A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease
Article first published online: 28 DEC 2010
Copyright © 2010 John Wiley & Sons, Ltd.
International Journal of Geriatric Psychiatry
Volume 26, Issue 9, pages 937–943, September 2011
How to Cite
Devanand, D.P., Pelton, G. H., Cunqueiro, K., Sackeim, H. A. and Marder, K. (2011), A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease. Int. J. Geriat. Psychiatry, 26: 937–943. doi: 10.1002/gps.2630
- Issue published online: 11 AUG 2011
- Article first published online: 28 DEC 2010
- Manuscript Accepted: 2 AUG 2010
- Manuscript Received: 30 JUN 2010
- NIH. Grant Numbers: R01MH55735, R01 AG17761
- Alzheimer's disease
In patients with Alzheimer's disease (AD) with psychosis or agitation that respond to haloperidol treatment, to evaluate the risk of relapse following discontinuation.
In outpatients with AD with symptoms of psychosis or agitation, responders to 20 weeks of haloperidol (0.5–5 mg daily) were randomized to a 24-week, double-blind pilot trial of discontinuation on placebo versus continuation haloperidol. Phase A response criteria were minimum 50% reduction in three target symptoms, and improvement on the Clinical Global Impression-Change (CGI-C) score for psychosis/agitation. Phase B relapse criteria required 50% worsening in target symptoms and on the CGI-C. α = 0.1 was the significance criterion in this pilot study.
Of 44 patients, 22 patients responded in Phase A. The sum score of target symptoms, and Brief Psychiatric Rating Scale (BPRS) psychosis and hostile suspiciousness factor scores, decreased in Phase A (p's < 0.001). Extrapyramidal signs increased in Phase A (p < 0.01). Of 22 responders, 21 patients entered Phase B, and 20 had at least one follow-up visit. Four of 10 patients (40%) on continuation haloperidol relapsed compared to eight of 10 patients on placebo (80%, χ2 = 3.3, p = 0.07). In survival analyses, time to relapse was shorter on placebo than haloperidol (χ2 = 4.1, p = 0.04).
Haloperidol open treatment was efficacious, and relapse was greater on placebo than with haloperidol continuation. In patients with AD who have psychosis or agitation and respond to antipsychotic medication, the increased risk of relapse after discontinuation needs to be weighed against the side effects associated with continuing the medication. Copyright © 2010 John Wiley & Sons, Ltd.