Major depressive disorder relapse in primary care

Background: Major depressive disorder (MDD) is a chronic, recurrent illness and a leading cause of disability worldwide. Despite the effectiveness of acute-phase treatments, relapse remains both highly prevalent and insufficiently addressed in primary care, contributing to fragmented care, reduced quality of life, and an increasing economic burden. This thesis examined relapse in MDD through three complementary studies, integrating a systematic review, population-based pharmacoepidemiology, and health economic modeling within the Canadian primary care context. Methods: Study 1 undertook a systematic review and meta-analysis of 35 studies to estimate relapse incidence and compare the effectiveness of pharmacologic, psychological, and combined interventions in primary care. Study 2 utilized linked administrative health data from Newfoundland and Labrador (2010-2020) to examine antidepressant reinitiation after ?6-month gaps, used as a proxy indicator for relapse among adults discharged from hospital with MDD. Time-varying Cox regression models were employed to estimate hazard ratios (HRs) by treatment type, age, sex, and socioeconomic status. Study 3 developed a Markov model to compare the lifetime cost-utility of cognitive behavioral therapy (CBT) versus mindfulness-based cognitive therapy (MBCT) for relapse prevention, from both public payer and societal perspectives, in alignment with Canadian Drug Agency (CDA) guidelines. Results: Across all studies, relapse or antidepressant reinitiation occurred in approximately 30-60% of patients within one year, underscoring the recurrent nature of MDD. In Study 2, 61% of patients reinitiated antidepressants following hospitalization, with lower relapse risk among individuals receiving combination therapy compared to monotherapy. Age and income emerged as significant modifiers of relapse trajectories. Study 3 identified CBT as the more cost-effective option under Canadian public payer assumptions (incremental cost-effectiveness ratio below commonly accepted willingness-to-pay thresholds), while MBCT remained a viable alternative, particularly in group-delivery contexts. Conclusions: Relapse in MDD is common, insufficiently managed, and influenced by pharmacologic, psychosocial, biological and sociodemographic factors. Psychological interventions such as CBT and MBCT are both clinically effective and economically defensible options for sustained remission. This thesis advocates a health-system-level reframing of MDD care—embedding relapse prevention within longitudinal, stepped, and publicly funded primary care pathways.