Societal well-being is reflected in outcomes of antidepressant clinical trials.

Abstract

Abstract Objective Placebo effect has been found to be a significant contributor to the outcomes of antidepressant treatment, leading to questions about its overall efficacy. Previous research has shown that global societal trends and events such as economic recessions and pandemics, significantly affect people's mental health. The relationship between the two has not previously been examined. The present study investigated how global social sentiment, as indexed by global suicide rates, is related to the the treatment response in clinical trials of antidepressants. Methods We scrutinized data from a 1979–2016 meta-analysis of antidepressant clinical trials for depression. Outcomes from placebo and active groups, including responders, remitters, and dropouts, were matched with annual global suicide rates. Linear and non-linear methods were leveraged to estimate effect-sizes. Results During periods with high suicide rates, placebo groups displayed fewer responders (r=-0.38,P < 0.001) and remitters (r=-0.42,P < 0.001), and a higher dropout rate (r = 0.56,P < 0.001). Active groups exhibited a similar pattern, but the placebo arms were affected more strongly. The findings held true after applying non-linear methods, alternative metrics, and accounting for initial depression severity, group size, publication year, trial duration, proportion of multi-center studies. Specificity analyses revealed that earlier suicide rates had stronger association with the trial outcomes, and in a subsample of studies conducted in North America suicide rates from more culturally distant countries had weaker association with the outcomes. Conclusions The placebo effects observed in antidepressant treatment are influenced by societal wellbeing, suggesting that socionomic sentiment should be taken into account when assessing the effectiveness of psychopharmacological interventions.