Where do the individual differences in depression treatment come from?

 It is often said that the individual variability of patients with depression (major depressive disorder, MDD) in response to medications is great.

Recently, a meta-analysis study tried to use the latest statistical methods to analyze this statement-unlike some previous meta-analysis, the researchers did not assume the connection between the mean and the variance, they used the random slope mixed effects model ( random-slope mixed-effects model) can directly use data to estimate this relationship. The primary question discussed in the study is: in randomised control trials (RCT), whether the individual difference in symptom improvement of patients who received antidepressant (AD) treatment will be greater than that of the placebo group What about? It should be noted that due to the limitation of data sources, the study only focused on the changes in the total scores of patients on the depression scale, and did not pay attention to the potential differences in specific symptoms or biomarkers.

The results showed that although the difference in response of the drug treatment group was about 2% more than that of the placebo group as a whole, the difference was not significant. Looking at the different types of drugs alone, the researchers did not find a significant difference. At the same time, researchers are also concerned that some antidepressants will act on multiple neurotransmitter systems at the same time. Are the individual response differences brought about by these drugs greater than some more specific drugs? Pairwise comparison shows that only the comparison between noradrenaline (NA) and Selective Serontonin Reuptake Inhibitors (SSRI) has a significant difference, but this may be different from NA The longer the course of the drug is related to the length of the treatment. In addition, there was no significant effect on the baseline severity of depression before treatment and the experimental year.

How to interpret these results? The researchers said that the so-called Heterogeneity of treatment effect (HTE) is not reflected in the total score of the depression scale, because the "efficacy" of the placebo group is also variable. However, it is worth noting that there was also a review published in the same journal, whose author believes that the existing meta-analysis methods cannot estimate the covariance between the placebo effect and the drug efficacy. If the covariance is less than zero, it can offset the difference in variance between the two groups. Therefore, the non-significant results obtained by the study are difficult to completely rule out the existence of HTE. The consensus of the two articles is that future attempts at individualized medicine should focus on specific symptoms and biomarkers, while HTE research should also focus on individual differences in non-drug treatments.

References: Maslej MM, Furukawa TA, Cipriani A, Andrews PW, Mulsant BH. Individual Differences in Response to Antidepressants: A Meta-analysis of Placebo-Controlled Randomized Clinical Trials. JAMA Psychiatry. 2020;77(6):607–617.

DOI: https://doi.org/10.1001/jamapsychiatry.2020.4564