Current Psychiatry Reports

, Volume 9, Issue 6, pp 449–459 | Cite as

The STAR*D project results: A comprehensive review of findings

  • Diane WardenEmail author
  • A. John Rush
  • Madhukar H. Trivedi
  • Maurizio Fava
  • Stephen R. Wisniewski


The Sequenced Treatment Alternatives to Relieve Depression trial enrolled outpatients with nonpsychotic major depressive disorder treated prospectively in a series of randomized controlled trials. These were conducted in representative primary and psychiatric practices. Remission rates for treatment steps 1 to 4 based on the 16-item Quick Inventory of Depressive Symptomatology-Selfreport were 37%, 31%, 14%, and 13%, respectively. There were no differences in remission rates or times to remission among medication switch or among medication augmentation strategies at any treatment level. Participants who required increasing numbers of treatment steps showed greater depressive illness burden and increasingly greater relapse rates in the naturalistic follow-up period (40%–71%). Prognosis was better at all levels for participants who entered follow-up in remission as opposed to those who entered with response without remission. These results highlight the prevalence of treatment-resistant depression and suggest potential benefit for using more vigorous treatments in the earlier steps.


Remission Rate Mirtazapine Depressive Symptomatology Cognitive Therapy Treatment Step 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Murray CJ, Lopez AD: Evidence-based health policy—lessons from the Global Burden of Disease Study. Science 1996, 274:740–743.PubMedCrossRefGoogle Scholar
  2. 2.
    Kessler RC, Berglund P, Demler O, et al.: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003, 289:3095–3105.PubMedCrossRefGoogle Scholar
  3. 3.
    Greenberg PE, Kessler RC, Birnbaum HG, et al.: The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry 2003, 64:1465–1475.PubMedCrossRefGoogle Scholar
  4. 4.
    Akiskal HS, Akiskal K: Cyclothymic, hyperthymic and depressive temperaments as subaffective variant of mood disorders. In American Psychiatric Press Review of Psychiatry. Edited by Tasman A. Washington, DC: American Psychiatric Press; 1992:43–62.Google Scholar
  5. 5.
    Kocsis JH, Klein DN: Diagnosis and Treatment of Chronic Depression. New York: Guilford Press; 1995.Google Scholar
  6. 6.
    Schulberg HC, Katon W, Simon GE, Rush AJ: Treating major depression in primary care practice: an update of the Agency for Health Care Policy and Research Practice Guidelines. Arch Gen Psychiatry 1998, 55:1121–1127.PubMedCrossRefGoogle Scholar
  7. 7.
    Ballenger JC: Clinical guidelines for establishing remission in patients with depression and anxiety. J Clin Psychiatry 1999, 60(Suppl 22):29–34.PubMedGoogle Scholar
  8. 8.
    Trivedi MH, DeBattista C, Fawcett J, et al.: Developing treatment algorithms for unipolar depression in cyberspace: International Psychopharmacology Algorithm Project (IPAP). Psychopharmacol Bull 1998, 34:355–359.PubMedGoogle Scholar
  9. 9.
    Hirschfeld RM, Dunner DL, Keitner G, et al.: Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination. Biol Psychiatry 2002, 51:123–133.PubMedCrossRefGoogle Scholar
  10. 10.
    Rush AJ, Kraemer HC, Sackeim HA, et al.: Report by the ACNP Task Force on Response and Remission in Major Depressive Disorder. Neuropsychopharmacology 2006, 31:1841–1853.PubMedCrossRefGoogle Scholar
  11. 11.
    Depression Guideline Panel: Clinical Practice Guideline, Number 5: Depression in Primary Care: Volume 2. Treatment of Major Depression. Rockville, MD: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; 1993.Google Scholar
  12. 12.
    Kessler RC, McGonagle KA, Zhao S, et al.: Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994, 51:8–19.PubMedGoogle Scholar
  13. 13.
    Weissman MM, Leaf PJ, Bruce ML, Florio L: The epidemiology of dysthymia in five communities: rates, risks, comorbidity, and treatment. Am J Psychiatry 1988, 145:815–819.PubMedGoogle Scholar
  14. 14.
    Lin EH, Katon WJ, Simon GE, et al.: Achieving guidelines for the treatment of depression in primary care. Is physician education enough? Med Care 1997, 35:831–842.PubMedCrossRefGoogle Scholar
  15. 15.
    Rost K, Nutting P, Smith JL, et al.: Managing depression as a chronic disease: a randomised trial of ongoing treatment in primary care. BMJ 2002, 325:934.PubMedCrossRefGoogle Scholar
  16. 16.
    Rush AJ, Trivedi M, Carmody TJ, et al.: One-year clinical outcomes of depressed public sector outpatients: a benchmark for subsequent studies. Biol Psychiatry 2004, 56:46–53.PubMedCrossRefGoogle Scholar
  17. 17.
    Schulberg HC, Block MR, Madonia MJ, et al.: The ‘usual care’ of major depression in primary care practice. Arch Fam Med 1997, 6:334–339.PubMedCrossRefGoogle Scholar
  18. 18.
    Greden JF: Clinical prevention of recurrent depression. The need for paradigm shifts. In Treatment of Recurrent Depression. Edited by Greden JF. Washington, DC: American Psychiatric Press; 2001:143–170.Google Scholar
  19. 19.
    Fava M, Rush AJ, Trivedi MH, et al.: Background and rationale for the sequenced treatment alternatives to relieve depression (STAR*D) study. Psychiatr Clin North Am 2003, 26:457–494.PubMedCrossRefGoogle Scholar
  20. 20.
    Rush AJ, Fava M, Wisniewski SR, et al.: Sequenced Treatment Alternatives to Relieve Depression (STAR*D): rationale and design. Control Clin Trials 2004, 25:119–142.PubMedCrossRefGoogle Scholar
  21. 21.
    Rush AJ, Trivedi MH, Wisniewski SR, et al.: Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006, 163:1905–1917.PubMedCrossRefGoogle Scholar
  22. 22.
    Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960, 23:56–62.PubMedCrossRefGoogle Scholar
  23. 23.
    Lavori PW, Rush AJ, Wisniewski SR, et al.: Strengthening clinical effectiveness trials: equipoise-stratified randomization. Biol Psychiatry 2001, 50:792–801.PubMedCrossRefGoogle Scholar
  24. 24.
    Mundt JC: Interactive voice response systems in clinical research and treatment. Psychiatr Serv 1997, 48:611–612.PubMedGoogle Scholar
  25. 25.
    Rush AJ, Trivedi MH, Ibrahim HM, et al.: The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003, 54:573–583. [Published erratum appears in Biol Psychiatry 2003, 54:585.]PubMedCrossRefGoogle Scholar
  26. 26.
    Rush AJ, Bernstein IH, Trivedi MH, et al.: An evaluation of the Quick Inventory of Depressive Symptomatology and the Hamilton Rating Scale for Depression: a Sequenced Treatment Alternatives to Relieve Depression trial report. Biol Psychiatry 2006, 59:493–501.PubMedCrossRefGoogle Scholar
  27. 27.
    Trivedi MH, Rush AJ, Ibrahim HM, et al.: The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self-Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation. Psychol Med 2004, 34:73–82.PubMedCrossRefGoogle Scholar
  28. 28.
    Trivedi MH, Rush AJ, Wisniewski SR, et al.: Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006, 163:28–40.PubMedCrossRefGoogle Scholar
  29. 29.
    Trivedi MH, Rush AJ, Gaynes BN, et al.: Maximizing the adequacy of medication treatment in controlled trials and clinical practice: STAR*D measurement-based care. Neuropsychopharmacology 2007 [Epub ahead of print].Google Scholar
  30. 30.
    Wisniewski SR, Rush AJ, Balasubramani GK, et al.: Self-rated global measure of the frequency, intensity, and burden of side effects. J Psychiatr Pract 2006, 12:71–79.PubMedCrossRefGoogle Scholar
  31. 31.
    Wisniewski SR, Eng H, Meloro L, et al.: Web-based communications and management of a multi-center clinical trial: the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project. Clin Trials 2004, 1:387–398.PubMedCrossRefGoogle Scholar
  32. 32.
    Wisniewski SR, Fava M, Trivedi MH, et al.: Acceptability of second-step treatments to depressed outpatients: a STAR*D report. Am J Psychiatry 2007, 164:753–760.PubMedCrossRefGoogle Scholar
  33. 33.
    Rush AJ, Trivedi MH, Wisniewski SR, et al.: Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 2006, 354:1231–1242.PubMedCrossRefGoogle Scholar
  34. 34.
    Fava M, Papakostas GI, Petersen T, et al.: Switching to bupropion in fluoxetine-resistant major depressive disorder. Ann Clin Psychiatry 2003, 15:17–22.PubMedCrossRefGoogle Scholar
  35. 35.
    Fava M, McGrath PJ, Sheu WP: Switching to reboxetine: an efficacy and safety study in patients with major depressive disorder unresponsive to fluoxetine. J Clin Psychopharmacol 2003, 23:365–369.PubMedCrossRefGoogle Scholar
  36. 36.
    Saiz-Ruiz J, Ibanez A, Diaz-Marsa M, et al.: Efficacy of venlafaxine in major depression resistant to selective serotonin reuptake inhibitors. Prog Neuropsychopharmacol Biol Psychiatry 2002, 26:1129–1134.PubMedCrossRefGoogle Scholar
  37. 37.
    Thase ME, Rush AJ: Treatment-resistant depression. In Psychopharmacology: Fourth Generation of Progress. Edited by Bloom FE, Kupfer DJ. New York: Raven Press; 1995:1081–1097.Google Scholar
  38. 38.
    Trivedi MH, Fava M, Wisniewski SR, et al.: Medication augmentation after the failure of SSRIs for depression. N Engl J Med 2006, 354:1243–1252.PubMedCrossRefGoogle Scholar
  39. 39.
    Thase ME, Friedman ES, Biggs MM, et al.: Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry 2007, 164:739–752.PubMedCrossRefGoogle Scholar
  40. 40.
    Hollon SD, DeRubeis RJ, Shelton RC, et al.: Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Arch Gen Psychiatry 2005, 62:417–422.PubMedCrossRefGoogle Scholar
  41. 41.
    Keller MB, McCullough JP, Klein DN, et al.: A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000, 342:1462–1470.PubMedCrossRefGoogle Scholar
  42. 42.
    Thase ME, Friedman ES, Berman SR, et al.: Is cognitive behavior therapy just a ‘nonspecific’ intervention for depression? A retrospective comparison of consecutive cohorts treated with cognitive behavior therapy or supportive counseling and pill placebo. J Affect Disord 2000, 57:63–71.PubMedCrossRefGoogle Scholar
  43. 43.
    Fava M, Rush AJ, Wisniewski SR, et al.: A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. Am J Psychiatry 2006, 163:1161–1172.PubMedCrossRefGoogle Scholar
  44. 44.
    Nierenberg AA, Fava M, Trivedi MH, et al.: A comparison of lithium and T3 augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry 2006, 163:1519–1530.PubMedCrossRefGoogle Scholar
  45. 45.
    McGrath PJ, Stewart JW, Fava M, et al.: Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 2006, 163:1531–1541.PubMedCrossRefGoogle Scholar
  46. 46.
    Fava M: Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 2003, 53:649–659.PubMedCrossRefGoogle Scholar
  47. 47.
    Sackeim HA: The definition and meaning of treatment-resistant depression. J Clin Psychiatry 2001, 62(Suppl 16):10–17.PubMedGoogle Scholar
  48. 48.
    Souery D, Amsterdam J, de Montighny C, et al.: Treatment resistant depression: methodological overview and operational criteria. Eur Neuropsychopharmacol 1999, 9:83–91.PubMedCrossRefGoogle Scholar
  49. 49.
    Warden D, Trivedi MH, Wisniewski SR, et al.: Pretreatment predictors of attrition during initial (citalopram) treatment for depression: a STAR*D report. Am J Psychiatry 2007, 164:1189–1197.PubMedCrossRefGoogle Scholar
  50. 50.
    Wagner HR, Burns BJ, Broadhead WE, et al.: Minor depression in family practice: functional morbidity, co-morbidity, service utilization and outcomes. Psychol Med 2000, 30:1377–1390.PubMedCrossRefGoogle Scholar
  51. 51.
    Simon GE, Lin EH, Katon W, et al.: Outcomes of “inadequate” antidepressant treatment. J Gen Intern Med 1995, 10:663–670.PubMedCrossRefGoogle Scholar
  52. 52.
    Gaynes BN, Rush AJ, Trivedi M, et al.: A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial. Gen Hosp Psychiatry 2005, 27:87–96.PubMedCrossRefGoogle Scholar
  53. 53.
    Gaynes BN, Rush AJ, Trivedi MH, et al.: Major depression symptoms in primary care and psychiatric care settings: a cross-sectional analysis. Ann Fam Med 2007, 5:126–134.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  • Diane Warden
    • 1
    Email author
  • A. John Rush
  • Madhukar H. Trivedi
  • Maurizio Fava
  • Stephen R. Wisniewski
  1. 1.Department of PsychiatryThe University of Texas Southwestern Medical Center at DallasDallasUSA

Personalised recommendations