Early Antidepressant Resistance in Late-Onset Major Depressive Disorder: A Nationwide Population-Based Cohort Study

Background: The association of treatment resistance with physical and psychiatric comorbidities remains unclear in elderly patients with late-onset major depressive disorder (MDD). Methods: Participants were selected from the Taiwan National Health Insurance Research Database. We included patients aged ≥ 65 years with first-episode MDD (ICD-9-CM codes: 296.2X and 296.3X) between January 1, 2001, and December 31, 2010. All participants were followed for 1 year to investigate the incidence of treatment resistance. Treatment-resistant depression (TRD) was defined as unresponsiveness to at least 2 antidepressants, and treatment-resistant tendency (TRT) was defined as unresponsiveness to the first antidepressant. Physical comorbidities were assessed with the Charlson Comorbidity Index (CCI). Results: 27,189 patients with late-onset MDD were included, among whom 16.6% had the diagnosis of anxiety disorders, 1.5% had alcohol use disorders, and 1.6% had substance use disorder. For physical comorbidities, only 16.6% of patients had a CCI score of 0. During the first year of treatment, 22.1% of patients met TRT criteria, and 1.6% developed TRD. Anxiety disorders (odds ratio: 2.06; 95% confidence interval [CI], 1.67–2.53), substance use disorders (2.11; 95% CI, 1.26–3.53), and higher CCI scores (1.06; 95% CI, 1.01–1.10) were significantly associated with TRD, while anxiety disorders (1.44; 95% CI, 1.34–1.55) and higher CCI scores (1.06; 95% CI, 1.05–1.08) were significantly associated with TRT. Conclusions: Approximately one-fourth of elderly patients responded poorly to the first antidepressant treatment during the first year of late-onset MDD. Psychiatric comorbidities were more associated with the risk of early TRT than were physical comorbidities.