Transcript Sample Presentation Title Slide

STAR*D Changed Our Working
Definition of Treatment Resistance
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People who are intolerant to drugs regardless
of dosage
OR
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People who receive vigorous dosing but
receive inadequate benefit (ie, do not remit)
Either is a treatment failure.
2 failed treatments = treatment resistance
Rush AJ, et al. Am J Psychiatry. 2006;163:1905-1917.
STAR*D Level 2 Overview
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4 switch options and 3 augment options
If someone had a clear medication intolerance or <25% decrease
in symptom severity by week 9 on an adequate dose, then that
person was encouraged to move to the next treatment level
Overall remission rate at Level 2 was 31%
1 in 4 people who switched treatments remitted in Level 2
1 in 3 people who augmented the citalopram treatment remitted in
Level 2
It matters less which drug is chosen than how the drug is used
No advantages in switching patients in class, out of class, or
switching to a dual-action antidepressant
Substantial pharmacologic differences in classes of drugs don’t
translate into differences in efficacy
Rush AJ, et al. N Engl J Med. 2006;54:1231-1242.
Remission Rates by Levels1
By QIDS-SR16 ≤5
Level
Level 11
Level 21,2
Switch
Augment
Level 33
Switch
Augment
Level 44
(n)
Overall Remitted1
(3671)
(1439)
(789)
(650)
(377)
(235)
(142)
(109)
37
31
(To the nearest %)
14
13
QIDS-SR16 = Quick Inventory of Depressive Symptomatology, Self-Rated
1. Rush AJ, et al. Am J Psychiatry. 2006;163:1905-1917. 2. Wisnieweski SR, et al. Am J Psychiatry.
2007;164:753-760. 3. Nierenberg AA, et al. Am J Psychiatry. 2006;163:1519-1530. 4. McGrath PJ, et al. Am J
Psychiatry. 2006;163:1531-1541.
STAR*D Defining Evidence for
Protocols—Level 3
Level 3:
Nonremitting or intolerant to
first 2 prescribed medications
Level 3 options:
MRT
N = 114
NTP
N = 121
SWITCH OPTIONS
Randomized
L2 therapy
+ lithium
N = 69
L2 therapy
+ T3
N = 73
AUGMENT OPTIONS
Randomized
RESULTS: 14% remission rate overall (QIDS-SR16 <5 at exit)
Remission happened, on average, after 9.6 weeks
MRT = mirtazapine; NTP = nortriptyline; T3 = triiodothyronine.
Nierenberg AA, et al. Am J Psychiatry. 2006;163:1519-1530.
STAR*D Defining Evidence for
Protocols—Level 4
Level 4:
Nonremitting or intolerant
to any Level 3 therapy
Level 4 options:
TCP
N = 58
VEN-XR
+ MRT
N = 51
SWITCH OPTIONS
Randomized
RESULTS: 13% remission rate overall (QIDS-SR16 < 5 at exit)
TCP = tranylcypromine; VEN-XR = venlafaxine extended release; MRT = mirtazapine.
McGrath PJ, et al. Am J Psychiatry. 2006;163:1531-1541.
Cognitive Therapy
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Cognitive therapy (CT) is both an acceptable
switch and an acceptable augmentation option in the
2nd step1
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Benefit of CT as augmentation was slower (up to
3 weeks) compared with augmenting with
medication2
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If time to response is of the essence, then CT may
not be the best option2
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Whether CT responders/remitters fare better in
follow-up is to be analyzed2
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CT was not as popular as expected (26% chose it),
which limited these results’ statistical power1
1. Wisniewski SR, et al. Am J Psychiatry. 2007;164:753-760. 2. Thase ME, et al. Am J Psychiatry. 2007;164:739-752.
STAR*D-Child Study
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1/3 of mothers with major depressive disorder had
children with psychiatric symptoms1
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The children’s symptoms eased when maternal
depression remitted or at least responded (a 50%
drop in symptoms)1
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If the mother remained depressed, 17% of symptomfree children started manifesting Axis I symptoms1
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As the mother improved, so did the child—
measurably for 6 months; tapering after that2
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Children of late-remitting mothers showed same
improvements2
1. Weissman MM, et al. JAMA. 2006;295:1389-1398. 2. Pilowsky DJ, et al. Am J Psychiatry. AJP in Advance. June 16,
2008.A1A:1-12.
Ancillary Study—Anxious Depression
As anxiety
symptoms
with
depression
increase
The less likely patients
are to respond to step 1
and step 2 treatments
The more likely they
are to experience
adverse effects
The more likely they
are to have greater side
effect burden
Nelson JC. Am J Psychiatry. 2008;165:297-299.
Overall Predictors of Attrition
Later attrition if …
Immediate attrition if …
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Black race
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Black race
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Younger age
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Less education
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Higher perceived
functioning
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Greater side effect burden
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Hispanic ethnicity
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More Axis 1 comorbidities
Lower attrition if …
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>1 MDD episode
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Older age
Warden D, et al. Am J Psychiatry. 2007;164:1189-1197.
Takeaway Messages from Levels 2–4
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People with greater side effect burden prefer switching to a new
medication vs augmenting1,2,3
People most amenable to cognitive therapy have more education
and/or a family history of mood disorders3,4
People with 2 failed treatments will take longer to achieve
remission (often 10–14 weeks)1
Treatment-resistant cases will have greater treatment intolerance
and greater side effect burden5,6,7
T3 deserves consideration as an augment drug when 2 treatments
fail5
MAOI administration should be left to specialists who have
experience using this drug class7
Despite differences in presumed mechanism of action, patient
outcomes did not differ significantly according to which drug(s)
they took1,2,6
1. Rush AJ, et al. Am J Psychiatry. 2006;163:1905-1917. 2. Rush AJ, et al. N Engl J Med. 2006;54:1231-1242.
3. Wisniewski SR, et al. Am J Psychiatry. 2007;164:753-760. 4. Thase ME, et al. Am J Psychiatry. 2007;164:739-752.
5. Nierenberg AA, et al. Am J Psychiatry. 2006;163:1519-1530. 6. Rush AJ. Am J Psychiatry. 2007;164:201-204.
7. McGrath PJ, et al. Am J Psychiatry. 2006;163:1531-1541.
Suggested Readings
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Rush AJ, Trievdi NJ, 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.
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;54:1231-1242.
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.
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.
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.
Rush AJ. STAR*D: what have we learned? Am J Psychiatry. 2007;164:201-204.
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.
Warden D, Trivedi MH, Davis L, et al. Predictors of attrition during initial (citalopram) treatment for
depression: a STAR*D report. Am J Psychiatry. 2007;164:1189-1197.
Pilowsky DJ, Wickramaratne P, Tag M, et al. Children of depressed mothers 1 year after initiation of
maternal treatment: findings from the STAR*D study. Am J Psychiatry. AJP in Advance June 16,
2008:AiA1-12.
Ladsen L. STAR*D study leaders at UT Southwestern test two-drug approach to depression in new
CO-MED trial. Press release. July 22, 2008. http://www.eurekalert.org/pub_releases/2008-07/usmcssl072108.php. Accessed August 10, 2008.