The Effect of Side Effects on Antidepressant Efficacy : A Meta-Regression

Abstract

Antidepressants are the second most prescribed drug in the US. In Finland, it is estimated that over 400 000 people use antidepressants. Despite their widespread use, it has been noted that drug effects might be overestimated in efficacy RCTs. According to the interactive model, contextual and methodological factors in RCTs, such as internal sensations and the chance of receiving the drug, lead to an enhanced placebo effect in the drug group. Hence, we examined whether there is support for the interactive model by investigating whether there is a relationship between side effects and antidepressant efficacy. Two separate meta-regression analyses were conducted on a dataset comparing antidepressants to an inert (passive) placebo. The results of our primary analysis showed a significant positive relationship between a proxy for side effects and efficacy. Our secondary analysis revealed a significant negative relationship between the likelihood of receiving the drug and efficacy. Based on these findings, it was concluded that there is a relationship between side effects and efficacy. This supports the inference that the current efficacy paradigm overestimates both drug efficacy and drug effects. These findings are important for improving the design of efficacy trials in antidepressant research.