Dataset Information

Individual response to antidepressants for depression in adults-a meta-analysis and simulation study.

ABSTRACT: BACKGROUND:The observation that some patients appear to respond better to antidepressants for depression than others encourages the assumption that the effect of antidepressants differs between individuals and that treatment can be personalized. OBJECTIVE:To compare the outcome variance in patients receiving antidepressants with the outcome variance in patients receiving placebo in randomized controlled trials (RCTs) of adults with major depressive disorder (MDD) and to illustrate, using simulated data, components of variation of RCTs. METHODS:From a dataset comprising 522 RCTs of antidepressants for adult MDD, we selected the placebo-controlled RCTs reporting outcomes on the 17 or 21 item Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Rating Scale and extracted the means and SDs of raw endpoint scores or baseline to endpoint changes scores on eligible depression symptom rating scales. We conducted inverse variance random-effects meta-analysis with the variability ratio (VR), the ratio between the outcome variance in the group of patients receiving antidepressants and the outcome variance in the group receiving placebo, as the primary outcome. An increased variance in the antidepressant group would indicate individual differences in response to antidepressants. RESULTS:We analysed 222 RCTs that investigated 19 different antidepressants compared with placebo in 345 comparisons, comprising a total of 61144 adults with an MDD diagnosis. Across all comparisons, the VR for raw endpoint scores was 0.98 (95% CI 0.96 to 1.00, I2 = 0%) and 1.00 (95% CI 0.99 to 1.02, I2 = 0%) for baseline-to-endpoint change scores. CONCLUSION:Based on these data, we cannot reject the null hypothesis of equal variances in the antidepressant group and the placebo group. Given that RCTs cannot provide direct evidence for individual treatment effects, it may be most reasonable to assume that the average effect of antidepressants applies also to the individual patient.

SUBMITTER: Munkholm K

PROVIDER: S-EPMC7451660 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Individual response to antidepressants for depression in adults-a meta-analysis and simulation study.

Munkholm Klaus K Winkelbeiner Stephanie S Homan Philipp P Homan Philipp P

PloS one 20200827 8

<h4>Background</h4>The observation that some patients appear to respond better to antidepressants for depression than others encourages the assumption that the effect of antidepressants differs between individuals and that treatment can be personalized.<h4>Objective</h4>To compare the outcome variance in patients receiving antidepressants with the outcome variance in patients receiving placebo in randomized controlled trials (RCTs) of adults with major depressive disorder (MDD) and to illustrate ...[more]

PMID: 32853222

Similar Datasets

Project description:ImportanceAntidepressants are commonly used worldwide to treat major depressive disorder. Symptomatic response to antidepressants can vary depending on differences between individuals; however, this variability may reflect nonspecific or random factors.ObjectivesTo investigate the assumption of systematic variability in symptomatic response to antidepressants and to assess whether this variability is associated with severity of major depressive disorder, antidepressant class, or year of study publication.Data sourcesData used were from a recent network meta-analysis of acute treatment with licensed antidepressants in adults with major depressive disorder. The following databases were searched from inception to January 8, 2016: the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, and PsycINFO. Additional sources were international trial registries, drug approval agency websites, and key scientific journals.Study selectionAnalysis was restricted to double-blind, randomized placebo-controlled trials with available data at the study's end point.Data extraction and synthesisBaseline and end point means, SDs, number of participants in each group, antidepressant class, and publication year were extracted. The data were analyzed between August 14 and November 18, 2019.Main outcomes and measuresWith the use of validated methods, coefficients of variation were derived for antidepressants and placebo, and their ratios were calculated to compare outcome variability between antidepressant and placebo. Ratios were entered into a random-effects model, with the expectation that response to antidepressants would be more variable than response to placebo. Analysis was repeated after stratifying by baseline severity of depression, antidepressant class (selective serotonin reuptake inhibitors: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and vilazodone; serotonin and norepinephrine reuptake inhibitors: desvenlafaxine and venlafaxine; norepinephrine-dopamine reuptake inhibitor: bupropion; noradrenergic agents: amitriptyline and reboxetine; and other antidepressants: agomelatine, mirtazapine, and trazodone), and publication year.ResultsIn the 87 eligible randomized placebo-controlled trials (17 540 unique participants), there was significantly more variability in response to antidepressants than to placebo (coefficients of variation ratio, 1.14; 95% CI, 1.11-1.17; P < .001). Baseline severity of depression did not moderate variability in response to antidepressants. Variability in response to selective serotonin reuptake inhibitors was lower than variability in response to noradrenergic agents (coefficients of variation ratio, 0.88; 95% CI, 0.80-0.97; P = .01), as was the variability in response to other antidepressants compared with noradrenergic agents (coefficients of variation ratio, 0.87; 95% CI, 0.79-0.97; P = .001). Variability also tended to be lower in studies that were published more recently, with coefficients of variation changing by a value of 0.005 (95% CI, 0.002-0.008; P = .003) for every year a study is more recent.Conclusions and relevanceIndividual differences may be systematically associated with responses to antidepressants in major depressive disorder beyond placebo effects or statistical factors. This study provides empirical support for identifying moderators and personalizing antidepressant treatment.

Project description:ImportanceDepression frequently recurs. To prevent relapse, antidepressant medication is often taken in the long term. Sequentially delivering a psychological intervention while undergoing tapering of antidepressant medication might be an alternative to long-term antidepressant use. However, evidence is lacking on which patients may benefit from tapering antidepressant medication while receiving a psychological intervention and which should continue the antidepressant therapy. A meta-analysis of individual patient data with more power and precision than individual randomized clinical trials or a standard meta-analysis is warranted.ObjectivesTo compare the associations between use of a psychological intervention during and/or after antidepressant tapering vs antidepressant use alone on the risk of relapse of depression and estimate associations of individual clinical factors with relapse.Data sourcesPubMed, the Cochrane Library, Embase, and PsycInfo were last searched on January 23, 2021. Requests for individual participant data from included randomized clinical trials (RCTs) were sent.Study selectionRandomized clinical trials that compared use of a psychological intervention while tapering antidepressant medication with antidepressant monotherapy were included. Patients had to be in full or partial remission from depression. Two independent assessors conducted screening and study selection.Data extraction and synthesisOf 15 792 screened studies, 236 full-text articles were retrieved, and 4 RCTs that provided individual participant data were included.Main outcomes and measuresTime to relapse and relapse status over 15 months measured via a blinded assessor using a diagnostic clinical interview.ResultsIndividual data from 714 participants (mean [SD] age, 49.2 [11.5] years; 522 [73.1%] female) from 4 RCTs that compared preventive cognitive therapy or mindfulness-based cognitive therapy during and/or after antidepressant tapering vs antidepressant monotherapy were available. Two-stage random-effects meta-analysis found no significant difference in time to depressive relapse between use of a psychological intervention during tapering of antidepressant medication vs antidepressant therapy alone (hazard ratio [HR], 0.86; 95% CI, 0.60-1.23). Younger age at onset (HR, 0.98; 95% CI, 0.97-0.99), shorter duration of remission (HR, 0.99; 95% CI, 0.98-1.00), and higher levels of residual depressive symptoms at baseline (HR, 1.07; 95% CI, 1.04-1.10) were associated with a higher overall risk of relapse. None of the included moderators were associated with risk of relapse.Conclusions and relevanceThe findings of this individual participant data meta-analysis suggest that regardless of the clinical factors included in these studies, the sequential delivery of a psychological intervention during and/or after tapering may be an effective relapse prevention strategy instead of long-term use of antidepressants. These results could be used to inform shared decision-making in clinical practice.

Dataset Information

Individual response to antidepressants for depression in adults-a meta-analysis and simulation study.

Publications

Individual response to antidepressants for depression in adults-a meta-analysis and simulation study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets