Is there evidence that response to antidepressants varies based on individual differences?
In this meta-analysis of 91 randomized clinical trials (18 965 participants) on the use of antidepressants in major depression, no evidence was found of more variability in response to antidepressants than to placebo. Variability was not associated with baseline depression severity or study year, but variability in response to noradrenergic agents was higher than that of selective serotonin reuptake inhibitors.
Individual differences may not underlie variability in the association between total depression scores and antidepressant treatment; future efforts toward personalization should focus on individual symptoms or biomarkers.
Antidepressants are commonly used to treat major depressive disorder (MDD). Antidepressant outcomes can vary based on individual differences; however, it is unclear whether specific factors determine this variability or whether it is at random.
To investigate the assumption of systematic variability in symptomatic response to antidepressants and to assess whether variability is associated with MDD severity, antidepressant class, or study publication year.
Data used were updated from a network meta-analysis of treatment with licensed antidepressants in adults with MDD. The Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, and PsycInfo were searched from inception to March 21, 2019. Additional sources were international trial registries and sponsors, drug companies and regulatory agencies’ websites, and reference lists of published articles. Data were analyzed between June 8, 2020, and June 13, 2020.
Analysis was restricted to double-blind, randomized placebo-controlled trials with depression scores available at the study’s end point.
Data Extraction and Synthesis
Baseline means, number of participants, end point means and SDs of total depression scores, antidepressant type, and publication year were extracted.
Main Outcomes and Measures
Log SDs (bln σ̂) were derived for treatment groups (ie, antidepressant and placebo). A random-slope mixed-effects model was conducted to estimate the difference in bln σ̂ between treatment groups while controlling for end point mean. Secondary models determined whether differences in variability between groups were associated with baseline MDD severity; antidepressant class (selective serotonin reuptake inhibitors and other related drugs; serotonin and norepinephrine reuptake inhibitors; norepinephrine-dopamine reuptake inhibitors; noradrenergic agents; or other antidepressants); and publication year.
In the 91 eligible trials (18 965 participants), variability in response did not differ significantly between antidepressants and placebo (bln σ̂, 1.02; 95% CI, 0.99-1.05; P = .19). This finding is consistent with a range of treatment effect SDs (up to 16.10), depending on the association between the antidepressant and placebo effects. Variability was not associated with baseline MDD severity or publication year. Responses to noradrenergic agents were 11% more variable than responses to selective serotonin reuptake inhibitors (bln σ̂, 1.11; 95% CI, 1.01-1.21; P = .02).
Conclusions and Relevance
Although this study cannot rule out the possibility of treatment effect heterogeneity, it does not provide empirical support for personalizing antidepressant treatment based solely on total depression scores. Future studies should explore whether individual symptom scores or biomarkers are associated with variability in response to antidepressants.
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Maslej MM, Furukawa TA, Cipriani A, et al. Individual Differences in Response to Antidepressants: A Meta-analysis of Placebo-Controlled Randomized Clinical Trials. JAMA Psychiatry. Published online February 17, 2021. doi:10.1001/jamapsychiatry.2020.4564
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