Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial.
BACKGROUND
Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine. Clozapine-induced sedation can worsen cognition and impair social and occupational functioning.


OBJECTIVE
To evaluate the efficacy, tolerability, and safety of modafinil for negative symptoms, cognition, and wakefulness/fatigue in DSM-IV-diagnosed schizophrenia patients treated with clozapine.


METHODS
A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007, adding modafinil up to 300 mg/d to stabilized schizophrenia outpatients receiving clozapine. Psychopathology, cognition, and wakefulness/fatigue were assessed with standard rating scales.


RESULTS
Thirty-five patients were randomly assigned to treatment with study drug and included in the analysis. Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo. Modafinil was well tolerated and did not worsen psychosis.


CONCLUSIONS
Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine. However, given our limited power to detect a treatment effect and the clear possibility of a type II error, larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude.


BACKGROUND
clinicaltrials.gov Identifier: NCT00573417.
Freudenreich
Oliver
O
Massachusetts General Hospital Schizophrenia Program, Freedom Trail Clinic, Boston, MA 02114, USA. ofreudenreich@partners.org
Henderson
David C
DC
Macklin
Eric A
EA
Evins
A Eden
AE
Fan
Xiaoduo
X
Cather
Cori
C
Walsh
Jared P
JP
Goff
Donald C
DC
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D003024:Clozapine / Q000008:administration & dosage / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009483:Neuropsychological Tests; D010865:Pilot Projects; D010919:Placebos; D011618:Psychotic Disorders / Q000188:drug therapy / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects
D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D010919:Placebos; D003024:Clozapine; D000077408:Modafinil
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