Socio-demographic and clinical risk factors of treatment-resistant depression: A Danish population-based cohort study

J Affect Disord. 2020 Jan 15;261:221-229. doi: 10.1016/j.jad.2019.10.005. Epub 2019 Oct 9.


Background: Knowledge of risk factors of treatment-resistant depression (TRD) contributes to understand the underlying mechanisms and to identify patients at risk. However, there is still a lack of studies on how different risk factors associate with TRD. The objective of this study was to determine the independent association of several socio-demographic and clinical risk factors with TRD.

Methods: 194.074 patients with a first-time hospital contact for depression identified in the Danish National Patient Registry (DNPR) from 1996 through 2014 were followed for TRD for 12 months after diagnosis. Socio-demographic and clinical risk factors were identified in nation-wide registries. Data were analyzed using Cox Proportional Hazard Regression and Fine-Gray model for competing mortality risk.

Results: Indicators of disease severity (recurrent depression (adjusted HR (aHR) 1.17 (1.14-1.20)), severity of depression (aHR 2.01 (1.95-2.08)), admission to a psychiatric ward (aHR 2.03 (1.96, 2.10)) were strong risk factors. Aged 65-84 (aHR 1.96 (1.83-2.10)), lost labor market affiliation ((aHR 1.12 (1.08, 1.16)), cohabiting (aHR 1.27 (1.23, 1.30)), comorbid anxiety (aHR 1.18 (1.10-1.27)), insomnia (aHR 1.27 (1.06-1.51)), migraine (aHR 1.42 (1.16-1.73)) and use of psychotropic drugs was also associated with higher rates of TRD.

Limitations: Information on drug use during hospitalization was not available. Information on rating scales could have provided a more precise assessment of symptom severity and treatment response.

Conclusions: Besides indicators of disease severity, other important risk factors associated with TRD are age, lost labor market affiliation, cohabiting with a partner as well as anxiety, insomnia, migraine and the use of psychotropic medications.

Keywords: Antidepressants; Depression; Epidemiology; Major depressive disorder; Population-based study; Treatment-resistant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anxiety Disorders / epidemiology
  • Cohort Studies
  • Demography*
  • Denmark / epidemiology
  • Depression / epidemiology
  • Depressive Disorder, Major / epidemiology*
  • Depressive Disorder, Treatment-Resistant / epidemiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychotropic Drugs / adverse effects
  • Registries
  • Risk Factors*
  • Sleep Initiation and Maintenance Disorders / epidemiology
  • Substance-Related Disorders / epidemiology


  • Psychotropic Drugs