Thomas Thorne
ABSTRACT
Despite the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depression, a significant number of patients show partial or no remission of symptoms. Some evidence suggests that increased psychostimulants may be useful in the treatment of patients with residual symptoms of depression. The effectiveness of modafinil in augmenting SSRIs in depressed patients with residual fatigue or excessive daytime sleepiness has not yet been systematically investigated. In a series of 25 patients with major depressive disorder, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, who showed significant residual symptoms after an adequate trial of SSRIs (12 weeks) and who were evaluated according to the Test of Fatigue. Severity Scale (FSS), subjects scoring (3)4 received open-label modafinil escalation for a minimum of an additional 6 weeks.
Treatment response was prospectively assessed with the FSS, Epworth Sleepiness Scale (ESS), and Hamilton Rating Scale for Depression (HAM-D) during the first visit and in the second and sixth weeks. Twenty-one of 25 patients in this series who were treated with modafinil and SSRIs completed the 6-week escalation trial.At the endpoint evaluation, all patients showed significant improvement in fatigue and sleepiness in FSS and ESS scores as well as HAM-D scores (p < 0.01). In the second week, 29.4% of patients had a HAM-D score <7, which was defined as remission; this rate was 64.7% in the sixth week.
The rate of patients whose HAM-D score was reduced by more than 50%, defined as responding to treatment, was 41.1% and 76.4% in the second and sixth weeks, respectively. The results of this preliminary open-label trial suggest that modafinil may be effective in augmenting ongoing SSRI treatment for a portion of patients with major depression who have residual fatigue and somnolence. Larger, placebo-controlled trials appear warranted to investigate the clinical efficacy and tolerability of modafinil augmentation of SSRI therapy in these patients.