A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia

Joseph I. Friedman, David N. Adler, Evelyn Howanitz, Philip D. Harvey, Grant Brenner, Humberto Temporini, Leonard White, Michael Parrella

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)349-357
Number of pages9
JournalBiological Psychiatry
Volume51
Issue number5
DOIs
StatePublished - Mar 1 2002
Externally publishedYes

Keywords

  • Acetylcholine
  • Clinical trial
  • Cognitive
  • Donepezil
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

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