Relapse risk after discontinuation of risperidone in Alzheimer's disease.
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; ClinicalTrials.gov number, NCT00417482.).
Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, New York 10032, USA. dpd3@columbia.edu
D P
DP
Devanand
Jacobo
J
Mintzer
Susan K
SK
Schultz
Howard F
HF
Andrews
David L
DL
Sultzer
Danilo
D
de la Pena
Sanjay
S
Gupta
Sylvia
S
Colon
Corbett
C
Schimming
Gregory H
GH
Pelton
Bruce
B
Levin
D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000187:drug effects; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011595:Psychomotor Agitation / Q000150:complications / Q000188:drug therapy*; D011618:Psychotic Disorders / Q000150:complications / Q000188:drug therapy*; D012008:Recurrence; D012306:Risk; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome
D014150:Antipsychotic Agents; D018967:Risperidone