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Dudas R, Malouf R, McCleery J, et al. Antidepressants for treating depression in dementia. Cochrane Database Syst Rev. 2018 Aug 31;8:CD003944. doi: 10.1002/14651858.CD003944.pub2.
Area Score
Psychiatry
FM/GP/Mental Health
Geriatrics
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Abstract

BACKGROUND: The use of antidepressants in dementia accompanied by depressive symptoms is widespread, but their clinical efficacy is uncertain. This review updates an earlier version, first published in 2002.

OBJECTIVES: To determine the efficacy and safety of any type of antidepressant for patients who have been diagnosed as having dementia of any type and depression as defined by recognised criteria.

SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, on 16 August 2017. ALOIS contains information on trials retrieved from databases and from a number of trial registers and grey literature sources.

SELECTION CRITERIA: We included all relevant double-blind, randomised trials comparing any antidepressant drug with placebo, for patients diagnosed as having dementia and depression.

DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion and extracted data independently. We assessed risk of bias in the included studies using the Cochrane 'Risk of bias' tool. Where clinically appropriate, we pooled data for treatment periods up to three months and from three to nine months. We used GRADE methods to assess the overall quality of the evidence.

MAIN RESULTS: We included ten studies with a total of 1592 patients. Eight included studies reported sufficiently detailed results to enter into analyses related to antidepressant efficacy. We split one study which included two different antidepressants and therefore had nine groups of patients treated with antidepressants compared with nine groups receiving placebo treatment. Information needed to make 'Risk of bias' judgements was often missing.We found high-quality evidence of little or no difference in scores on depression symptom rating scales between the antidepressant and placebo treated groups after 6 to 13 weeks (standardised mean difference (SMD) -0.10, 95% confidence interval (CI) -0.26 to 0.06; 614 participants; 8 studies). There was probably also little or no difference between groups after six to nine months (mean difference (MD) 0.59 point, 95% CI -1.12 to 2.3, 357 participants; 2 studies; moderate-quality evidence). The evidence on response rates at 12 weeks was of low quality, and imprecision in the result meant we were uncertain of any effect of antidepressants (antidepressant: 49.1%, placebo: 37.7%; odds ratio (OR) 1.71, 95% CI 0.80 to 3.67; 116 participants; 3 studies). However, the remission rate was probably higher in the antidepressant group than the placebo group (antidepressant: 40%, placebo: 21.7%; OR 2.57, 95% CI 1.44 to 4.59; 240 participants; 4 studies; moderate-quality evidence). The largest of these studies continued for another 12 weeks, but because of imprecision of the result we could not be sure of any effect of antidepressants on remission rates after 24 weeks. There was evidence of no effect of antidepressants on performance of activities of daily living at weeks 6 to 13 (SMD -0.05, 95% CI -0.36 to 0.25; 173 participants; 4 studies; high-quality evidence) and probably also little or no effect on cognition (MD 0.33 point on the Mini-Mental State Examination, 95% CI -1.31 to 1.96; 194 participants; 6 studies; moderate-quality evidence).Participants on antidepressants were probably more likely to drop out of treatment than those on placebo over 6 to 13 weeks (OR 1.51, 95% CI 1.07 to 2.14; 836 participants; 9 studies). The meta-analysis of the number of participants suffering at least one adverse event showed a significant difference in favour of placebo (antidepressant: 49.2%, placebo: 38.4%; OR 1.55, 95% CI 1.21 to 1.98, 1073 participants; 3 studies), as did the analyses for participants suffering one event of dry mouth (antidepressant: 19.6%, placebo: 13.3%; OR 1.80, 95% CI 1.23 to 2.63, 1044 participants; 5 studies), and one event of dizziness (antidepressant: 19.2%, placebo: 12.5%; OR 2.00, 95% CI 1.34 to 2.98, 1044 participants; 5 studies). Heterogeneity in the way adverse events were reported in studies presented a major difficulty for meta-analysis, but there was some evidence that antidepressant treatment causes more adverse effects than placebo treatment does.

AUTHORS' CONCLUSIONS: The available evidence is of variable quality and does not provide strong support for the efficacy of antidepressants for treating depression in dementia, especially beyond 12 weeks. On the only measure of efficacy for which we had high-quality evidence (depression rating scale scores), antidepressants showed little or no effect. The evidence on remission rates favoured antidepressants but was of moderate quality, so future research may find a different result. There was insufficient evidence to draw conclusions about individual antidepressant drugs or about subtypes of dementia or depression. There is some evidence that antidepressant treatment may cause adverse events.

Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

I did not know whether this review was newsworthy or not because I was confused by the authors' conclusion regarding the quality of the original studies reviewed and thus the quality of the synthesized evidence based on the studies selected. Specifically, the authors were "certain" that the quality of the primary outcome (reducing depressive symptoms as quantified by scales) was high yet the table (Fig. 2) showing the assessment for risk of bias in each original article did not support this statement. I was also concerned about how the individual studies were weighted in the meta-analysis. For example, in Fig. 5 the weight of the only study evaluating venlafaxine was unexpectedly high relative to the subgroup of SSRI when considering the total number of participants or the total number of events.

Geriatrics rater

This is a very difficult issue to clear up given the complexity of diagnosing depression in demented patients. Prevalence rates vary almost in any value due to lack of a reliable anamnesis or a good diagnostic tool, but it is worth the effort because there are so many patients with dementia taking antidepressants. According to this updated Cochrane meta-analysis, we have to bear in mind to avoiding adverse drug effects rather than expecting improvements with antidepressants.

Geriatrics rater

These interesting results seem to highlight the need for a definitive trial.

Psychiatry rater

Depression in dementia is very common; it's difficult to diagnose and difficult to treat. In this Cochrane meta analysis, the authors find that scores on depression scales do NOT go down in patients with antidepressant treatment. This seems to be a solid finding. However, just to confuse us, there is SOME evidence that patients with depression MIGHT respond to antidepressants. Patients treated with antidepressants might have more side effects. Clinicians will not be surprised but will be puzzled by this.