A randomized, double-blind, placebo-controlled trial of modafinil for negative symptoms in schizophrenia.
OBJECTIVE
Negative symptoms are core features of schizophrenia that are functionally debilitating, associated with poor outcomes, and resistant to existing pharmacotherapies. We performed a randomized, double-blind, placebo-controlled study of modafinil, a medication approved for the treatment of excessive daytime sleepiness, to explore its efficacy as an adjunctive therapy for negative symptoms in schizophrenia.


METHODS
Twenty subjects with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned to double-blind treatment with modafinil or placebo for 8 weeks. The study ran from March 2002 through March 2006. Outcome measures included the Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI) scale, Quality of Life Interview, neurocognitive assessments (California Verbal Learning Test, Degraded Performance-Continuous Performance Test, Trail-Making Test B), and somatic measures (sleep, weight, side effects).


RESULTS
Modafinil treatment was associated with a greater rate (CGI-Improvement [CGI-I] score < or = 3, 7/10 vs. 1/10) and degree (mean CGI-I score, 3.2 vs. 4.1) of global improvement at study endpoint compared with placebo. However, modafinil did not significantly improve global negative symptoms as measured by the total SANS or SANS individual global items. Modafinil did not significantly worsen psycho-pathology (according to the BPRS), compared with placebo, and was well tolerated.


CONCLUSIONS
Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms.
Pierre
Joseph M
JM
Department of Psychiatry, Veterans Administration Greater Los Angeles Healthcare System, and David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, USA. drjoe@ucla.edu
Peloian
John H
JH
Wirshing
Donna A
DA
Wirshing
William C
WC
Marder
Stephen R
SR
D000328:Adult; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy*; D011788:Quality of Life; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil