The Mortality Risk of Conventional Antipsychotics in Elderly Patients: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.
BACKGROUND
Numerous observational studies have reported an increased risk of mortality for conventional antipsychotics in elderly patients, and for haloperidol in particular. Subsequently, health authorities have warned against use of conventional antipsychotics in dementia. Experimental evidence is lacking.


OBJECTIVE
To assess the mortality risk of conventional antipsychotics in elderly patients with a meta-analysis of trials.


METHODS
Original studies were identified in electronic databases, online trial registers, and hand-searched references of published reviews. Two investigators found 28 potentially eligible studies, and they selected 17 randomized placebo-controlled trials in elderly patients with dementia, delirium, or a high risk of delirium. Two investigators independently abstracted trial characteristics and deaths, and 3 investigators assessed the risk of bias. Deaths were pooled with RevMan to obtain risk differences and risk ratios.


RESULTS
Data of 17 trials with a total of 2387 participants were available. Thirty-two deaths occurred. The pooled risk difference of 0.1% was not statistically significant (95% confidence interval (CI) -1.0%-1.2%). The risk ratio was 1.07 (95% CI 0.54-2.13). Eleven of 17 trials tested haloperidol (n = 1799). The risk difference was 0.4% (95% CI -0.9%-1.6%), the risk ratio was 1.25 (95% CI 0.59-2.65).


CONCLUSIONS
This meta-analysis of placebo-controlled randomized trials does not show that conventional antipsychotics in general or haloperidol in particular increase the risk of mortality in elderly patients. It questions the observational findings and the warning based on these findings.
University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen, The Netherlands; Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University, Amsterdam, The Netherlands.
Tessa A
TA
Hulshof
University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen, The Netherlands.
Sytse U
SU
Zuidema
Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
Raymond W J G
RW
Ostelo
University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen, The Netherlands; Department of Geriatric Psychiatry, BAVO Europoort, Rotterdam, The Netherlands. Electronic address: h.j.luijendijk@umcg.nl.
Hendrika J
HJ
Luijendijk
D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003693:Delirium / Q000188:drug therapy; D003704:Dementia / Q000188:drug therapy; D006801:Humans; D009026:Mortality; D016032:Randomized Controlled Trials as Topic
D014150:Antipsychotic Agents
Meta-analysis; conventional antipsychotics; dementia; elderly; mortality