Pharmacotherapy of Behavioral and Psychological Symptoms of Dementia: State of the Art and Future Progress

Introduction: Nonpharmacological therapies (NPTs) can improve the quality of life (QoL) of people with Alzheimer’s disease (AD) and their carers. The objective of this study was to evaluate the best evidence on the effects of NPTs in AD and related disorders (ADRD) by performing a systematic review and meta-analysis of the entire field. Methods: Existing reviews and major electronic databases were searched for randomized controlled trials (RCTs). The deadline for study inclusion was September 15, 2008. Intervention categories and outcome domains were predefined by consensus. Two researchers working together detected 1,313 candidate studies of which 179 RCTs belonging to 26 intervention categories were selected. Cognitive deterioration had to be documented in all participants, and degenerative etiology (indicating dementia) had to be present or presumed in at least 80% of the subjects. Evidence tables, meta-analysis and summaries of results were elaborated by the first author and reviewed by author subgroups. Methods for rating level of evidence and grading practice recommendations were adapted from the Oxford Center for Evidence-Based Medicine. Results: Grade A treatment recommendation was achieved for institutionalization delay (multicomponent interventions for the caregiver, CG). Grade B recommendation was reached for the person with dementia (PWD) for: improvement in cognition (cognitive training, cognitive stimulation, multicomponent interventions for the PWD); activities of daily living (ADL) (ADL training, multicomponent interventions for the PWD); behavior (cognitive stimulation, multicomponent interventions for the PWD, behavioral interventions, professional CG training); mood (multicomponent interventions for the PWD); QoL (multicomponent interventions for PWD and CG) and restraint prevention (professional CG training); for the CG, grade B was also reached for: CG mood (CG education, CG support, multicomponent interventions for the CG); CG psychological well-being (cognitive stimulation, multicomponent interventions for the CG); CG QoL (multicomponent interventions for PWD and CG). Conclusion: NPTs emerge as a useful, versatile and potentially cost-effective approach to improve outcomes and QoL in ADRD for both the PWD and CG.

This systematic overview reports findings from systematic reviews of randomized controlled trials of pharmacological and non-pharmacological interventions for behavioural and psychological symptoms of dementia (BPSD). The Cochrane Database of Systematic Reviews, DARE, Medline, EMBASE, and PsycINFO were searched to September 2015. Fifteen systematic reviews of eighteen different interventions were included. A significant improvement in BPSD was seen with: functional analysis-based interventions (GRADE quality of evidence moderate; standardized mean difference (SMD) −0.10, 95%CI −0.20 to 0.00), music therapy (low; SMD −0.49, 95%CI −0.82 to −0.17), analgesics (low; SMD −0.24, 95%CI −0.47 to −0.01), donepezil (high; SMD −0.15 95% CI −0.29 to −0.01), galantamine (high; SMD −0.15, 95%CI −0.28 to −0.03), and antipsychotics (high; SMD −0.13, 95%CI −0.21 to −0.06). The estimate of effect size for most interventions was small. Although some pharmacological interventions had a slightly larger effect size, current evidence suggests functional analysis-based interventions should be used as first line management of BPSD whenever possible due to the lack of associated adverse events. Music therapy may also be beneficial, but further research is required as the quality of evidence to support its use is low. Cholinesterase inhibitors donepezil and galantamine should be trialled for the management of BPSD where non-pharmacological treatments have failed. Low-quality evidence suggests that assessment of pain should be conducted and a stepped analgesic approach trialled when appropriate. Antipsychotics have proven effectiveness but should be avoided where possible due to the high risk of serious adverse events and availability of safer alternatives.