Donepezil for negative signs in elderly patients with schizophrenia: an add-on, double-blind, crossover, placebo-controlled study.
OBJECTIVE
Cognitive impairment and negative signs are common in patients with schizophrenia. Up to 35% of elderly patients with schizophrenia fulfill the diagnostic criteria of dementia. Donepezil inhibits cholinesterase, thus enhancing cholinergic neurotransmission. We tested the efficacy of donepezil in elderly patients with chronic schizophrenia and severe cognitive impairment.


METHODS
Following baseline assessment, patients were randomly assigned to receive either donepezil or placebo. The dose was 5 mg daily for the first week and 10 mg for an additional 11 weeks. The procedure was repeated using the crossover compound. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI) and Alzheimer Disease Assessment Scale - Cognitive subscale (ADAS-Cog) were used to assess the severity of symptoms, cognitive status and intervention effects.


RESULTS
Twenty subjects were enrolled (15 females, five males), mean age 70.2 years (SD 6.5) and mean duration of disease 38.5 years (SD 9.3). A modest treatment effect was found for both placebo and donepezil treatment periods. No crossover effect was found. No statistical differences were demonstrated between the two treatment groups (CGI p = 0.37, PANSS p = 0.71, ADAS-Cog p = 0.86). Two patients died during the study period due to unrelated causes and one patient discontinued participation due to increased agitation.


CONCLUSIONS
Donepezil does not seem to improve negative signs and cognitive impairment in elderly patients with chronic schizophrenia.
Mazeh
D
D
Psychogeriatric ward, Abarbanel Mental Health Center, Bat-Yam and the Sackler School of Medicine, Tel-Aviv University, Israel. mazehdor@netvision.net.il
Zemishlani
H
H
Barak
Y
Y
Mirecki
I
I
Paleacu
D
D
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002908:Chronic Disease; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D015897:Comorbidity; D018592:Cross-Over Studies; D003704:Dementia / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000077265:Donepezil; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil