Antipsychotic medications for the treatment of delirium: A systematic review and meta-analysis of randomised controlled trials

Objectives We performed an updated meta-analysis of antipsychotic treatment in patients with delirium, based on a previous meta-analysis published in 2007. Methods Included in this study were randomised, placebo-controlled or usual care (UC) controlled trials of antipsychotics in adult patients with delirium. Our primary outcome measure was response rate at the study end point. The secondary outcome measures included improvement of severity of delirium, Clinical Global Impression-Severity Scale (CGI-S), time to response (TTR), discontinuation rate and individual adverse effects. The risk ratio (RR), the number-needed-to-treat/harm (NNT/ NNH), 95% CIs and standardised mean difference (SMD), were calculated. Results We identified 15 studies (mean duration: 9.8 days) for the systematic review (total n=949, amisulpride=20, aripiprazole=8, chlorpromazine=13, haloperidol=316, intramuscular olanzapine or haloperidol injection=62, olanzapine=144, placebo=75, quetiapine=125, risperidone=124, UC=30 and ziprasidone=32), 4 of which were conference abstracts and unpublished. When pooled as a group, antipsychotics were superior to placebo/UC in terms of response rate (RR=0.22, NNT=2), delirium severity scales scores (SMD=-1.27), CGI-S scores (SMD=-1.57) and TTR (SMD=-1.22). The pooled antipsychotic group was associated with a higher incidence of dry mouth (RR=13.0, NNH=5) and sedation (RR=4.59, NNH=5) compared with placebo/UC. Pooled second-generation antipsychotics (SGAs) were associated with shorter TTR (SMD=-0.27) and a lower incidence of extrapyramidal symptoms (RR=0.31, NNH=7) compared with haloperidol. Conclusions Our results suggested that SGAs have a benefit for the treatment of delirium with regard to efficacy and safety compared with haloperidol. However, further study using larger samples is required.