Dataset Information

Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Diseases: An Umbrella Systematic Review and Meta-Analysis.

ABSTRACT:

Importance

Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of antidepressants have shown small to medium effect sizes, but generalizability to clinical settings is unclear, where medical comorbidity is highly prevalent.

Objective

To perform an umbrella systematic review of the meta-analytic evidence and meta-analysis of the efficacy and safety of antidepressant use in populations with medical diseases and comorbid depression.

Data sources

PubMed and EMBASE were searched from inception until March 31, 2023, for systematic reviews with or without meta-analyses of randomized clinical trials (RCTs) examining the efficacy and safety of antidepressants for treatment or prevention of comorbid depression in any medical disease.

Study selection

Meta-analyses of placebo- or active-controlled RCTs studying antidepressants for depression in individuals with medical diseases.

Data extraction and synthesis

Data extraction and quality assessment using A Measurement Tool for the Assessment of Multiple Systematic Reviews (AMSTAR-2 and AMSTAR-Content) were performed by pairs of independent reviewers following PRISMA guidelines. When several meta-analyses studied the same medical disease, the largest meta-analysis was included. Random-effects meta-analyses pooled data on the primary outcome (efficacy), key secondary outcomes (acceptability and tolerability), and additional secondary outcomes (response and remission).

Main outcomes and measures

Antidepressant efficacy presented as standardized mean differences (SMDs) and tolerability (discontinuation for adverse effects) and acceptability (all-cause discontinuation) presented as risk ratios (RRs).

Results

Of 6587 references, 176 systematic reviews were identified in 43 medical diseases. Altogether, 52 meta-analyses in 27 medical diseases were included in the evidence synthesis (mean [SD] AMSTAR-2 quality score, 9.3 [3.1], with a maximum possible of 16; mean [SD] AMSTAR-Content score, 2.4 [1.9], with a maximum possible of 9). Across medical diseases (23 meta-analyses), antidepressants improved depression vs placebo (SMD, 0.42 [95% CI, 0.30-0.54]; I2 = 76.5%), with the largest SMDs for myocardial infarction (SMD, 1.38 [95% CI, 0.82-1.93]), functional chest pain (SMD, 0.87 [95% CI, 0.08-1.67]), and coronary artery disease (SMD, 0.83 [95% CI, 0.32-1.33]) and the smallest for low back pain (SMD, 0.06 [95% CI, 0.17-0.39]) and traumatic brain injury (SMD, 0.08 [95% CI, -0.28 to 0.45]). Antidepressants showed worse acceptability (24 meta-analyses; RR, 1.17 [95% CI, 1.02-1.32]) and tolerability (18 meta-analyses; RR, 1.39 [95% CI, 1.13-1.64]) compared with placebo. Antidepressants led to higher rates of response (8 meta-analyses; RR, 1.54 [95% CI, 1.14-1.94]) and remission (6 meta-analyses; RR, 1.43 [95% CI, 1.25-1.61]) than placebo. Antidepressants more likely prevented depression than placebo (7 meta-analyses; RR, 0.43 [95% CI, 0.33-0.53]).

Conclusions and relevance

The results of this umbrella systematic review of meta-analyses found that antidepressants are effective and safe in treating and preventing depression in patients with comorbid medical disease. However, few large, high-quality RCTs exist in most medical diseases.

SUBMITTER: Kohler-Forsberg O

PROVIDER: S-EPMC10483387 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Diseases: An Umbrella Systematic Review and Meta-Analysis.

Köhler-Forsberg Ole O Stiglbauer Victoria V Brasanac Jelena J Chae Woo Ri WR Wagener Frederike F Zimbalski Kim K Jefsen Oskar H OH Liu Shuyan S Seals Malik R MR Gamradt Stefanie S Correll Christoph U CU Gold Stefan M SM Otte Christian C

JAMA psychiatry 20231201 12

<h4>Importance</h4>Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of antidepressants have shown small to medium effect sizes, but generalizability to clinical settings is unclear, where medical comorbidity is highly prevalent.<h4>Objective</h4>To perform an umbrella systematic review of the meta-analytic evidence and meta-analysis of the efficacy and safety of antidepressant use in popu ...[more]

PMID: 37672261

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Project description:BackgroundAntidepressant medicines are used to manage symptoms of low back pain. The efficacy, acceptability, and safety of antidepressant medicines for low back pain (LBP) are not clear. We aimed to evaluate the efficacy, acceptability, and safety of antidepressant medicines for LBP.MethodsWe searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov , the EU Clinical Trials Register, and the WHO International Clinical Trial Registry Platform from inception to May 2020. We included published and trial registry reports of RCTs that allocated adult participants with LBP to receive an antidepressant medicine or a placebo medicine. Pairs of authors independently extracted data in duplicate. We extracted participant characteristics, study sample size, outcome values, and measures of variance for each outcome. We data using random-effects meta-analysis models and calculated estimates of effects and heterogeneity for each outcome. We formed judgments of confidence in the evidence in accordance with GRADE. We report our findings in accordance with the PRISMA statement. We prespecified all outcomes in a prospectively registered protocol. The primary outcomes were pain intensity and acceptability. We measured pain intensity at end-of-treatment on a 0-100 point scale and considered 10 points the minimal clinically important difference. We defined acceptability as the odds of stopping treatment for any reason.ResultsWe included 23 RCTs in this review. Data were available for pain in 17 trials and acceptability in 14 trials. Treatment with antidepressants decreased pain intensity by 4.33 points (95% CI - 6.15 to - 2.50) on a 0-100 scale, compared to placebo. Treatment with antidepressants increased the odds of stopping treatment for any reason (OR 1.27 [95% CI 1.03 to 1.56]), compared to placebo.ConclusionsTreatment of LBP with antidepressants is associated with small reductions in pain intensity and increased odds of stopping treatment for any reason, compared to placebo. The effect on pain is not clinically important. The effect on acceptability warrants consideration. These findings provide Level I evidence to guide clinicians in their use of antidepressants to treat LBP.Trial registrationWe prospectively registered the protocol for this systematic review on PROSPERO ( CRD42020149275 ).

Project description:ObjectiveTo investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to 15 November and updated on 12 May 2020.Eligibility criteria for study selectionRandomised controlled trials comparing the efficacy or safety, or both of any antidepressant drug with placebo (active or inert) in participants with low back or neck pain, sciatica, or hip or knee osteoarthritis.Data extraction and synthesisTwo independent reviewers extracted data. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). A random effects model was used to calculate weighted mean differences and 95% confidence intervals. Safety (any adverse event, serious adverse events, and proportion of participants who withdrew from trials owing to adverse events) was a secondary outcome. Risk of bias was assessed with the Cochrane Collaboration's tool and certainty of evidence with the grading of recommendations assessment, development and evaluation (GRADE) framework.Results33 trials (5318 participants) were included. Moderate certainty evidence showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference -5.30, 95% confidence interval -7.31 to -3.30) at 3-13 weeks and low certainty evidence that SNRIs reduced osteoarthritis pain (-9.72, -12.75 to -6.69) at 3-13 weeks. Very low certainty evidence showed that SNRIs reduced sciatica at two weeks or less (-18.60, -31.87 to -5.33) but not at 3-13 weeks (-17.50, -42.90 to 7.89). Low to very low certainty evidence showed that tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less (-7.55, -18.25 to 3.15) but did at 3-13 weeks (-15.95, -31.52 to -0.39) and 3-12 months (-27.0, -36.11 to -17.89). Moderate certainty evidence showed that SNRIs reduced disability from back pain at 3-13 weeks (-3.55, -5.22 to -1.88) and disability due to osteoarthritis at two weeks or less (-5.10, -7.31 to -2.89), with low certainty evidence at 3-13 weeks (-6.07, -8.13 to -4.02). TCAs and other antidepressants did not reduce pain or disability from back pain.ConclusionModerate certainty evidence shows that the effect of SNRIs on pain and disability scores is small and not clinically important for back pain, but a clinically important effect cannot be excluded for osteoarthritis. TCAs and SNRIs might be effective for sciatica, but the certainty of evidence ranged from low to very low.Systematic review registrationPROSPERO CRD42020158521.

Project description:ObjectiveTo provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain according to condition.DesignOverview of systematic reviews.Data sourcesPubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to 20 June 2022.Eligibility criteria for selecting studiesSystematic reviews comparing any antidepressant with placebo for any pain condition in adults.Data extraction and synthesisTwo reviewers independently extracted data. The main outcome measure was pain; for headache disorders it was frequency of headaches. Continuous pain outcomes were converted into a scale of 0 (no pain) to 100 (worst pain) and were presented as mean differences (95% confidence intervals). Dichotomous outcomes were presented as risk ratios (95% confidence intervals). Data were extracted from the time point closest to the end of treatment. When end of treatment was too variable across trials in a review, data were extracted from the outcome or time point with the largest number of trials and participants. Secondary outcomes were safety and tolerability (withdrawals because of adverse events). Findings were classified from each comparison as efficacious, not efficacious, or inconclusive. Certainty of evidence was assessed with the grading of recommendations assessment, development, and evaluation framework.Results26 reviews (156 unique trials and >25 000 participants) were included. These reviews reported on the efficacy of eight antidepressant classes covering 22 pain conditions (42 distinct comparisons). No review provided high certainty evidence on the efficacy of antidepressants for pain for any condition. 11 comparisons (nine conditions) were found where antidepressants were efficacious, four with moderate certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain (mean difference -5.3, 95% confidence interval -7.3 to -3.3), postoperative pain (-7.3, -12.9 to -1.7), neuropathic pain (-6.8, -8.7 to -4.8), and fibromyalgia (risk ratio 1.4, 95% confidence interval 1.3 to 1.6). For the other 31 comparisons, antidepressants were either not efficacious (five comparisons) or the evidence was inconclusive (26 comparisons).ConclusionsEvidence of efficacy of antidepressants was found in 11 of the 42 comparisons included in this overview of systematic reviews-seven of the 11 comparisons investigated the efficacy of SNRIs. For the other 31 comparisons, antidepressants were either inefficacious or evidence on efficacy was inconclusive. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain conditions.Systematic review registrationPROSPERO CRD42022311073.

Dataset Information

Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Diseases: An Umbrella Systematic Review and Meta-Analysis.

Importance

Objective

Data sources

Study selection

Data extraction and synthesis

Main outcomes and measures

Results

Conclusions and relevance

Publications

Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Diseases: An Umbrella Systematic Review and Meta-Analysis.

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