Clinical Question: Do atypical antipsychotic medications increase the risk of death for patients with dementia?

Setting: Various (meta-analysis)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: Antipsychotic medications commonly are used to treat neuropsychiatric symptoms of depression, including aggression, agitation, and delusions. Newer atypical antipsychotic medications, including risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and aripiprazole (Abilify) generally have replaced first-generation anti-psychotic medications such as haloperidol (Haldol) and thioridazine (Mellaril). However, controversy exists regarding the risk of increased mortality associated with the use of atypical antipsychotic medications in older patients with dementia.

The investigators searched MEDLINE, the Cochrane Controlled Trials Register, conference programs and proceedings, and pharmaceutical manufacturer databases to identify randomized controlled double-blind trials comparing orally administered antipsychotics with placebo in older patients with dementia. One individual abstracted all data and another checked the results. Both investigators reviewed data discrepancies to ensure accuracy. Fifteen trials fulfilled inclusion criteria: 3,353 patients were randomized to active medications and 1,757 to placebo. Most of the patients had Alzheimer’s disease (87 percent) and were women (70 percent). Monitoring occurred for an average of eight to 12 weeks. A total of 118 deaths occurred in the atypical antipsychotic medication groups compared with 40 in the placebo groups (3.5 versus 2.3 percent; number needed to harm = 100; 95% confidence interval, 53 to 1,000). Results were similar across the various trials. A sensitivity analysis did not find evidence for differential risk for individual medications (including the first-generation antipsychotics), severity of symptoms, or diagnosis. A formal analysis found no evidence of publication bias.

Bottom Line: The use of atypical antipsychotic medications for even short periods (less than eight to 12 weeks) is associated with a significantly increased risk of death. Antipsychotic medications should be used only in individual situations where there is an identifiable risk of harm and when alternate therapies have failed. (Level of Evidence: 1a)