Reduction of daytime sleepiness in a depressive patient during adjunct treatment with modafinil

Abstract

Many patients in treatment for depression suffer prolonged daytime sleepiness despite considerable amelioration of other depressive symptoms (Kerkhofs et al., 1991; Hemmeter et al., 1998). This problem can jeopardise quick rehabilitation into everyday working life. The treatment of sleepiness in the context of ongoing therapy in depressive disorder has high relevance in psychiatric practice. In this report we present the case of an inpatient with this problem of daytime fatigue which slowed her rehabilitation. We administered modafinil, a novel agent with wake-promoting effects which is not related chemically or pharmacologically to amphetamines or methylphenidate. Unlike these latter substances it has little or no direct effect on dopaminergic activity. It requires an intact central alpha-1-adrenergic system. Modafinil has been shown to significantly reduce sleepiness and to improve levels of illness in narcolepsy patients with a favourable safety profile and low abuse potential (US modafinil in narcolepsy multicenter study group, 1998). A retrospective report of seven cases documented significant improvement in subjective wakefulness in depressed patients when modafinil was employed as an adjunct to antidepressive treatment (Menza et al., 2000). The purpose of this pilot investigation was to study polysomnographic parameters of daytime sleepiness and self-rated symptoms in a prospective manner. In addition, night sleep was measured and depressive symptoms were rated. Our depressed patient manifested residual sleepiness and underwent treatment with modafinil as an adjunct to her existing antidepressant agents. The 51-year-old secretary was admitted to the depression ward of the university psychiatric hospital by her psychiatrist after 3 years of increasing depressive symptoms following her partner’s sudden death. She suffered from depressed mood, inhibition of drive, disturbance of sleep, suicidal ideation and episodic abdominal pain. She had shut herself in her flat and neglected herself, her friends and her finances, after already having been written off work some months earlier by her psychiatrist. Fluoxetine had been prescribed, which she had taken only irregularly. On the ward she was treated with trimipramine (100 mg/day), followed by a combination with venlafaxine (525 mg/day), whilst under the anxiolytic alprazolam (1.5 mg/day). With these medications and in the inpatient setting she showed a marked recovery of mood and drive and soon wished to resume a new responsibility as secretary in a small one-man firm. She began to work in the mornings, but found that her sleepiness and lack of energy hindered her efficiency, she would return to the ward disappointed and slept with interruptions during the night. Sleep apnea and restless legs syndromes were excluded in this patient after a night’s sleep under observation in the sleep laboratory. Routine blood laboratory results, including thyroid status, were not remarkable. After a week of stable medication, substances and doses as given above, baseline measurements were made polysomnographically and using self-rating scales of sleepiness (Epworth sleepiness scale, ESS, Johns, 1991), self-rating visual analogue scales (VAS) of mood, sleepiness and relaxation and the Hamilton depression rating score (HDRS, Hamilton, 1967) in an interview with