STAR*D Objectives
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Compare relative efficacy of different treatment
options
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Goal is REMISSION, not just “response”
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Less than half of patients with depression remit with a
single antidepressant
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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
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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)
Age–Mean (SD)
Female
Primary
Care
Specialty
Care
Total
N = 1560
N = 2233
N = 3793
44 (13)
38 (13)
40 (13)
65%
60%
62%
67%
21%
12%
16%
76%
14%
10%
10%
72%
17%
11%
12%
Race
% white
% African American
% other
% Hispanic
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
Specialty
Care
Total
N = 1560
N = 2233
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 1
Screened
(N = 4790)
Ineligible (163) or did not
consent (613) (n = 749)
Enrolled in Level 1
(n = 4041)
HAM-D score >14
(n = 3110)
HAM-D score <14a
(n = 607)
or HAM-D missing
(n = 324)
Failed to return
(n = 234)
Eligible for analysis
(n = 2876)
Exit
(n = 592)
a HAM-D
Follow-up
(n = 1083)
= 17-item Hamilton Depression Rating Scale.
Adapted from Trivedi MH, et al. Am J Psychiatry. 2006;163:28-40.
Level 2
(n = 1201)
STAR*D Defining Evidence
for Protocols—Level II
Level 1:
Nonremitters
treated w/ CIT
Level 2:
SER BUP-SR VEN-XR COG
N = 287 N = 287 N = 287 N = 204
CIT +
CIT + COG CIT + BUS BUP-SR
N = 224
N = 354 N = 354
SWITCH OPTIONS
Randomized
AUGMENT OPTIONS
Randomized
If no satisfactory response to COG, then L2A
Randomized to
Level 2A: BUP-SR or VEN-XR
BUP-SR, bupropion sustained-release; BUS, buspirone; CIT, citalopram; COG, cognitive therapy; SER: sertraline;
VEN-XR, venlafaxine extended-release
STAR-D III Research Design Methods.pdf. Available at: http://edc.gsph.pitt.edu/stard/public/Protocol/. Accessed June 25, 2008.
Observations
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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
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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
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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
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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
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World Health Organization. Depression. Available at:
http://www.who.int/mental_health/management/depression/definition/en/. Accessed
April 9, 2008.
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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.
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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.
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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.
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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.
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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.