Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials.

The burden of de-mentia is staggering — over 8% of the population over the age of 65 is affected 1 — and behavioural disturbances that often accompany dementia (including physical aggression, hallucinations , wandering, yelling, throwing and vocalizations) 2 are distressing for caregivers and patients alike. 3 Acetyl-cholinesterase inhibitors may play a role in slowing the cognitive decline of patients with Alzheimer's disease, 4 but low-dose therapy with antipsychotic agents (including risperidone) is often used to control behavioural problems. 5 However, a recent analysis by the drug's manufacturer of trials involving patients with dementia suggests that the use of risperidone may be associated with increased rates of cerebrovascular adverse events, including stroke and transient ischemic attacks, when compared with placebo. 6 In 4 placebo-controlled trials lasting 1–3 months and involving more than 1200 patients with Alzheimer's disease or vascular demen-tia, cerebrovascular adverse events were twice as common in the risperidone-treated group (4%) as in the placebo group (4% v. 2%) (Table 1). A further search of international databases of postmarketing adverse events revealed 37 cases (1 in Canada) of such events in elderly dementia patients taking risperi-done, of which 16 (43%) were fatal. 6 The drug: Although the exact mechanism of action of risperidone is unknown , the drug blocks receptors in the dopaminergic, adrenergic and hist-aminergic neurotransmitter systems as well as those in the serotonin system that may play a role in agression. Like other atypical antipsychotic agents, risperidone is a popular first-line agent for psychotic disorders because it is effective (especially for negative symptoms) and is associated with fewer extrapyramidal adverse effects than are traditional antipsychotic drugs. 7 Risperidone, at doses higher than those used in dementia, appears to cause diabetes, worsened lipid profiles and obesity in some patients, 10 but any relation between these adverse effects and risperidone-associated cerebrovas-cular adverse events is unclear. Risperi-done should be used with caution in patients with seizure disorders and avoided in states of dehydration and hypotension. What to do: Dementia is a difficult burden for patients and caregivers, 11 but the degree to which a behaviour is a problem depends greatly on a caregiver's ability to tolerate the problem. Given dementia's prevalence and its sufferer's susceptibility to medication-related adverse events, nonpharmacologic measures are often preferable. Education of family members about natural exacerba-tions of disruptive behaviours in the early evening (" sun-downing ") is important , and the " knee-jerk " initiation …