Beneficial Effect of Donepezil Augmentation for the Management of Comorbid Schizophrenia and Dementia *Rafael Stryjer, *†Rael D. Strous, *†Faina Bar, †‡Edith Werber, *Ginette Shaked, *Yosef Buhiri, *†Moshe Kotler, †§Abraham Weizman, and †‡Jose M. Rabey *Beer-Yaakov Mental Health Center, Beer-Yaakov; †Sackler Faculty of Medicine, Tel Aviv University, Ramat-Aviv; ‡Neurology Department, Assaf Harofeh Medical Center; and §Geha Mental Health Center, Petah-Tikva, Israel Summary: Comorbid schizophrenia and dementia is a common clinical phenomenon; however, management of the coexisting illnesses remains incomplete. Donepezil, a cho- linesterase inhibitor, may be beneficial for the management of symptoms of Alzheimer’s disease, a disease in which cholinergic pathways in the cerebral cortex and basal fore- brain are well known to be compromised. Furthermore, impaired cognition in elderly schizophrenic patients has been observed to be more than two thirds; however, there are no published controlled studies reporting the use of cholinesterase inhibitors in the man- agement of schizophrenia in patients with associated dementia. In this study, six patients with chronic schizophrenia and comorbid dementia were administered donepezil, 5 mg, in single-blind fashion as augmentation to their standard antipsychotic medication for a 4-week period. Patients were evaluated with the Mini Mental State Examination (MMSE); Alzheimer’s Disease Assessment Scale, Cognitive subscale; Positive and Negative Symptom Scale (PANSS); and the Clinical Global Impression (CGI) scales. A significant improvement was noted in MMSE scores (p < 0.01) and for CGI scores (p < 0.01). In addition, three patients demonstrated improvement on the PANSS. Donepezil appears to be an effective treatment for the management of symptoms of dementia ac- companying patients with comorbid schizophrenia and dementia. Since cholinergic dys- function may be present in some patients with schizophrenia, the authors’ findings fur- ther demonstrate the possibility that this disorder may be managed with cholinergic medications as augmenting agents, at least in this specific subpopulation of patients with comorbid dementia. To confirm the findings of this preliminary trial, further investiga- tion is mandated with a larger sample of subjects in the context of a double-blind medi- cation trial. Key Words: Schizophrenia—Dementia—Donepezil The comorbid expression of schizophrenia and de- mentia is frequently observed in clinical practice. While pharmacologic management of the separate con- ditions is improving, adequate therapy for the coexist- ing illnesses remains lacking. Furthermore, clinically significant cognitive impairments, including deficits in attention, memory, verbal skills, motor skills, and ex- ecutive function, occur in approximately 85% of schizophrenic patients (1). This cognitive impairment often occurs at a very early age, frequently before any emergent overt clinical symptomatology (2,3), and in many patients, it worsens during the course of illness to the extent of dementia-like proportions (4,5). Interest- ingly, while it may be considered that cognitive dys- function resulting in dementia later in life may be in- creased in those with schizophrenia, the incidence of Alzheimer’s-type dementia in elderly schizophrenic patients is not known to be different from that of the general elderly population and, in fact, may be even less (6,7). Donepezil is a centrally active relatively specific acetylcholinesterase inhibitor and has been shown to be beneficial for the management of symptoms of memory and cognitive dysfunction in patients with mild to mod- erately severe Alzheimer’s disease (8). It is relatively well tolerated with few adverse effects. In addition, more recent observation suggests that neuropathology of Alzheimer’s dementia does not have to be present for cognitive enhancement with donepezil to occur (9). Al- Address correspondence and reprint requests to Dr. Rael Strous, Beer Yaakov Mental Health Center, P.O. Box 1, Beer Yaakov 70350, Israel; E-mail: raels@post.tau.ac.il. Clinical Neuropharmacology Vol. 26, No. 1, pp. 12–17 © 2003 Lippincott Williams & Wilkins, Inc., Philadelphia 12