Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Diseases, 2023, Brasanac et al

Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Diseases
An Umbrella Systematic Review and Meta-Analysis
JAMA Psychiatry: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2809163

Key Points

Question What is the evidence for use of antidepressants to treat or prevent comorbid depression in patients with medical diseases?

Findings This umbrella 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; results indicated sufficient quality of the individual meta-analyses but rather low quality of the meta-analyzed clinical trials. Compared with placebo, antidepressants showed better efficacy and worse tolerability and acceptability and were more likely to prevent depression.

Meaning Antidepressants are effective and safe for the treatment and prevention of depression in patients with medical diseases, but too few large, high-quality trials exist.


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.

 

Posting this because it seems to continue the usual problem in evidence-based medicine where conclusions are simply not supported by their own data.

This is a systematic review of systematic reviews, making a positive recommendation for SSRIs, despite acknowledging that there is no good evidence for it. But there is bad evidence for it, and that's how evidence-based medicine really works. It simply glosses over the major issues with side effects and withdrawal, which are not assessed in safety concerns and systematically minimized, even denied, and in many cases is a reason why patients keep on using them, while using discontinuation as the metric for acceptability. Which is as sensible as concluding that opiates are tolerated since users tend to keep using them.

There is recognition that they are tolerated worse than no treatment/placebo, while the evidence continues to be flimsy at best. But the conclusion remains that they are safe and effective. Somehow.

The introduction mentions a 5% prevalence of major depressive disorder, which is obviously incorrect. Rates of depression aren't just routinely, but even as a standard, overestimated because assessment questionnaires have many overlapping questions with unrelated health issues, especially so in patients with comorbid medical disease. Depression may be the most inflated diagnosis in all healthcare, it doesn't even have standardized criteria. Well, at least they are almost never followed.

SSRIs are one of the most commonly prescribed drug category, and yet evidence for their effectiveness remains very poor. This is especially concerning in populations suffering from chronic disease, as more often than not when the disease is adequately treated, the illusion of "depression", based on questionnaires with questions that overlap with illness, disappears. Medicine continues to stubbornly conflate illness with mood disorders, probably the most common mistake they've ever made.