CARBAMAZEPINE TRIAL IN AGITATED ALZHEIMER'S OUTPATIENTS

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This is a proposal for a random assignment, double-blind, placebo- controlled clinical trial of carbamazepine in 66 probable and possible AD outpatients with clinically significant behavioral disorders. The duration of study is six weeks with a 10 to 7 day screening period (run- in). Subjects will be assessed for efficacy at biweekly intervals using validated instruments by raters blind to treatment condition. A clinical monitor who is open to mediation status will evaluate subjects weekly to enhance safety. Subjects originally assigned to placebo will be offered an open six week trial of medication under similar study conditions. After the six week trial, there will be an open, uncontrolled, continuation phase of 24 week's duration to assess safety, drug autometabolism, and continuing efficacy. Patients will be seen at monthly intervals for follow-up. The objective of this study is to compare carbamazepine (400 to 300 mg/d) to a placebo control in terms of efficacy and side effects in treating agitated AD patients. Measures of efficacy include the Brief psychiatric Rating Scale (BPRS), Clinical Global Improvement Scale (CGI), Hamilton Rating Scale for Depression, Relatives' Assessment of Global Symptomatology-Elderly (RAGS-E), the Physical Self-Maintenance Scale and Instrumental Activities of Daily Living (PSMS/IADL). The primary criterion for clinical response is a greater than or equal to 30% improvement on the agitation factor of the BPRS, and a 'much improved' rating on the CGI. A minimum effect size for carbamazepine is defined (r=0.18). A secondary objective is to replicate a prior observation that platelet 3H-imipramine binding B(max) is decreased, and MAO activity is relatively decreased in Alzheimer's patients with symptomatic behaviors compared to Alzheimer's disease patients without symptomatic behaviors.