Individual Differences Linked to Antidepressant Response

Marta M. Maslej, PhD

While antidepressants are almost always prescribed for major depressive disorder, each individual responds differently to the different classes of drugs.

An investigative team, led by Marta M. Maslej, PhD, Department of Psychiatry at the University of Toronto, examined whether the response to antidepressants varies systemically based on the individual patient’s differences and whether variability is linked to the severity of major depressive disorder, antidepressant class, or how recent a study was conducted.

In the meta-analysis, the investigators examined 87 randomized clinical trials involving 17,540 unique participants on the use of antidepressants in individuals with major depression. Data was only complied from double-blind, randomized placebo-controlled trials with available data at the study’s end point.

The investigators derived coefficients of variation for antidepressants and placebos and calculated their ratios to compare outcome variability between treatment and placebos.

Ratios were entered into a random-effects model, with the expectation that the response to antidepressants would be more variable than response to placebo.

The team also repeated the analysis after stratifying by baseline severity of depression, publication year, and antidepressant class.

The investigators found there was 14% more variability in the response to antidepressants in treatment groups than in placebo controlled groups (coefficients of variation ratio, 1.14; 95% CI, 1.11-1.17; P&thinsp;<&thinsp;.001).

They also found that baseline severity of depression did not moderate the variability.

Ultimately, variability in response to selective serotonin reuptake inhibitors was lower than the variability in response to noradrenergic agents ((coefficients of variation ratio, 1.14; 95% CI, 1.11-1.17; P&thinsp;<&thinsp;.001).

This was also true for the variability in response to other antidepressants compared with noradrenergic agents (coefficients of variation ratio, 0.87; 95% CI, 0.79-0.97; P&thinsp;=&thinsp;.001).

Variability also was generally lower in more recent studies, with coefficients of variation changing by a value of 0.005 (95% CI, 0.002-0.008; P&thinsp;=&thinsp;.003) for every year a study is more recent.

“Individual differences may be systematically associated with responses to antidepressants in major depressive disorder beyond placebo effects or statistical factors,” the authors wrote. “This study provides empirical support for identifying moderators and personalizing antidepressant treatment.”

While antidepressants are often used to treat major depressive disorder, symptomatic responses can vary based on the differences between individuals and the efficacies of the individual drugs vary. However, it is unclear whether this reflects nonspecific or random factors.

The substantial variation observed in response to psychiatric medications has prompted efforts to identify moderators of treatment response and to personalize treatments to match antidepressants with the unique characteristics of individual patients.

Recently, investigators suggested random factors account for the observed variability in response to antipsychotics medications as well.

The investigators hypothesized that if responses to antipsychotics included systematic individual differences in addition to other factors such as placebo effects or statistical factors, then responders should be more variable than responses to placebo.

Placebos produced slightly more variable outcomes, which calls into question a widely held assumption that variability in response to antipsychotics could be due to individuals’ differences.

The study, “Individual Differences in Response to Antidepressants A Meta-analysis of Placebo-Controlled Randomized Clinical Trials,” was published online in JAMA Psychiatry.