Risperidone Eases Some Symptoms of Dementia : Dose of about 1 mg per day brings improvements, but risk of cerebrovascular events rises threefold.


STOCKHOLM – Off-label use of low-dose risperidone is effective in treating the behavioral and psychological symptoms of patients with dementia, but clinicians must balance the drug's usefulness with its increased risk of cerebrovascular events, Peter P. De Deyn, M.D., said at the 12th Congress of the International Psychogeriatric Association.

Most of the available data on the treatment of the behavioral and psychological symptoms of dementia (BPSD) with atypical antipsychotics relates to risperidone, said Dr. De Deyn of the department of neurology at the University of Antwerp (Belgium).

BPSD include verbal and physical aggression, psychotic symptoms, agitation, anxiety, and depression.

Risperidone is approved to treat schizophrenia and bipolar mania associated with bipolar disorder. In May, the Food and Drug Administration opted not to approve risperidone for psychosis of Alzheimer's disease (AD).

In an analysis of pooled data from 1,150 patients in three double-blind, randomized, placebo-controlled trials, Dr. De Deyn and his associates found that 722 patients who had received risperidone had significantly greater improvement from baseline on the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Cohen-Mansfield Agitation Inventory (CMAI) at week 4 through the end of treatment at week 12 than did 428 patients who received placebo (Clin. Neurol. Neurosurg. 2005;107:497–508).

Risperidone patients received a mean dose of 1 mg per day in each trial, said Dr. De Deyn, a speaker and consultant for Janssen Pharmaceutica, which markets risperidone as Risperdal.

In the pooled data set, investigators and caregivers similarly judged risperidone patients as having significantly greater improvement on the Clinical Global Impressions scale than did placebo patients.

At a dose of about 1 mg per day, risperidone also has significantly greater efficacy than haloperidol (Haldol) as shown by results of BEHAVE-AD and CMAI–beginning around week 4–6 of treatment–in two trials of treatment for agitation and aggression in patients with dementia (Neurology 1999;53:946–55; Am. J. Geriatr. Psychiatry 2004;12:509–16).

Psychotic symptoms in patients with psychosis at baseline improved significantly more with risperidone than with placebo in an analysis from one of the trials in the pooled data set that used patients' last available scores as the end point.

In all trials, risperidone did not increase extrapyramidal symptomatology more than placebo. But in trials involving doses of 1 mg of haloperidol per day, the conventional antipsychotic significantly increased the rate of such symptoms.

Risperidone has a statistically significant threefold increase in the relative risk of cerebrovascular adverse events in elderly patients with dementia, including transient ischemic attacks and incapacitating strokes.

The risk appears to be a drug-class phenomenon, since other atypical antipsychotics such as olanzapine (Zyprexa) and aripiprazole (Abilify) also have an increased risk of such events, he said. Risperidone has a warning on its label about the risk of cerebrovascular events in elderly patients with dementia.

A Food and Drug Administration analysis of 17 placebo-controlled trials of atypical antipsychotics in patients with dementia-related psychosis concluded that the drugs were associated with a 60%–70% increase in all-cause mortality, most of which was attributable to infections and cardiovascular disease. But in an analysis of all-cause mortality and risperidone in particular, treatment with risperidone did not contribute to a statistically significant increase in mortality within 30 days of ending treatment, Dr. De Deyn said.

All atypical antipsychotics, including risperidone, have a warning about an increased risk of mortality in elderly patients with dementia.

In a separate poster session, Dr. De Deyn presented a metaanalysis of four double-blind, randomized, controlled trials that examined the effects of risperidone in patients with psychosis of AD.

The metaanalysis included patients from the three trials he pooled to analyze the effects of risperidone on BPSD.

These three 12-week trials indicated that treatment with risperidone significantly improved psychosis subscale scores on the BEHAVE-AD from week 8 onward and on the Clinical Global Impressions scales for severity of illness and change beginning at week 2, compared with placebo (Neurology 1999;53:946–55; J. Clin. Psychiatry 1999;60:107–15; J. Clin. Psychiatry 2003;64:134–43).

But a fourth study included in the metaanalysis showed that risperidone did not prove to be better than placebo after 8 weeks of treating psychosis of AD. Patients in this trial–the results of which are slated to be published in the American Journal of Geriatric Psychiatry–had an average Mini-Mental State Examination score of 13, while in other trials the average was between 6 and 8.

The psychotic symptoms of patients in this 8-week trial were also less pronounced than those of patients in the three other trials, Dr. De Deyn said.

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