A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia.
BACKGROUND
Despite the beneficial effects of atypical antipsychotics on cognition, these improvements will not return most schizophrenic patients to normative standards of cognitive functioning. Therefore, other treatments need to be considered. Subtle changes in cholinergic function in schizophrenic patients provide the rationale to test the effectiveness of cholinesterase inhibitors in treating cognitive impairment in schizophrenia.


METHODS
Given this, a 12-week, double-blind, placebo-controlled trial of donepezil (5 mg and 10 mg) as adjunctive treatment to risperidone was conducted in a total of 36 schizophrenic patients.


RESULTS
Neither the 5-mg nor 10-mg dose of donepezil produced significant improvements in any cognitive measure compared with placebo.


CONCLUSIONS
It is possible that nicotinic receptor desensitization produced by chronic tobacco use in these patients rendered their nicotinic receptors refractory to the effects of increased agonist activity produced by donepezil. An alternative treatment is the allosterically potentiating ligands, which enhance the activity of (sensitize) nicotinic receptors in the presence of acetylcholine.
Friedman
Joseph I
JI
Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Adler
David N
DN
Howanitz
Evelyn
E
Harvey
Philip D
PD
Brenner
Grant
G
Temporini
Humberto
H
White
Leonard
L
Parrella
Michael
M
Davis
Kenneth L
KL
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D018967:Risperidone