Abstract
BACKGROUND: Relapse remains a major challenge in managing mental disorders, particularly in low-resource settings where empirical evidence is limited. This study estimated relapse prevalence and associated factors, and examined whether disorder type and psychological well-being moderated, and self-stigma mediated, the medication adherence-relapse link. METHODS: A cross-sectional study was conducted among 310 outpatients at Ndera Neuropsychiatric Teaching Hospital. Data were collected using structured questionnaires and validated scales measuring relapse, self-stigma, medication adherence, and psychological well-being. Chi-square tests assessed associations, while binary logistic regression identified independent predictors using SPSS version 29. RESULTS: Relapse prevalence was 76.1% in schizophrenia, 69.4% in bipolar disorder, 47.8% in depression, and 64.9% in substance misuse. Disorder type strongly predicted relapse: schizophrenia (AOR = 3.01, 95% CI: 1.28-7.09) and bipolar disorder (AOR = 2.74, 95% CI: 1.19-6.31) showed significantly higher risk than depression. Substance misuse, self-stigma, poor medication adherence, and low psychological well-being were associated with relapse in crude models but lost significance after adjustment. Moderation analysis revealed that psychological well-being significantly strengthened adherence's protective effect, reducing relapse from 91.7% at low adherence to 34.8% at high adherence. Disorder type shaped adherence effects: high adherence reduced relapse only in schizophrenia, with inconsistent effects in other disorders. Self-stigma did not mediate the adherence-relapse link. CONCLUSION: Medication adherence alone showed inconsistent effects; its protective role was pronounced in schizophrenia and among patients with high psychological well-being. Relapse prevention should prioritize enhancing adherence in schizophrenia and integrating psychological well-being interventions. Tailoring management to diagnostic subgroups is essential for improving outcomes.