Sequenced Treatment Alternatives to Relieve Depression (Star*D/Adult)

Principal Investigators: Steven Hollon, Ph.D., Richard C. Shelton, M.D.

Centerstone and Vanderbilt University were part of a nationwide study on the most effective ways to relieve depression. Referred to as STAR*D, this study was the largest and longest study of its kind. It has set a new standard for depression treatment with 100% remission being the goal. In the past, simple reduction of symptoms has been the standard measurement in depression trials. Following the STAR*D protocols, researchers found that they can obtain a 70% rate of complete remission rate for clients with depression.

Depression is a common mental illness in the United States with approximately 8% of the US population experiencing depression in a given year (NIMH). A serious illness, major depressive disorder is the leading cause of disability for Americans age 15-44. There are many different treatments available for depression – from cognitive behavioral therapy to electroconvulsive therapy to 20 different kinds of medications.

The STAR*D trial looked at the efficacy of one type of psychotherapy (Cognitive Behavioral Therapy) and 11 different pharmacological therapies: citalapram (Celexa), sertraline (Zoloft), bupropion-SR (Wellbutrin), venlafaxine-ZR (Effexor), buspirone (BuSpar) or bupropion (Wellbutrin) added to citalopram, mirtazapine (Remeron), nortriptyline (Aventyl or Pamelor), lithium, triiodthyronine (T3), the MAOI tranylcypromine (Parnate), and a combination of venlafaxine XR (Effexor XR) + mirtazapine (Remeron). A flowchart of the complete protocol for the study is available here.

A sample of STAR*D trial findings:

• The use of citalapram resulted in only 30% of clients achieving total remission of depression (Trivedi et al, 2006).
• CBT has been shown to be as effective as medications for clients not achieving remission with citalopram (Thase, et al, 2007).
• Remission of maternal depression has a positive effect on both mothers and children with depression (Weissman, et al, 2006).
• Children with depressed mothers are at high risk for disruptive and anxiety disorders (Pilowski, et al, 2006).
• When citalopram doesn’t work on its own, adding either sustained-release bupropion or buspirone can be helpful, but bupropion is more effective with less side effects (Trivedi, 2006)
• When a patient hasn’t responded to two different kinds of antidepressants, they have less than 20% chance of achieving remission with other medications (Rush et al, 2006).
• If using an SSRI was not effective, approximately one in four patients had a remission of symptoms after switching to another antidepressant (either bupropion-SR, sertraline, or venlafaxine-XR). There was no significant difference in the effectiveness of these medications (Rush et al, 2006).
• If a patient has depression and a substance use disorder, they are at a greater suicide risk. They are also more likely to be young, male, divorced or never married and have more depressive symptoms (Davis et al, 2006).
• If a client has recurrent depression, they are less likely to have chronic depression (Hollon, et al, 2006).
• Specific genetic variants of a serotonin receptor (2A) predict response to citalopram, while a variation of a gene called CREB1 predicts new onset suicidal thoughts after starting citalopram.
• Assessing a client’s score on the Health Related Quality of Life index can assist a practitioner in determining the severity of depression (Trivedi, 2006).

Numerous publications have come out of the STAR*D results. For a list of the publications, please visit clinicaltrials.gov. Abstracts of all of the papers are available, including some free full-text versions.

References
Davis, L.L., Frazier, E., Husain, M.M., Warden, D., Trivedi, M., Fava, M., et al (2006). Substance use disorder comorbidity in major depressive disorder: A confirmatory analysis of the STAR*D cohort. American Journal of Addiction. 2006 Jul-Aug;15(4):278-85. 

Hollon, S.D., Shelton, R.C., Wisniewski, S., Warden, D., Biggs, M.M., Friedman, E.S., et al (2006). Presenting characteristics of depressed outpatients as a function of recurrence: Preliminary findings from the STAR*D clinical trial. Journal of Psychiatric Research. 40(1): 59-69.

Kessler, R.C., Chiu, W.T., Demler, O., & Walters, E.E. (2005). Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry. 62(6): 617-627.

Rush, A.J., Trivedi, M.H., Wisniewski, S.R., Nierenberg, A., Stewart, J.W., Warden, D., et al. (2006). Acute and longer-term outcomes in depressed outpatients who required one or several treatment steps: A STAR*D report. American Journal of Psychiatry. 163(11): 1905-1917.

Rush, A.J., Trivedi, M.H., Wisniewski, S.R., Stewart, J.W., Nierenberg, A.A., Thase, M.E., et al (2006). Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. New England Journal of Medicine. 354(12): 1231-1242.

Trivedi, M.H., Rush, A.J., Wisniewski, S.R., Nierenberg, A.A., Warden, D., Ritz, L., et al (2006). Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice. American Journal of Psychiatry. 163(1): 28-40.

Trivedi, M.H., Rush, A.J., Wisniewski, S.R., Warden, D., McKinney, W., Downing, M., et al (2006). Factors associated with health-related quality of life among outpatients with major depressive disorder: a STAR*D report. Journal of Clinical Psychiatry. 67(2):185-95.

Pilowsky, D.J., Wickramaratne, P.J., Rush, A.J., Hughes, C.W., Garber, J., Malloy, E., et al (2006) Children of currently depressed mothers: A STAR*D ancillary study. Journal of Clinical Psychiatry. 67(1): 126-136.

Weissman, M.M., Pilowsky, D.J., Wickramaratne, P.J., Talati, A., Wisniewski, S.R., Fava,, et al (2006). Remissions in maternal depression and child psychopathology: a STAR*D-child report. Journal of the American Medical Association. 295(12):1389-1398.