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

Po Chun Lin, Ta Chuan Yeh, Ya Mei Bai, Ju Wei Hsu, Kai Lin Huang, Nai Ying Ko, Che Sheng Chu, Hsuan Te Chu, Shih Jen Tsai, Tzeng Ji Chen, Chih Sung Liang, Mu Hong Chen

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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.

Original languageEnglish
Article number21m14073
JournalJournal of Clinical Psychiatry
Issue number3
Publication statusPublished - 2022 May

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health


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