Anhedonia is a core symptom of major depression and a key prognostic factor that is often poorly explored in clinical trials of major depressive disorder (MDD). Beyond symptomatic remission, psychosocial functioning also reveals difficulty in achieving remission in patients with MDD. The main objective of this study was to explore the interrelationships between social functioning and anhedonia on a longitudinal basis.

In total, 1570 outpatients treated for MDD with agomelatine were included. Severity of depression and levels of anhedonia and of psychosocial functioning were assessed at inclusion and at 10–14 weeks, with specific standardized scales (MADRS, QFS, SHAPS, CGI). Multivariate regression and mediation analyses were performed.

Using multivariate regression, we showed that improvement of anhedonia was the strongest predictor of improvement in psychosocial functioning (odds ratio=7.3 [4.3–12.1] P<0.0001). In addition, mediation tests confirmed that the association between improvement of depressive symptoms and improvement of social functioning was significantly underpinned by the improvement of anhedonia over time. Finally, we explored the determinants of the dissociation of the response, i.e., the persistence of psychosocial dysfunctioning despite a symptomatic response to antidepressant treatment, which remains a widespread situation in clinical practice. We showed that this dissociation was strongly predicted by persistence of anhedonia.

Our results suggest that anhedonia is one of the strongest predictors of psychosocial functioning, along with symptomatic remission, and should be carefully assessed by health professionals, in order to optimize pharmacological as well as non-pharmacological management of depression.