Added donepezil for stable schizophrenia: a double-blind, placebo-controlled trial

Abstract

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).

Efficacy and Safety of Donepezil in Patients with Schizophrenia or Schizoaffective Disorder: Significant Placebo/Practice Effects in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

“…In this population of stable schizophrenia/schizoaffective patients maintained on selected second-generation antipsychotics, donepezil appeared to be as safe and as welltolerated as placebo, in agreement with a previous doubleblind, placebo-controlled study in schizophrenic patients (Freudenreich et al, 2005) and studies in AD patients (Pratt et al, 2002). In particular, the rate of anticipated cholinomimetic AEs, such as diarrhea and nausea, was less frequent than observed in studies with patients who received donepezil 10 mg/day for the treatment of AD dementia.…”

“…The results of this study reinforce the findings of some of the previously reported double-blind, placebo-controlled trials in smaller samples, which suggested that adjunctive donepezil therapy does not significantly improve cognitive impairment in moderately ill patients with schizophrenia or schizoaffective disorder maintained on antipsychotic medication (Freudenreich et al, 2005;Friedman et al, 2002;Tugal et al, 2004;Fagerlund et al, 2007). Whether this conclusion applies to other AChEIs remains to be demonstrated.…”

“…While two case studies and a small, open-label study revealed some cognitive improvement with donepezil treatment (Buchanan et al, 2003;MacEwan et al, 2001;Risch et al, 2001), four double-blind, placebocontrolled trials did not (Freudenreich et al, 2005;Friedman et al, 2002;Tugal et al, 2004;Fagerlund et al, 2007). It is likely that the latter trials were not sufficiently powered to detect a treatment effect on cognition, since no study enrolled more than 36 patients.…”

Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats

“…To date, however, the data collected in the relatively small number of clinical studies that have been designed to evaluate the potential cognitive benefits of AChEIs in schizophrenia have been equivocal. For example, the beneficial effects of donepezil or rivastigmine on cognition in schizophrenics as add-on treatments to antipsychotics observed in small preliminary investigations, open-label studies and case reports (e.g., Buchanan et al, 2003;Stryjer et al, 2003;Lenzi et al, 2003) were not confirmed in larger randomized, doubleblind, and placebo controlled studies (see Friedman et al, 2002;Freudenreich et al, 2005;Sharma et al, 2006). In the case of galantamine, there are also several small studies that indicate a potential benefit to schizophrenic patients including a recent randomized, doubleblind clinical trial (N=8) where the AChEI improved short-term memory and attention in schizophrenic or schizoaffective patients who were stabilized on risperidone (Schubert et al, 2006).…”

Towards a muscarinic hypothesis of schizophrenia

“…132 Likewise, the addition of up to 10 mg of donepezil to ongoing antipsychotic treatment did not improve cognitive or psychopathological measures in 36 subjects with schizophrenia. 133 Fewer studies have yet been conducted with the other cholinesterase inhibitors. A 12-month study using low-dose rivastigmine, another cholinesterase inhibitor, showed a significant improvement in quality of life and neuropsychological measures in subjects with schizophrenia with predominant residual symptoms.…”