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Relapse risk after discontinuation of risperidone in Alzheimer’s disease


Devanand, D. P., Mintzer, Jacobo, Schultz, Susan K., Andrews, Howard F., Sultzer, David L., de la Pena, Danilo, Gupta, Sanjay, Colon, Sylvia, Schimming, Corbett, Pelton, Gregory H., Levin, Bruce


The New England Journal Of Medicine, Volume: 367, No.: 16, Pages.: 1497-1507

Year of Publication



Background: Among patients with Alzheimer’s disease who have had a response to antipsychotic medication for psychosis or agitation-aggression, the risk of a recurrence of symptoms after discontinuation of the medication has not been established.; Methods: Patients with Alzheimer’s disease and psychosis or agitation-aggression received open-label treatment with risperidone for 16 weeks. Those who had a response to risperidone therapy were then randomly assigned, in a double-blind fashion, to one of three regimens: continued risperidone therapy for 32 weeks (group 1), risperidone therapy for 16 weeks followed by placebo for 16 weeks (group 2), or placebo for 32 weeks (group 3). The primary outcome was the time to relapse of psychosis or agitation.; Results: A total of 180 patients received open-label risperidone (mean dose, 0.97 mg daily). The severity of psychosis and agitation were reduced, although there was a mild increase in extrapyramidal signs; 112 patients met the criteria for response to treatment, of whom 110 underwent randomization. In the first 16 weeks after randomization, the rate of relapse was higher in the group that received placebo than in the groups that received risperidone (60% [24 of 40 patients in group 3] vs. 33% [23 of 70 in groups 1 and 2]; P=0.004; hazard ratio with placebo, 1.94; 95% confidence interval [CI], 1.09 to 3.45; P=0.02). During the next 16 weeks, the rate of relapse was higher in the group that was switched from risperidone to placebo than in the group that continued to receive risperidone (48% [13 of 27 patients in group 2] vs. 15% [2 of 13 in group 1]; P=0.02; hazard ratio, 4.88; 95% CI, 1.08 to 21.98; P=0.02). The rates of adverse events and death after randomization did not differ significantly among the groups, although comparisons were based on small numbers of patients, especially during the final 16 weeks.; Conclusions: In patients with Alzheimer’s disease who had psychosis or agitation that had responded to risperidone therapy for 4 to 8 months, discontinuation of risperidone was associated with an increased risk of relapse. (Funded by the National Institutes of Health and others; number, NCT00417482.).;

Bibtex Citation

@article{Devanand_2012, doi = {10.1056/nejmoa1114058}, url = {}, year = 2012, month = {oct}, publisher = {New England Journal of Medicine ({NEJM}/{MMS})}, volume = {367}, number = {16}, pages = {1497--1507}, author = {D.P. Devanand and Jacobo Mintzer and Susan K. Schultz and Howard F. Andrews and David L. Sultzer and Danilo de la Pena and Sanjay Gupta and Sylvia Colon and Corbett Schimming and Gregory H. Pelton and Bruce Levin}, title = {Relapse Risk after Discontinuation of Risperidone in Alzheimer{textquotesingle}s Disease}, journal = {New England Journal of Medicine} }


adverse effects, aged, aged, 80 and over, aggression, agitation, alzheimer disease, antipsychotic agents, complications, doubleblind method, drug effects, drug therapy, female, humans, male, or, psychology, psychomotor agitation, psychosis, psychotic disorders, recurrence, risk, risperidone, substance withdrawal syndrome, therapeutic use

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Antipsychotics and antidepressants