The efficacy and side effects of low dose (0.5 to 0.75 mg daily) versus traditional dose (2 to 3 mg daily) oral haloperidol treatment of psychosis and behavioral disturbance will be evaluated in a random assignment double-blind placebo controlled study of outpatients with probable Alzheimer's disease (NINCDS-ADRDA criteria). In addition to standardized rating scales and the tracking of target symptoms, specific strategies will be used to overcome difficulties in following symptom profiles in demented outpatients. The side effects associated with these three treatment conditions (low dose haloperidol, traditional dose haloperidol and placebo) will be assessed in three areas: somatic side effects, activities of daily life, and level of cognitive functioning, the latter examined with detailed neuropsychological evaluation. Plasma haloperidol and serum prolactin levels will be determined to evaluate their utility in monitoring neuroleptic treatment at these dose ranges. Pilot study data indicate that while haloperidol treatment, in doses that are commonly used, is effective in controlling psychosis and behavioral disturbance in some patients with Alzheimer's disease (AD), it produces significant extrapyramidal side effects and may result in measurable cognitive deterioration within a few weeks. The three treatment conditions, low dose haloperidol, traditional dose haloperidol and placebo, will be compared in a random assignment parallel group double-blind placebo-controlled phase, with the aim of finding an effective dose of haloperidol that produces minimal side effects. Pilot study data also suggest that changes in symptomatology and cognition may persist at least four weeks after haloperidol discontinuation. In the proposed study, after the parallel group treatment phase, patients on active drug will enter a subsequent double-blind placebo phase to determine drug discontinuation effects. There is a high prevalence of psychosis and behavioral distrubance in AD, and a large number of these patients are treated with neuroleptics. Given the inadequate data on the efficacy and side effects of neuroleptic treatment in this disorder, this study will help determine the risk/benefit ratio of different dosage conditions of haloperidolin in the treatment of psychosis and behavioral disturbance in AD.
| Devanand, D P; Levy, S R (1995) Neuroleptic treatment of agitation and psychosis in dementia. J Geriatr Psychiatry Neurol 8 Suppl 1:S18-27 |
