HealthDay News — Patients with Alzheimer’s disease (AD) and psychosis or agitation-aggression who initially respond to antipsychotic drugs have a high likelihood of relapsing if treatment is discontinued, study results suggest, and may warrant reconsideration of current AD treatment guidelines for U.S. nursing homes.

Among Alzheimer disease patients whose symptoms improved after 16 weeks of open-label treatment with risperidone, those switched to placebo had much higher relapse rates than those who continued therapy with the drug — 60% vs. 33% (P=0.004), Davangere P. Devanand, MD, of Columbia University in New York City, and colleagues reported in the New England Journal of Medicine.

“Our findings suggest that patients with psychosis or agitation-aggression who have a sustained response to antipsychotic treatment for four to eight months have a significantly increased risk of relapse for at least four months after discontinuation, and this finding should be weighed against the risk of adverse effects with continued antipsychotic treatment,” the researchers wrote.

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Currently, long-term antipsychotic use in patients with AD is discouraged due to concerns that the drugs may have adverse effects, and U.S. federal regulations strongly urge nursing homes to discontinue antipsychotics after three to six months of treatment, despite limited supporting evidence from clinical trials.

To better understand how medication discontinuation affects symptom recurrence, Devanand and colleague randomly assigned 110 patients with Alzheimer’s disease and psychosis or agitation-aggression, who had responded to 16 weeks of risperidone treatment to one of three regimens: risperidone therapy for 32 weeks, risperidone therapy for 16 weeks followed by placebo for 16 weeks or placebo for 32 weeks. Primary outcome was the time to relapse of psychosis or agitation.

The researchers found that the relapse rate in the first 16 weeks after randomization was significantly higher in the placebo-only group (24 of 40 patients on placebo vs. 23 of 70 patients in either risperidone group; hazard ratio with placebo=1.94; 95% CI: 1.09 to 3.45; P=0.02).

During the next 16 weeks, the relapse rate was also significantly higher in the group that switched to placebo compared with the group that continued risperidone treatment (48% vs. 15%; H5= 4.88; 95% CI: 1.08-21.98; P=0.02).

Adverse events and mortality did not differ significantly between placebo and risperidone groups, but the researchers warned that between-group comparisons were based on small numbers of patients and are not sufficient to draw meaningful conclusions.

“Additional long-term, controlled trials of antipsychotic treatment and prospective, controlled trials of discontinuation of treatment among patients who have had a response to antipsychotic drugs are needed to inform current regulations that govern clinical practice,” the researchers concluded.


  1. Devanand DP et al. N Engl J Med. 2012; 367:1497-1507.