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Findings Dispute Personalizing Antidepressant Treatment Based on Total Depression Scores

February 23, 2021

The widely held assumption that individual differences underlie the variability in the association between total depression scores and antidepressant treatment may not be valid, according to a meta-analysis recently published online in JAMA Psychiatry.

Researchers analyzed 91 double-blind, randomized placebo-controlled clinical trials studying the use of antidepressants in major depression. The mean age of the 18,965 participants was 44.18 years, and 62% were women.

The study found no evidence that variability in observed response among participants receiving antidepressants was greater than with those receiving a placebo. Variability was not associated with baseline depression severity or study year.

"Our findings do not provide empirical support for efforts to personalize antidepressant treatment based on total depression scores," researchers said.

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An earlier version of the study, published in JAMA Psychiatry on February 19, 2020, was retracted in June 2020.

“A vigorous methodologic debate has been taking place on the best way to assess the variability in response to psychiatric treatment,” researchers said. “Several previously published articles have relied on methods that make assumptions about the nature of the mean-SD relationship, which could lead to biased estimates if these assumptions are not met.”

To address that consideration, this study utilized a random-slope mixed-effects model to account for the association between end point depression scores and variability by modeling their relationship directly from the data.

In the updated analysis, the variability in response to noradrenergic agents was higher than to selective serotonin reuptake inhibitors, researchers found. Researchers suggest the difference may be because antidepressants primarily affecting norepinephrine may have a more significant effect on depressive symptoms than antidepressants that solely affect synaptic serotonin.

Researchers suggest that the next step towards optimizing treatments should include examining the evidence for variability in responses to antidepressants based on specific symptoms such as suicidality, symptom profiles, or sets of biomarkers. There may not be individual differences or biomarkers that capture the shared variance of all major depressive symptoms, so a focus on total depression scores may impede progress in personalizing treatments, they wrote.

—Meagan Thistle


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. 2021 February 17;[Epub ahead of print].

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