Antipsychotic drug quandary for Alzheimer’s patients

By Eleanor McDermid, Senior medwireNews Reporter

Stopping treatment with risperidone to limit side effects risks the return of psychosis or agitation in patients with Alzheimer's disease (AD) who have been taking the drug to suppress such symptoms, research shows.

Patients who were switched to placebo had twice the risk for relapse of those who remained on risperidone, show the findings published 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 4 to 8 months have a significantly increased risk of relapse for at least 4 months after discontinuation, and this finding should be weighed against the risk of adverse effects with continued antipsychotic treatment," say the researchers.

Reported adverse effects include sedation, extrapyramidal signs, tardive dyskinesia, weight gain, and the metabolic syndrome, say D Devanand (New York State Psychiatric Institute, New York, USA) and co-workers. Thus, physicians are advised to discontinue antipsychotics as early as practicable.

But the researchers note: "Evidence from controlled trials in support of this long-standing regulation is very limited."

They designed the Antipsychotic Discontinuation in Alzheimer's Disease (ADAD) trial to address this. It included 180 AD patients with psychosis or agitation-aggression who received open-label risperidone for 16 weeks.

In all, 112 (62%) patients responded to treatment; however, the team observes that "risperidone was not highly effective in achieving and maintaining a reduction in symptoms of psychosis and agitation in patients with Alzheimer's disease."

Of the patients with a response, 110 entered the second phase of the trial and were randomly assigned to receive continued risperidone treatment (n=70) or placebo (n=40). During the first 16 weeks of this phase, 33% of patients still taking risperidone relapsed, but the rate was even higher in the placebo group, at 60%, equating to nearly a twofold increased relapse risk. The crude relapse rates were 6.5 and 3.0 per 100 patient-weeks, respectively.

The patients still taking risperidone were then re-randomized, so that 27 were switched to placebo. Over an additional 16 weeks of treatment, the relapse rate was 48% among these patients versus 15% among those who continued to take risperidone, giving nearly a fivefold risk increase.

Adverse effects did not significantly differ between patients in the risperidone and placebo groups during any phase, although the researchers note that the trial was too small to assess between-group differences in serious adverse events. During the open-label phase, there was an overall significant increase in extrapyramidal (parkinsonian) signs.

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