Patients with schizophrenia experience cognitive impairments associated with 
hypofunctioning of the frontal cortex. Modafinil, a novel wake-promoting agent, 
works through the sleep-wake centers of the brain to activate the cortex. This 
4-week, open-label, pilot study evaluated adjunct modafinil in patients with 
schizophrenia or schizoaffective disorder. Eleven patients received once-daily 
oral doses of modafinil (100 mg/day, days 1-14; 100 or 200 mg/day, days 15-28) 
in addition to antipsychotic therapy. Modafinil significantly improved patients' 
global functioning as assessed by a blinded clinician (week 2, P = 0.026; week 
4, P = 0.012) and the investigator (week 3, P = 0.035). Modafinil significantly 
improved overall clinical condition, with 64% and 82% of patients rated as 
clinically improved at week 4 by a blinded clinician and the investigator 
respectively. Eighty-nine percent of patients considered themselves to be 
clinically improved. Modafinil significantly improved fatigue (P = 0.025, week 
3) and tended to improve cognitive functioning scores. Control of positive 
symptoms was well maintained. Treatment-emergent adverse events included dry 
mouth (n = 2) and hallucinations (n = 2). One patient discontinued the study 
because of hallucinations that were considered to be possibly related to 
inadequate antipsychotic therapy. Although preliminary, these results suggest 
modafinil may be an effective and well-tolerated adjunct treatment that improves 
global functioning and clinical condition, and reduces fatigue in patients with 
schizophrenia or schizoaffective disorder. Additional controlled studies are 
warranted.