There is considerable incentive to develop new treatment strategies that effectively target cognitive deficits in
schizophrenia. One of the theoretically promising novel treatment candidates is
acetylcholinesterase inhibitors that increase the synaptic levels of
cholinergic, nicotinic, and
muscarinic receptor activity. The purpose of this study was to assess the efficacy of
donepezil as an adjuvant agent in the treatment of chronic
schizophrenia in particular for
cognitive impairments. This investigation was a 12-week, double-blind study of parallel groups of patients with stable chronic
schizophrenia. Thirty patients were recruited from inpatient and outpatient departments, age ranging from 22 to 44 years. All participants met DSM-IV-TR. diagnostic criteria for
schizophrenia. To be eligible, patients were required to have been treated with a stable dose of
risperidone as their primary
antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive
donepezil (10 mg/day) or placebo, in addition to
risperidone (4-6 mg/day). Clinical psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS). Cognition was measured by a cognitive battery. Patients were assessed by a psychiatrist at baseline and after 8, and 12 weeks after the medication started. The PANSS scores and cognitive performance were used as the outcome measures. The
donepezil group had significantly greater improvement in the negative symptoms over the 12-week trial. There were no differences between the
donepezil and placebo groups on any neurocognitive assessments at endpoint (week 12). The present study indicates
donepezil as a potential adjunctive treatment strategy for negative symptoms of chronic
schizophrenia.