Pharmacological treatments for alleviating agitation in dementia: A systematic review and network meta-analysis.

AIMS:

To determine the most efficacious and acceptable treatments of agitation in dementia.

METHODS:

MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched to 7 February 2017. Two independent reviewers selected randomised controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardised forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using multivariate random-effects meta-regressions. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for eight weeks.

RESULTS:

Thirty-six RCTs comprising 5,585 participants (30.9% male; mean [SD] age, 81.8 [4.9] years) were included. Dextromethorphan/quinidine (OR 3.04; 95% CI, 1.63-5.66), risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors (SSRIs) as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had non-inferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses.

CONCLUSIONS:

Risperidone, SSRIs as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.