS)] during SD have been shown to provoke a rapid relapse into depression. This study tested the hypothesis that modafinil reduces MS during SD and augments antidepressant treatment response. Methods: 28 patients with a major depressive episode age 45.1±12.1 years (mean±SD) were investigated in a double blind placebo controlled study design. All patients were treated with mirtazapine. A partial SD (PSD) was performed after one week. Treatment with modafinil vs. placebo started during PSD and was maintained over two weeks. Sleep EEG and MS episodes were recorded with a portable EEG. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS) during and after PSD and at follow-ups after one and two weeks. Results: Modafinil treated patients showed significantly reduced MS during PSD (11.63±15.99min) compared to the placebo group (47.77±65.31min). After two weeks of treatment, the modafinil group showed a significant reduction in REM density, accompanied by a 6.4-fold higher chance to improve HDRS-scores with significant differences between groups (p<0.05). Conclusions: Modafinil reduces MS during PSD. Furthermore, modafinil augments the antidepressant treatment response to mirtazapine, presumably by modulating monoaminergic neurotransmission.

This study was supported by Swiss National Science Foundation and Cephalon GmbH