Freudenreich_2005_Psychopharmacology.(Berl)_181_358

RATIONALE: Schizophrenia is a disorder with cognitive deficits that could stem from cholinergic dysfunction. OBJECTIVES: Our aim was to examine if donepezil administered to stable, medicated outpatients with schizophrenia improves cognition and psychopathology.
METHODS: We conducted a double-blind placebo-controlled trial of donepezil up to 10 mg/day added for 8 weeks to ongoing antipsychotic treatment in 36 typical community-treated schizophrenia patients not selected for cognitive impairment.
RESULTS: Donepezil did not improve measures of cognition or psychopathology. It was well tolerated. CONCLUSION: Consistent with other studies, addition of donepezil to stable patients with schizophrenia did not improve cognition or measures of psychopathology. This result does not support the hypothesis that residual symptoms and cognitive problems result from a cholinergic deficit that can be remedied by an acetylcholinesterase inhibitor. A donepezil add-on strategy might make sense in selected schizophrenia cases where a pathological process is known to affect cholinergic neurons (e.g., history of head injury or comorbid dementia).