The mortality risk of conventional antipsychotics in elderly patients: a systematic review of observational studies and randomized trials
HJ Luijendijk,
TA Hulshof, NC de Bruin, SU Zuidema, RWJG Ostelo, AHE Koolman, HJ Luijendijk
Introduction: Numerous cohort studies have found an association between conventional antipsychotics and an increased risk of mortality in elderly patients. Consequently, health authorities have warned against the use of these antipsychotics in patients with dementia. However, terminal illness may have confounded the observational findings. The aim of this study was (1) to critically appraise the results and methods of cohort studies, and (2) to estimate the mortality risk of conventional antipsychotics in randomized placebo-controlled trials.
Methods: Studies were sought in 1) electronic databases; Pubmed, Embase and Cinahl, 2) references of published reviews and meta-analyses, and 3) online trial registers. Cohort studies needed to investigate the mortality risk of new elderly users of conventional antipsychotics. Trials had to compare a conventional antipsychotic to placebo in elderly patients with dementia or (a high risk of) delirium. We abstracted the results from the individual studies and assessed the quality of the methods. We calculated the pooled risk difference (RD) for the trials.
Results: The search yielded 19 cohort studies. Sicker and older patients received conventional antipsychotics more often than new antipsychotics. The risk of dying was especially high in the first month of use, and when haloperidol was administered per injection or in high dosages. Terminal illness was not measured and adjusted for adequately in any study. We also included 17 trials were included (n=2387). Fourteen trials had been performed among patients with dementia, and three were delirium prevention trials. The percentage of deaths for conventional antipsychotics (1.4%) was not higher than that of placebo (1.3%) (RD 0.1%; 95% CI -1.0% to 1.2%).
Conclusions: The observational studies that investigated the mortality risk
in elderly user of conventional antipsychotics did not adjust for terminal
illness. In trials, conventional antipsychotics were not associated with a
higher risk of mortality in patients with dementia or high risk of delirium.
These results strongly question the validity of the observational findings
on which the warning against conventional antipsychotics was based.