STAR*D Objectives Compare relative efficacy of different treatment

options

– Goal is REMISSION, not just “response”

– Less than half of patients with depression remit with a single antidepressant

– Randomized comparisons of treatment options will define the next best step following previous treatment failure(s)

Identify predictors of remission to treatments Utilize simple self-reports as tools to improve

patient collaboration and objectively evaluate treatment response

Rush AJ, et al. Control Clin Trials. 2004;25:119-142.

STAR*D Study Overview N = 4000 outpatients aged 18 to 75 years old Primary diagnosis of nonpsychotic major

depressive disorder, confirmed by study clinician Most Axis I comorbidities, other general medical

conditions allowed Treatment setting: specialty and primary care HRSD17 score ≥14 at study entry 12–14 weeks per treatment level; 1-year

naturalistic follow-up Equipoise-stratified, randomized design allowed

patients to select treatment strategy and allowed randomization to different treatment options within the selected strategy

Rush AJ, et al. Control Clin Trials. 2004;25:119-142.

Baseline Demographics

Level 1 Baseline Characteristics of Enrolled Participants (N = 3793): Demographics (03/04)

Primary Care

N = 1560

Specialty Care

N = 2233

Total

N = 3793

Age–Mean (SD) 44 (13) 38 (13) 40 (13)

Female 65% 60% 62%

Race

% white% African American% other% Hispanic

67%21%12%16%

76%14%10%10%

72%17%11%12%

Trivedi MH, et al. Am J Psychiatry. 2006;163:28-40. Courtesy of A. John Rush, MD.

Baseline Characteristics

Level 1 Baseline Characteristics (N = 3793): Psychiatric History (03/04)

Primary Care

N = 1560

Specialty Care

N = 2233

Total

N = 3793

Age at onset (years) 42 (14) 37 (13) 39 (13)

Number of MDEs (including current episode)

6 (10) 6 (12) 6 (11)

Length of current episode (months)

21 (41) 17 (42) 18 (42)

Length of illness (years)

16 (14) 15 (13) 15 (13)

MDEs = major depressive episodes.Trivedi MH, et al. Am J Psychiatry. 2006;163:28-40. Courtesy of A. John Rush, MD.

STAR*D Participant Flow into Level 1Screened

(N = 4790)

Ineligible (163) or did not consent (613) (n =

749)

Exit(n = 592)

Follow-up(n = 1083)

Level 2(n = 1201)

a HAM-D = 17-item Hamilton Depression Rating Scale. Adapted from Trivedi MH, et al. Am J Psychiatry. 2006;163:28-40.

Failed to return(n = 234)

Enrolled in Level 1

(n = 4041)

HAM-D score >14

(n = 3110)

Eligible for analysis(n = 2876)

HAM-D score <14a

(n = 607)or HAM-D missing

(n = 324)

SWITCH OPTIONSRandomized

STAR*D Defining Evidence for Protocols—Level II

AUGMENT OPTIONSRandomized

COGN = 204

CIT + BUSN = 354

CIT + COGN = 224

BUP-SRN = 287

VEN-XRN = 287

Nonremitters treated w/ CITLevel 1:

Level 2:

BUP-SR, bupropion sustained-release; BUS, buspirone; CIT, citalopram; COG, cognitive therapy; SER: sertraline; VEN-XR, venlafaxine extended-releaseSTAR-D III Research Design Methods.pdf. Available at: http://edc.gsph.pitt.edu/stard/public/Protocol/. Accessed June 25, 2008.

Randomized to BUP-SR or VEN-XRLevel 2A:

If no satisfactory response to COG, then L2A

SERN = 287

CIT + BUP-SRN = 354

Observations Clinical presentation of patients with major depressive

disorder (MDD) in primary and specialty care is similar General medical conditions minimally affect MDD

symptoms Substance abuse minimally affects MDD symptoms Psychiatric comorbidities complicate remission MDD + substance abuse is more likely in younger males,

but not more likely by ethnicity Patients with early-onset MDD have more severe,

disabling, chronic, or recurrent conditions Patients with early-onset MDD have more comorbidities,

poorer educational achievement, and lower likelihood of marriage

1. Warden D, et al. Curr Psychiatry Rep. 2007;9:449-459. 2. Rush AJ, et al. Am J Psychiatry. 2006;163:1905-1917. 3. Trivedi MH, et al. Neuropsychopharmacology. 2007;32:2479-2489. 4. NIMH/Results for STAR*D Study. http://www.nimh.nih.gov/health/trials/practical/stard/index.shtml. Accessed April 2, 2008. 5. Rush AJ, et al. Psychiatric Annals. 2008;38:188-193.

Clinical Implications STAR*D provides new evidence to choose among

treatment decisions for patients with major depressive disorder

Maximum tolerated dose and lengthier dosing time may be needed to achieve remission– 8–14 weeks adherence to treatment, including 4 weeks at

maximum tolerated dose, was required

– If QIDS score is not reduced by 25% by week 9, participants recommended to move to the next level

– About half of the participants became symptom-free after the first 2 treatment levels

Measurement-based tools improve adherence to therapy through patient education and collaboration– Measure symptoms/side effects at each visit

1. Warden D, et al. Curr Psychiatry Rep. 2007;9:449-459. 2. Rush AJ, et al. Am J Psychiatry. 2006;163:1905-1917. 3. Trivedi MH, et al. Neuropsychopharmacology. 2007;32:2479-2489. 4. NIMH/Results for STAR*D Study. http://www.nimh.nih.gov/health/trials/practical/stard/index.shtml. Accessed April 2, 2008. 5. Rush AJ, et al. Psychiatric Annals. 2008;38:188-193.

Suggested Reading

World Health Organization. Depression. Available at: http://www.who.int/mental_health/management/depression/definition/en/. Accessed April 9, 2008.

Greenberg PA, 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.

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;32:2479-2489.

National Institute of Mental Health. Results for Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. Available at: http://www.nimh.nih.gov/health/trials/practical/stard/index.shtml. Accessed April 2, 2008.

Warden D, Rush AH, Trivedi MH, Fava M, Wisniewski SR. The STAR*D project results: a comprehensive review of findings. Curr Psychiatry Rep. 2007;9:449-459.

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.