Clozapine in Elderly Psychiatric Patients: Tolerability, Safety, and Efficacy Y. Barak, N. Wittenberg, S. Naor, D. Kutzuk, and A. Weizman Psychotic disorders in the elderly are frequent, of multiple etiologies, and little researched. With the advent of "atypical" neuroleptics, their role in treating elderly psychiatric patients needs to be investigated. Clozapine is widely used; however, its usa is common in the elderly whose psychosis is a feature of neurologi- cal morbidity (Parkinson's disease, dementia, etc.), making it difficult to ascertain the safety, tolerability, and efficacy in psychiatric disorders in late life. The aim of the present review is to evaluate clozapine's effect in elderly psychiatric patients with no neurologi- cal comorbidity. A computerized literature search (MedLine 1966 to 1997) revealed 133 patients fulfilling said criteria. Fifteen patients had side effects and/or adverse events during treatment; nine of these were receiving a dosage greater than 100 mg clozapine daily. In 19 patients, treatment was discontinued, three due to noncompliance and 16 due to side effects. In seven patients, leukopenia/agranulocytosis was reported. The majority of side effects (27 of 34) and treatment discontinuations were within the first 90 days of treatment. Although efficacy is difficult to compare across studies because of differing methods of evaluation, the great majority of patients showed moderate to marked improvement of psychotic fea- tures. The reported effectiveness in patients able to continue treatment for extended periods is significant. Thus, clozapine at a relatively low mean dose (134 mg daily) seems to be safe, tolerated, and effective in elderly psychiatric patients. Agranulocytosis is more frequent than in younger adults and should be moni- tored carefully. Copyright© 1999by W.B. Saunders Company A LTHOUGH PSYCHOTIC DISORDERS and schizophrenia, in particular, are the most disabling psychiatric conditions affecting young adults, their prevalence and impact in the elderly are considerable. 1-3 The changing demographics of Western countries require a widening of research in geriatric psychiatry. 4 However, recent reviews high- light the fact that this need is not being fulfilled.1 The limited research on "elderly" individuals (i.e., those aged 65 years and older) with schizophrenia coupled with decades of treatment based almost exclusively on postsynaptic D2 receptor blockade has generated excitement and interest with the introduction of novel ("atypical") antipsychot- ics.5, 6 Clozapine is an atypical antipsychotic that is widely used and researched. It has superior efficacy to chlorpromazine, haloperidol, and fluphenazine in treatment-resistant schizophrenic patients7,8 and significantly improves the quality of life and social functioning.9 In the United States, Europe, and Israel, the approved indication for the use of clozapine is treatment-resistant schizophenia. 1° In From the Psychogeriatric Department, Abarbanel Mental Health Center, Bat-Yam; Faculty of Agriculture, Hebrew Univer- sity, Rehovot; Kaplan Medical Center, Rehovot; Ben Gurion University, Beer-Sheva; and Geha Mental Health Center, Petach- Tiquva, Israel. Address reprint requests to Y. Barak, M.D., Abarbanel Mental Health Center, 15, Keren Kayemet Blvd, 59100 Bat-Yam, Israel. Copyright © 1999 by W.B. Saunders Company 0010-440X/99/4004-000751 O. 00/0 the elderly, clozapine has been used for this indica- tion in several studies. 11-18 However, in clinical practice, clozapine is studied and used widely for a variety of psychotic and behavioral conditions and organic disorders. Among the various published reports, clozapine has been used in the elderly in the following conditions: tardive dyskinesia (TD), 11,19 behavioral disruption with psychosis,2°,21 socially disturbing behavior in demented patients, 22 delusional disorders, 23 schizoaffective disorders,24 refractory depressionY bipolar affective disor- ders,26,27Parkinson's disease, 28,29Huntington's dis- ease, 3°,31and essential tremor.32 As comorbid neuro- logical conditions may affect treatment parameters, there is a need to evaluate clozapine use in "pure" psychiatric disorders. The aim of the present analysis is to evaluate the tolerability, safety, and efficacy of clozapine in elderly psychiatric patients without comorbid neu- rological conditions. METHOD A computer literature search (MedLine) using the subhead- ings clozapine, aged, and elderly was performed for the period 1966 to 1998. We present an analysis of the results described in these studies according to the methodology: (1) nine case reports (16 subjects), (2) four retrospective chart review-based reports (56 subjects), (3) a nonspecific chart review of 51 subjects aged 14 to 89 years, and (4) two open-label studies (13 subjects). A brief description of each study will be followed by an analysis of safety, tolerability, and efficacy. In addition, the authors' clinical experience will be briefly described. 320 ComprehensivePsychiatry, Vol. 40, No. 4 (July/August), 1999: pp 320-325