What happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies

J Affect Disord. 2009 Jul;116(1-2):4-11. doi: 10.1016/j.jad.2008.10.014. Epub 2008 Nov 12.


Background: Treatment-resistant depression (TRD) is relatively common and accounts for a large proportion of the overall burden caused by depression. We conducted a systematic review of outcome studies of TRD in order to summarise findings on the longer term outcome of TRD and make recommendations.

Methods: Studies were identified through MEDLINE (1960--June Week 1 2008), EMBASE (1974--June Week 1 2008) and PsycINFO (1967--June Week 1 2008) searches. We included studies that followed adults with highly probable TRD for a minimum of 6 months. Statistical analyses were conducted on selected outcome variables whenever possible. Methodological heterogeneity of studies prohibited formal meta-analysis.

Results: We identified nine outcome studies with a total of 1279 participants and follow-up duration of between 1 and 10 years. In the short term, TRD was highly recurrent with as many as 80% of those requiring multiple treatments relapsing within a year of achieving remission. For those with a more protracted illness, the probability of recovery within 10 years was about 40%. TRD was also associated with poorer quality of life and increased mortality.

Limitations: Included primary studies were heterogeneous.

Conclusions: TRD is associated with poorer clinical outcome, particularly among those who require multiple antidepressant medications. The main limitations of the review arise from the variability in recruitment procedures, definitions and outcome assessments of the original studies. We recommend further follow-up studies of carefully identified samples in order to gain a more detailed understanding of this domain of depression and plan effective interventions.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects*
  • Clinical Trials as Topic
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / mortality
  • Depressive Disorder / psychology
  • Drug Therapy, Combination
  • Humans
  • Prognosis
  • Quality of Life / psychology
  • Recurrence
  • Remission Induction
  • Treatment Failure


  • Antidepressive Agents