Interaction patterns of internalized and perceived stigma with antidepressant adverse reactions on medication adherence in major depressive disorder: A prospective cohort study.

BACKGROUND

Major depressive disorder (MDD) is a leading global cause of disease burden, and suboptimal medication adherence is a primary driver of treatment failure. Both depression stigma and antidepressant adverse drug reactions (ADRs) are established barriers to adherence, but their interactive effects and temporal dynamics in MDD remain poorly characterized.

METHODS

The subjects of this prospective cohort study were MDD patients from the Depression Cohort in China. Medication adherence, stigma, and ADRs were repeated assessed at baseline and weeks 4, 8, 12, 24, 48, and 72 using the Medication Adherence Rating Scale, Depression Stigma Scale, and Side-effect Rating Scale for Antidepressants, respectively. Generalized additive mixed model (GAMM) was employed to explore the interaction between stigma and ADRs, while analyzing its temporal effect on medication adherence.

RESULTS

Among 1770 patients with a mean (SD) age of 28.74 (7.90) years, 68.53% were female. GAMMs showed significant nonlinear interactions between internalized stigma (IS) and ADRs, and between perceived stigma (PS) and ADRs (both P < 0.001; edf = 6.309 and 8.301). IS predominantly impaired adherence when ADRs were severe, whereas PS exerts the strongest negative effect when ADRs were mild. The study found no statistical evidence of temporal heterogeneity (P = 0.175 and 0.673, respectively).

CONCLUSIONS

Stigma and ADRs jointly influence antidepressant adherence through a stable, nonlinear interaction pattern. The divergent effects of IS and PS across ADRs severity levels support differentiated intervention strategies: prioritizing ADRs management for patients with high IS, and providing early psychosocial support for those with high PS.