Antipsychotics and AD Don't Mix, Increase Risk of Death

Patients who suffer from Alzheimer's Disease and receive antipsychotics have a higher risk of death than their comparable cohorts who are not given these medications, according to a new study published online in The Lancet Neurology. Using the drugs for a short period can provide modest benefits for some patients but can cause side effects like sedation, chest infections, decline in brain function, stroke, and Parkinson-like symptoms.

Participants were randomly assigned to continue with their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluoperazine, or risperidone) for 12 months or to switch their medication to an oral placebo. The primary outcome was mortality at 12 months.

For their placebo-controlled, parallel, two-group treatment discontinuation trial, researchers had 165 patients randomized (83 to continue antipsychotic treatment and 82 to placebo), of whom 128 (78 percent) started treatment (64 continued with their treatment and 64 received placebo). A reduction was seen in the survival of patients who continued to receive antipsychotics compared with those who received placebo. The cumulative probability of survival throughout the 12 months was 70 percent (95% CI 58-80%) in the continue treatment group against 77 percent (64-85%) in the placebo group for the mITT population.

The study authors say, "Kaplan-Meier estimates of mortality for the whole study period showed a significantly increased risk of mortality for patients who were allocated to continue antipsychotic treatment compared with those allocated to placebo (mITT log rank p=0.03; ITT p=0.02)." They found the hazard ratio for the mITT group was 0.58 (95% CI 0.35 to 0.95) and 0.58 (0.36 to 0.92) for the ITT population. "The more pronounced differences between groups during periods of follow up longer than 12 months were evident at specific timepoints (24-month survival: 46 percent versus 71 percent; 36-month survival: 30 percent versus 59 percent)," they write.

Psychosis of AD is characterized by delusions or hallucinations and may be associated with agitation, negative symptoms or depression.¹ There are no psychotropic medications that are approved by the FDA for the treatment of psychosis of AD.

1. Madhusoodanan S, Shah P. Management of psychosis in patients with Alzheimer's disease: focus on aripiprazole. Clin Interv Aging. 2008;3(3):491-501.