Risk factors for treatment resistance in unipolar depression: a systematic review

J Affect Disord. 2015 Jan 15;171:137-41. doi: 10.1016/j.jad.2014.09.020. Epub 2014 Oct 8.


Background: Treatment resistant depression is a complex disorder and an important source of morbidity and mortality. Identification of risk factors of resistance may be useful to improve early recognition as well as treatment selection and prediction of outcome in patients with depression.

Methods: The aim of this paper was to review the current status of knowledge regarding risk factors of treatment resistance in unipolar depression, in patients who failed to respond to at least two successive and adequate antidepressant treatments.

Results: Systematic literature search yielded 8 publications exploring clinical and biological factors. Specific psychiatric comorbidities, psychosocial factors, clinical characteristics of the depressive episode and biological markers emerge as possible risk factor for treatment resistant depression.

Limitations: Due to the lack of objective definition and diagnostic criteria for treatment resistant depression, and the paucity of reports on risk factors, our review only summarized a small number of studies.

Conclusion: Future investigations of risk factors should help to improve the understanding of the mechanisms underlying resistance in mood disorders and contribute to improve their therapeutic management.

Keywords: Treatment resistance-depression-risk factors.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Depressive Disorder, Treatment-Resistant / complications
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Depressive Disorder, Treatment-Resistant / psychology*
  • Humans
  • Medication Adherence / psychology
  • Medication Adherence / statistics & numerical data
  • Mental Disorders / complications
  • Mental Disorders / psychology
  • Risk Factors


  • Antidepressive Agents