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

October 22, 2008

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.