Original Research Difficult to Treat Depression March 23, 2022

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

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

J Clin Psychiatry 2022;83(3):21m14073

ABSTRACT

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.

Continue Reading...

Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.

Subscribe Now

Already a member? Login

Purchase PDF for $40

Members enjoy free PDF downloads on all articles. Join today

  1. Depression and Other Common Mental Disorders. Global Health Estimates. World Health Organization; 2017:1–24.
  2. Mojtabai R, Olfson M. Major depression in community-dwelling middle-aged and older adults: prevalence and 2- and 4-year follow-up symptoms. Psychol Med. 2004;34(4):623–634. PubMed CrossRef
  3. Byers AL, Yaffe K, Covinsky KE, et al. High occurrence of mood and anxiety disorders among older adults: The National Comorbidity Survey Replication. Arch Gen Psychiatry. 2010;67(5):489–496. PubMed CrossRef
  4. Lyness JM, Caine ED, King DA, et al. Psychiatric disorders in older primary care patients. J Gen Intern Med. 1999;14(4):249–254. PubMed CrossRef
  5. Hoover DR, Siegel M, Lucas J, et al. Depression in the first year of stay for elderly long-term nursing home residents in the USA. Int Psychogeriatr. 2010;22(7):1161–1171. PubMed CrossRef
  6. Brodaty H, Luscombe G, Parker G, et al. Early and late onset depression in old age: different aetiologies, same phenomenology. J Affect Disord. 2001;66(2-3):225–236. PubMed CrossRef
  7. Bruce MLMG, McAvay GJ, Raue PJ, et al. Major depression in elderly home health care patients. Am J Psychiatry. 2002;159(8):1367–1374. PubMed CrossRef
  8. Thomas L, Mulsant BH, Solano FX, et al. Response speed and rate of remission in primary and specialty care of elderly patients with depression. Am J Geriatr Psychiatry. 2002;10(5):583–591. PubMed CrossRef
  9. Whyte EM, Basinski J, Farhi P, et al. Geriatric depression treatment in nonresponders to selective serotonin reuptake inhibitors. J Clin Psychiatry. 2004;65(12):1634–1641. PubMed CrossRef
  10. Alexopoulos GS, Canuso CM, Gharabawi GM, et al. Placebo-controlled study of relapse prevention with risperidone augmentation in older patients with resistant depression. Am J Geriatr Psychiatry. 2008;16(1):21–30. PubMed CrossRef
  11. Alexopoulos GS, Chester JG. Outcomes of geriatric depression. Clin Geriatr Med. 1992;8(2):363–376. PubMed CrossRef
  12. Lenze EJ, Schulz R, Martire LM, et al. The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the Cardiovascular Health Study. J Am Geriatr Soc. 2005;53(4):569–575. PubMed CrossRef
  13. Lenze EJ. Comorbidity of depression and anxiety in the elderly. Curr Psychiatry Rep. 2003;5(1):62–67. PubMed CrossRef
  14. Liang CS, Chung CH, Ho PS, et al. Superior anti-suicidal effects of electroconvulsive therapy in unipolar disorder and bipolar depression. Bipolar Disord. 2018;20(6):539–546. PubMed CrossRef
  15. Liang CS, Bai YM, Hsu JW, et al. The risk of sexually transmitted infections following first-episode schizophrenia among adolescents and young adults: a cohort study of 220–545 subjects. Schizophr Bull. 2020;46(4):795–803. PubMed CrossRef
  16. Huang JS, Yang FC, Chien WC, et al. Risk of substance use disorder and its associations with comorbidities and psychotropic agents in patients with autism. JAMA Pediatr. 2021;175(2):e205371. PubMed CrossRef
  17. Chen MH, Lan WH, Hsu JW, et al. Risk of developing type 2 diabetes in adolescents and young adults with autism spectrum disorder: a nationwide longitudinal study. Diabetes Care. 2016;39(5):788–793. PubMed CrossRef
  18. Chen MH, Pan TL, Li CT, et al. Risk of stroke among patients with post-traumatic stress disorder: nationwide longitudinal study. Br J Psychiatry. 2015;206(4):302–307. PubMed CrossRef
  19. Chen MH, Su TP, Chen YS, et al. Attention deficit hyperactivity disorder, tic disorder, and allergy: is there a link? a nationwide population-based study. J Child Psychol Psychiatry. 2013;54(5):545–551. PubMed CrossRef
  20. Cheng CM, Chang WH, Chen MH, et al. Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study. Mol Psychiatry. 2018;23(8):1756–1763.PubMed
  21. Li CT, Bai YM, Huang YL, et al. Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study. Br J Psychiatry. 2012;200(1):45–51. PubMed CrossRef
  22. Gaynes BN, Lux L, Gartlehner G, et al. Defining treatment-resistant depression. Depress Anxiety. 2020;37(2):134–145. PubMed CrossRef
  23. Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003;53(8):649–659. PubMed CrossRef
  24. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. PubMed CrossRef
  25. Kautzky A, Dold M, Bartova L, et al. Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study. Acta Psychiatr Scand. 2019;139(1):78–88. PubMed CrossRef
  26. Beekman AT, de Beurs E, van Balkom AJ, et al. Anxiety and depression in later life: co-occurrence and communality of risk factors. Am J Psychiatry. 2000;157(1):89–95. PubMed CrossRef
  27. Jeste ND, Hays JC, Steffens DC. Clinical correlates of anxious depression among elderly patients with depression. J Affect Disord. 2006;90(1):37–41. PubMed CrossRef
  28. Schoevers RA, Beekman AT, Deeg DJ, et al. Comorbidity and risk-patterns of depression, generalised anxiety disorder and mixed anxiety-depression in later life: results from the AMSTEL study. Int J Geriatr Psychiatry. 2003;18(11):994–1001. PubMed CrossRef
  29. DeLuca AK, Lenze EJ, Mulsant BH, et al. Comorbid anxiety disorder in late life depression: association with memory decline over four years. Int J Geriatr Psychiatry. 2005;20(9):848–854. PubMed CrossRef
  30. Morimoto SS, Kanellopoulos D, Manning KJ, et al. Diagnosis and treatment of depression and cognitive impairment in late life. Ann N Y Acad Sci. 2015;1345(1):36–46. PubMed CrossRef
  31. Brenner P, Brandt L, Li G, et al. Substance use disorders and risk for treatment resistant depression: a population-based, nested case-control study. Addiction. 2020;115(4):768–777. PubMed CrossRef
  32. Brenner P, Brandt L, Li G, et al. Treatment-resistant depression as risk factor for substance use disorders-a nation-wide register-based cohort study. Addiction. 2019;114(7):1274–1282. PubMed CrossRef
  33. Wu LT, Blazer DG. Substance use disorders and psychiatric comorbidity in mid and later life: a review. Int J Epidemiol. 2014;43(2):304–317. PubMed CrossRef
  34. Kuerbis A, Sacco P, Blazer DG, et al. Substance abuse among older adults. Clin Geriatr Med. 2014;30(3):629–654. PubMed CrossRef
  35. Wells KB, Golding JM, Burnam MA. Psychiatric disorder in a sample of the general population with and without chronic medical conditions. Am J Psychiatry. 1988;145(8):976–981. PubMed CrossRef
  36. Anderson RJ, Freedland KE, Clouse RE, et al. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001;24(6):1069–1078. PubMed CrossRef
  37. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15(9):505–522. PubMed CrossRef
  38. Fiske A, Wetherell JL, Gatz M. Depression in older adults. Annu Rev Clin Psychol. 2009;5(1):363–389. PubMed CrossRef
  39. Chen MH, Pan TL, Hsu JW, et al. Attention-deficit hyperactivity disorder comorbidity and antidepressant resistance among patients with major depression: a nationwide longitudinal study. Eur Neuropsychopharmacol. 2016;26(11):1760–1767. PubMed CrossRef
  40. Chan YE, Chen MH, Tsai SJ, et al. Treatment-resistant depression enhances risks of dementia and Alzheimer’s disease: a nationwide longitudinal study. J Affect Disord. 2020;274:806–812. PubMed CrossRef