Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression

J Clin Psychiatry. 2006 May;67(5):688-95. doi: 10.4088/jcp.v67n0501.


Background: Treatment-resistant depression (TRD) is a long-term, disabling illness. We report on the characteristics and outcomes of a large cohort of patients with a level of treatment resistance that is very substantial and who were treated for 2 years with standard care.

Method: This 2-year prospective, multicenter, observational study (patients enrolled from January 2001 through July 2004) tracked the outcomes of 124 patients with treatment-resistant, nonpsychotic major depressive disorder (N = 109) or bipolar depressed phase disorder (N = 15) who received treatment as usual (TAU) (i.e., any therapeutic regimen agreed to by patients and psychiatrists, including medications, electroconvulsive therapy [ECT], and psychotherapy). Treatments could be adjusted, started, and stopped as necessary. The primary outcome, treatment response, was defined a priori as > or = 50% improvement from baseline as measured by the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR-30). Remission was defined as an IDS-SR-30 score of < or = 14. The Medical Outcomes Study (MOS) 36-item Short Form Health Survey (SF-36) was used to monitor quality-of-life changes.

Results: The 12- and 24-month IDS-SR-30 response rates were 11.6% (13/112) and 18.4% (19/103), respectively. Of the 13 responders at 12 months, only 5 were responders at 24 months. The 12- and 24-month IDS-SR-30 remission rates were 3.6% (4/112) and 7.8% (8/103), respectively. Only 1 of the 4 12-month remitters was also a remitter at 24 months. The SF-36 indicated globally poor quality of life in this sample.

Conclusions: Despite the wide range of treatment options available for depression, the response rates, remission rates, and quality-of-life results in this study show that most patients with a substantial degree of treatment resistance continue to have significant symptomatology and functional disability when receiving TAU.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / psychology
  • Bipolar Disorder / therapy*
  • Cohort Studies
  • Depressive Disorder / diagnosis
  • Depressive Disorder / psychology
  • Depressive Disorder / therapy
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / psychology
  • Depressive Disorder, Major / therapy*
  • Drug Resistance
  • Electroconvulsive Therapy
  • Health Status
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Personality Inventory
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Psychotherapy
  • Psychotropic Drugs / therapeutic use
  • Quality of Life
  • Recurrence
  • Surveys and Questionnaires
  • Treatment Outcome


  • Antidepressive Agents
  • Psychotropic Drugs