title: Benefits of adjunct modafinil in an open-label, pilot study in patients with schizophrenia.
abstract: 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.
authors.affiliation: BMR Healthquest Clinical Trials, San Diego, California 92123, USA. rosenthal@HQtrials.com
authors.forename: Murray H
authors.initials: MH
authors.lastname: Rosenthal
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Bryant
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D018696:Neuroprotective Agents; D000077408:Modafinil