Original ArticlesEffects of Donepezil Adjunctive Treatment to Ziprasidone on Cognitive Deficits in Schizophrenia: A Double-blind, Placebo-Controlled StudyFagerlund, Birgitte PhD*; Søholm, Bettina MD*; Fink-Jensen, Anders DMSc†; Lublin, Henrik DMSc‡; Glenthøj, Birte Y. DMSc*‡Author Information *Department of Psychiatry E, Center for Neuropsychiatric Schizophrenia Research, Bispebjerg University Hospital, †Department of Psychiatry, Rigshospitalet University Hospital, and the ‡Psychiatric University Centre Glostrup, Copenhagen, Denmark. Address correspondence and reprint requests to Birgitte Fagerlund, PhD, Adult Psychiatric Department E, Center for Neuropsychiatric Schizophrenia Research, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark; E-mail: firstname.lastname@example.org Supported by an unrestricted grant from Pfizer Denmark A/S. Clinical Neuropharmacology: January-February 2007 - Volume 30 - Issue 1 - p 3-12 doi: 10.1097/01.WNF.0000240940.67241.F6 Buy Metrics Abstract The objective of this study was to examine the effects of adjunctive treatment with the acetylcholinesterase inhibitor, donepezil, on cognitive deficits and psychopathology in schizophrenic patients treated with the antipsychotic, ziprasidone. The design of the study was double blind, placebo controlled, and longitudinal. Patients were treated with ziprasidone for 8 weeks, thereafter randomized to 4 months of double-blind adjunctive treatment with either donepezil (dose, 5-10 mg) or placebo. The severity of psychopathology (PANSS) and the cognitive deficits were examined at baseline and after 4 months. A total of 21 schizophrenic patients were enrolled, of whom 11 patients completed the trial (donepezil, n = 7; placebo, n = 4). There were no within- or between-group differences in changes on the Positive and Negative Syndrome Scale scores or a global cognitive score. Within-group improvements (all at trend level P = 0.07) were seen in the placebo group on Trail-Making Test B, immediate verbal recall, and set-shifting errors. The donepezil group showed a significant deterioration on planning efficiency (P = 0.04). Between-group differences were found between the lack of improvement in immediate verbal recall in the donepezil group and the improvement in the placebo group (P = 0.02), and between the deterioration of planning efficiency in the donepezil group and the stability in the placebo group (trend level, P = 0.07). Linear regression analyses showed that neither baseline psychopathology scores, baseline levels of cognitive deficits, nor psychopathology changes over time accounted for these changes in cognitive scores. The study found no evidence of improved cognition after treatment with donepezil, although the conclusions that can be drawn are limited by the small sample size. © 2007 Lippincott Williams & Wilkins, Inc.