A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimers disease
International Journal of Geriatric Psychiatry, 01/11/2011
Clinical Article
Devanand DP et al. – 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.
Methods- In outpatients with AD with symptoms of psychosis or agitation, responders to 20 weeks of haloperidol (0.5–5mg daily) randomized to 24-week, double-blind pilot trial of discontinuation on placebo versus continuation haloperidol
- Phase A response criteria minimum 50% reduction in 3 target symptoms, and improvement on Clinical Global Impression-Change (CGI-C) score for psychosis/agitation
- Phase B relapse criteria required 50% worsening in target symptoms and on CGI-C. α=0.1 was significance criterion in this pilot study
- Of 44 patients, 22 patients responded in Phase A
- 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 1 follow-up visit
- 4 of 10 patients (40%) on continuation haloperidol relapsed compared to 8 of 10 patients on placebo (80%, x 2=3.3, p=0.07)
- In survival analyses, time to relapse was shorter on placebo than haloperidol (x 2=4.1, p=0.04)
