Pharmacological treatment of neuropsychiatric symptoms of dementia: A systematic review and network meta‐analysis

Abstract

AbstractBackgroundNeuropsychiatric symptoms (NPS) of dementia are a common issue in dementia patients. It generally presents as three disparate symptom clusters—agitation, psychosis, and mood disorders which have different biological and psychosocial triggers. Therefore, a “one size fits all” solution may not exist. Pharmacological treatments are its treatment of choice, but there is controversy about which agent should be used. We aimed to update and expand our previous work to compare and rank drugs for the treatment of neuropsychiatric symptoms of dementia.MethodsWe included all randomized controlled trials reported as double‐blind and comparing one active drug with another or with placebo. Studies searched Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, from database inception to Jun 28, 2019. Our primary outcome was change in overall neuropsychiatric symptoms measured with standardised rating scales. And the secondary outcomes were change in aggressive behavior, psychosis, apathy, and depressive symptoms. Effect size measures were standardised mean differences (SMD) with 95% credible intervals (CrIs). We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking probabilities. We conducted subgroup analyses to assess the robustness of our findings. Confidence in the evidence was assessed using CINeMA. The study protocol is registered with PROSPERO, number CRD42019132231.ResultsWe identified 8175 citations and of these included 114 trials comprising nearly thirty thousand participants. Effect size estimates suggested galantamine was more effective than placebo for reducing overall neuropsychiatric symptoms. SMD compared with placebo for reduction of aggressive behavior found that aripiprazole and risperidone appeared to be more efficacious, citalopram and methylphenidate for reduction of apathy symptoms, memantine and donepezil for reduction of psychosis. While the certainty of evidence was low to very low.ConclusionThis systematic review synthesized the available evidence on the comparative efficacy of different pharmacological approaches in the management of overall NPS, agitation, psychosis, apathy and depressive symptoms in dementia patients. These results may serve evidence‐based practice and inform patients, physicians, guideline developers. Especially, clinicians should differentiate these disparate symptom clusters since the appreciation of such complexity is vital to determine the appropriate treatment.