Effects of modafinil on cognitive functions in first episode psychosis

Rationale Cognitive impairments are important determinants of functional outcome in psychosis, which are inadequately treated by antipsychotic medication. Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia. Objectives We aimed to establish modafinil's role in the adjunctive treatment of cognitive impairments in the first episode of psychosis, a time when symptoms may be more malleable than at chronic stages of the disease. Methods Forty patients with a first episode of psychosis participated in a randomised, double-blind, placebo-controlled crossover design study assessing the effects of a single dose of 200 mg modafinil on measures of executive functioning, memory, learning, impulsivity and attention. Results Modafinil improved verbal working memory (d = 0.24, p = 0.04), spatial working memory errors (d = 0.30, p = 0.0004) and strategy use (d = 0.23, p = 0.03). It also reduced discrimination errors in a task testing impulsivity. Modafinil showed no effect on impulsivity measures, sustained attention, attentional set-shifting, learning or fluency. Conclusions Modafinil selectively enhances working memory in first episode psychosis patients, which could have downstream effects on patients' social and occupational functioning.