Clinician Article

Comparative efficacy of interventions for reducing symptoms of depression in people with dementia: systematic review and network meta-analysis.

  • Watt JA
  • Goodarzi Z
  • Veroniki AA
  • Nincic V
  • Khan PA
  • Ghassemi M, et al.
BMJ. 2021 Mar 24;372:n532. doi: 10.1136/bmj.n532. (Review)
PMID: 33762262
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  • Psychiatry
    Relevance - 7/7
    Newsworthiness - 5/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 6/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 6/7
  • Geriatrics
    Relevance - 6/7
    Newsworthiness - 6/7
  • FM/GP/Mental Health
    Relevance - 6/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 5/7


OBJECTIVE: To describe the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia who experience depression as a neuropsychiatric symptom of dementia or have a diagnosis of a major depressive disorder.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Medline, Embase, the Cochrane Library, CINAHL, PsycINFO, and grey literature between inception and 15 October 2020.

ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised trials comparing drug or non-drug interventions with usual care or any other intervention targeting symptoms of depression in people with dementia.

MAIN OUTCOME MEASURES: Pairs of reviewers screened studies, abstracted aggregate level data, and appraised risk of bias with the Cochrane risk of bias tool, which facilitated the derivation of standardised mean differences and back transformed mean differences (on the Cornell scale for depression in dementia) from bayesian random effects network meta-analyses and pairwise meta-analyses.

RESULTS: Of 22 138 citations screened, 256 studies (28 483 people with dementia) were included. Missing data posed the greatest risk to review findings. In the network meta-analysis of studies including people with dementia without a diagnosis of a major depressive disorder who were experiencing symptoms of depression (213 studies; 25 177 people with dementia; between study variance 0.23), seven interventions were associated with a greater reduction in symptoms of depression compared with usual care: cognitive stimulation (mean difference -2.93, 95% credible interval -4.35 to -1.52), cognitive stimulation combined with a cholinesterase inhibitor (-11.39, -18.38 to -3.93), massage and touch therapy (-9.03, -12.28 to -5.88), multidisciplinary care (-1.98, -3.80 to -0.16), occupational therapy (-2.59, -4.70 to -0.40), exercise combined with social interaction and cognitive stimulation (-12.37, -19.01 to -5.36), and reminiscence therapy (-2.30, -3.68 to -0.93). Except for massage and touch therapy, cognitive stimulation combined with a cholinesterase inhibitor, and cognitive stimulation combined with exercise and social interaction, which were more efficacious than some drug interventions, no statistically significant difference was found in the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia without a diagnosis of a major depressive disorder. Clinical and methodological heterogeneity precluded network meta-analysis of studies comparing the efficacy of interventions specifically for reducing symptoms of depression in people with dementia and a major depressive disorder (22 studies; 1829 patients).

CONCLUSIONS: In this systematic review, non-drug interventions were found to be more efficacious than drug interventions for reducing symptoms of depression in people with dementia without a major depressive disorder.


Clinical Comments

FM/GP/Mental Health

This finding should be disseminated widely in the hope of reducing unnecessary antidepressant medication that is frequently prescribed to elderly and demented patients instead of employing behavioural interventions with evidence of efficacy.


Helpful systematic review and meta-analysis showing non-drug approaches work better to improve depression symptoms in dementia than drug approaches.


Although there are limitations, these results are important to decrease drug prescription among people with dementia who are experiencing depressive symptoms.

Internal Medicine

I think most practitioners do not use anticholinesterases in dementia to prevent depression.

Internal Medicine

Dementia is a disabling diagnosis not just for patients but also for their family. Most patients are already on a myriad of medications or, at minimum, at an age where the initiation of new medications poses additional harm. Although the study provided validation that non-pharmacologic interventions can be as effective as pharmacotherapy, not all institutions will have access to many of the modalities discussed. Also, the extent of dementia may make it nearly impossible for families to utilize.


The critical issue here is the availability of non-pharmacologic interventions in a healthcare sector that often does not provide quality care.

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