Difficult-to-treat depression: A clinical and research roadmap for when remission is elusive

Aust N Z J Psychiatry. 2019 Feb;53(2):109-118. doi: 10.1177/0004867418808585. Epub 2018 Oct 31.


Objectives: The report considers the pros and cons of the most commonly used conceptual model that forms the basis for most clinical practice guidelines for depression. This model promotes the attainment of sustained symptom remission as the treatment goal based on its well-established prognostic and functional importance. Sustained remission is very unlikely, however, after multiple treatment attempts. Our current model propels many clinicians to continue to change or add treatments despite little chance for remission or full functional restoration and despite the increasing risk of more adverse events from polypharmacy. An alternative 'difficult-to-treat depression' model is presented and considered. It accepts that the treatment aims for some depressed patients may shift to optimal symptom control rather than remission. When difficult-to-treat depression is suspected, the many treatable causes of persistent depression must be assessed and addressed (given the importance of remission when attainable) before difficult-to-treat depression can be ascribed. The clinical and research implications of the difficult-to-treat depression model are discussed.

Conclusion: Suspected difficult-to-treat depression provides a practical basis for considering when to conduct a comprehensive evaluation. Once difficult-to-treat depression is confirmed, treatment may better focus on optimal disease management (symptom control and functional improvement).

Keywords: Treatment-resistant depression; depression; difficult-to-treat depression; managing depression; outcomes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Depressive Disorder, Treatment-Resistant*
  • Disease Management*
  • Humans
  • Models, Psychological