| Key points |
What is the evidence for the use of antidepressants to treat or prevent comorbid depression in patients with medical illnesses? Findings This comprehensive systematic review identified 176 individual systematic reviews of randomized clinical trials in 43 medical diseases and quantitatively summarized and meta-analyzed the results of 52 meta-analyses of antidepressant effects in 27 medical diseases; The results indicated a sufficient quality of the individual meta-analyses but a rather low quality of the meta-analyzed clinical trials. Compared with placebo, antidepressants showed greater efficacy and worse tolerability and acceptability and were more likely to prevent depression. Which means that antidepressants are effective and safe for the treatment and prevention of depression in patients with medical illnesses, but there are very few large, high-quality trials. |
Major depressive disorder ( MDD) has a point prevalence of approximately 5% in the general population. Among people with medical illnesses, MDD represents one of the most common comorbidities, with a point prevalence often exceeding 10% or even 20%. Additionally, many more patients present with subclinical depressive symptoms. Treatment of depression comorbid with medical illnesses is important because depression in these populations is associated with lower quality of life and poorer prognosis.
Antidepressants represent a first-line treatment, and the most recent meta-analysis of randomized clinical trials (RCTs) shows small to medium effect sizes for specific antidepressants compared to placebo for MDD in general. However, meta-analyses of antidepressant efficacy are primarily based on RCTs that excluded people with medical illnesses, potentially limiting generalizability. Given that one in three to six patients with a medical illness is treated with antidepressants, it is important to establish efficacy and safety in these patient populations.
Trials that have examined antidepressant treatment for depression comorbid with a medical illness tend to be more heterogeneous than pivotal trials for regulatory purposes, ranging from small academic trials to larger consortia across a wide range of different medical illnesses in different settings. clinical or geographical. This situation results in a complex landscape of evidence for the treatment of comorbid depression that requires careful examination.
Currently, to our knowledge, there is no direct quantitative comparison of evidence between all individual pharmacological strategies in comorbid depression. Furthermore, the quality of the included meta-analyses and RCTs has not been assessed, which is an essential step before treatment recommendations can be made with confidence.
To address this gap, we conducted an overall systematic review of all available evidence on antidepressant use in depression comorbid with medical illnesses. We hypothesized that antidepressants would be significantly superior to placebo in the treatment of patients with depression and medical illnesses and would be reasonably acceptable, with potential differences between different medical illnesses.
| Importance |
One in three to six patients with medical illnesses receives antidepressants, but regulatory trials generally exclude comorbid medical illnesses. Meta-analyses of antidepressants have shown small to medium effect sizes, but generalizability to clinical settings is unclear, where medical comorbidity is highly prevalent.
| Aim |
To conduct an overall systematic review of meta-analytic evidence and meta-analysis of the efficacy and safety of antidepressant use in populations with medical illnesses and comorbid depression.
We searched PubMed and EMBASE from inception to March 31, 2023 for systematic reviews with or without meta-analysis of randomized clinical trials (RCTs) examining the efficacy and safety of antidepressants for the treatment or prevention of depression. comorbid in any medical illness.
| Study selection |
Meta-analysis of placebo- or active-controlled RCTs studying antidepressants for depression in people with medical illnesses.
| Data extraction and synthesis |
Data extraction and quality assessment using a measurement tool for the evaluation of multiple systematic reviews (AMSTAR-2 and AMSTAR-Content) were performed by pairs of independent reviewers following PRISMA guidelines. When multiple 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 results and measures |
Antidepressant efficacy was presented as standardized mean differences (SMD) and tolerability (discontinuation for adverse effects) and acceptability (discontinuation for all causes) were presented as risk ratios (RR).
| Results |
Of 6,587 references, 176 systematic reviews were identified in 43 medical diseases. In total, 52 meta-analyses across 27 medical diseases were included in the evidence synthesis (mean [SD] AMSTAR-2 quality score, 9.3 [3.1], with a possible maximum of 16; mean [SD] AMSTAR score -Content, 2.4 [1.9], with a maximum possible of 9).
Among medical conditions (23 meta-analyses), antidepressants improved depression versus placebo (SMD, 0.42 [95% CI, 0.30-0.54]; I 2 = 76.5%), with SMDs higher 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, 1.13-1.32]). 1.64]) compared to placebo.
Antidepressants produced 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 the placebo.
Antidepressants were more likely to prevent depression than placebo (seven meta-analyses; RR, 0.43 [95% CI, 0.33-0.53]).
| Conclusions and relevance |
Despite the paucity of large, well-conducted RCTs studying antidepressants for comorbid depression in medical illnesses, this comprehensive systematic review and meta-analysis demonstrates that antidepressants are effective and safe for comorbid depression in medical illnesses, with similar effect sizes. to those reported for antidepressants in MDD without medical comorbidity. Additionally, antidepressants may prevent the development of depression in some medical illnesses, but this finding must be weighed against possible adverse effects.
It is important to detect and manage comorbid depression in patients with medical illnesses, and clinicians should choose treatments based on patient preferences and the risk-benefit ratio of the antidepressant.
Future large, high-quality RCTs should include direct comparisons between antidepressants to expand knowledge about potential differences in efficacy and safety between antidepressants for depression comorbid with medical illnesses and allow for more specific treatment recommendations for different medical illnesses.
