People who are intolerant to drugs regardless of dosage OR People who receive vigorous dosing but receive inadequate benefit (ie, do not remit). STAR*D Changed Our Working Definition of Treatment Resistance. Either is a treatment failure. 2 failed treatments = treatment resistance.
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People who receive vigorous dosing but receive inadequate benefit (ie, do not remit)STAR*D Changed Our Working Definition of Treatment Resistance
Either is a treatment failure.
2 failed treatments = treatment resistance
Rush AJ, et al. Am J Psychiatry. 2006;163:1905-1917.
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 efficacySTAR*D Level 2 Overview
Rush AJ, et al. N Engl J Med. 2006;54:1231-1242.
(To the nearest %)
Level 11 (3671) 37
Level 21,2 (1439) 31
Level 33 (377) 14
Level 44 (109) 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.
L2 therapy + lithium
N = 69
L2 therapy + T3
N = 73
N = 114
N = 121STAR*D Defining Evidence for Protocols—Level 3
Nonremitting or intolerant tofirst 2 prescribed medications
Level 3 options:
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.
Nonremitting or intolerant to any Level 3 therapy
Level 4 options:
N = 58
N = 51
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 (CT) is both an acceptable switch and an acceptable augmentation option in the 2nd step1
Benefit of CT as augmentation was slower (up to3 weeks) compared with augmenting with medication2
If time to response is of the essence, then CT may not be the best option2
Whether CT responders/remitters fare better in follow-up is to be analyzed2
CT was not as popular as expected (26% chose it), which limited these results’ statistical power1Cognitive Therapy
1. Wisniewski SR, et al. Am J Psychiatry. 2007;164:753-760. 2. Thase ME, et al. Am J Psychiatry. 2007;164:739-752.
1/3 of mothers with major depressive disorder had children with psychiatric symptoms1
The children’s symptoms eased when maternal depression remitted or at least responded (a 50% drop in symptoms)1
If the mother remained depressed, 17% of symptom-free children started manifesting Axis I symptoms1
As the mother improved, so did the child—measurably for 6 months; tapering after that2
Children of late-remitting mothers showed same improvements2STAR*D-Child Study
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.
The less likely patients are to respond to step 1 and step 2 treatments
As anxiety symptoms with depression increase
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.
Black race with psychiatric symptoms
Higher perceived functioning
Greater side effect burden
More Axis 1 comorbiditiesOverall Predictors of Attrition
Later attrition if …
Immediate attrition if …
Lower attrition if …
Warden D, et al. Am J Psychiatry. 2007;164:1189-1197.
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 took1,2,6Takeaway Messages from Levels 2–4
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.