A 12-week, double-blind, placebo-controlled trial of donepezil as an adjunct to haloperidol for treating cognitive impairments in patients with chronic schizophrenia

Abstract

To study the effects of acetylcholinesterase inhibitors (AChEIs) in the management of cognitive impairments in patients with schizophrenia, we investigated the effects of 12 weeks of adjunctive therapy with donepezil on their cognitive impairments. Twenty-four subjects stabilized on haloperidol treatment (5-30 mg/day) for a minimum of 3 months were entered into a double-blind, placebo-controlled trial of donepezil as an adjunctive treatment. Subjects were randomly assigned under double-blind conditions to receive either 5 mg/day donepezil (N = 12) or pLacebo (N = 12) for 12 weeks. The subjects were evaluated at baseline, and after 4, 8, and 12 weeks using the Korean version of Mini Mental State Examination (K-MMSE), Brief Psychiatric Rating Scale (BPRS), and standard neuropsychological assessment. The K-MMSE scores improved significantly (p < 0.05) but the BPRS scores did not improve significantly in patients given donepezil; subjects showed slight improvement in several cognitive measures. At the end of the study, the difference in the mean K-MMSE scores between the donepezil and placebo groups approached statistical significance (p = 0.056). Of the several domains of cognitive functions assessed, verbal recognition and visual recall memory improved significantly (p < 0.05). But donepezil did not affect scores in the executive function tests. Our findings support a potential positive effect of AChEIs in the management of cognitive impairments in patients with chronic schizophrenia. Further studies with large subjects are needed to confirm our findings.