TY - JOUR
T1 - STAR*D
T2 - Revising conventional wisdom
AU - Rush, John A.
AU - Warden, Diane
AU - Wisniewski, Stephen R.
AU - Fava, Maurizio
AU - Trivedi, Madhukar H.
AU - Gaynes, Bradley N.
AU - Nierenberg, Andrew A.
N1 - Funding Information:
Bradley N. Gaynes, M.D., MPH has received grants and research support from NIMH, Agency for Healthcare Research and Quality, Robert Wood Johnson Foundation, the M-3 Corporation, Bristol-Myers Squibb Company, Novartis, Pfizer, Inc. and Ovation Pharmaceuticals. He has performed as an advisor or consultant for Pfizer, Inc., Shire Pharmaceuticals and Wyeth-Ayerst. He has also received a speaker’s honorarium from GlaxoSmithKline and provided expert testimony for Philips Lyttle, LLP.
Funding Information:
In the last 3 years, Andrew A. Nierenberg, M.D. has received research support from Cederroth, Cyberonics, Forest Pharmaceuticals, Eli Lilly & Company, Forest Pharmaceuticals, Medtronics, NARSAD, NIMH, the Stanley Foundation through the Broad Institute, Ortho-McNeil-Janssen, Pfizer Inc., Pam Labs and Shire. Past research support includes Bristol Myers Squibb, Cederroth, Forest Pharmaceuticals, Eli Lilly and Company, GlaxoSmithKline, Janssen, Lictwer Pharma, Pfizer Pharmaceuticals and Wyeth Ayerst. He received honoraria from the MGH Psychiatry Academy (MGHPA activities are supported through Independent Medical Education [IME] grants from the following pharmaceutical companies in 2008: AstraZeneca, Eli Lilly and Janssen Pharmaceuticals), MBL Publishing and Physicians Postgraduate Press. No other speaker bureaus for the past 3 years. Past speaker bureaus include Bristol-Myers Squibb, Cyberonics, Forest Pharmaceuticals, Eli Lilly and Company, GlaxoSmithKline and Wyeth Ayerst. He has provided advisory/consulting services to Abbott Laboratories, Appliance Computing Inc., Brain Cells Inc., Bristol-Myers Squibb, EpiQ, Pam Labs, PGx Health, Forest Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Janssen Pharmaceutica, Jazz Pharmaceuticals, Merck, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Sepracor, Schering-Plough, Shire, Somerset, Takeda and Targacept. Royalties have been received from Cambridge University Press and Belvoir Publishing. He holds equity in Appliance Computing Inc. He owns copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI).
Funding Information:
This project was funded by the National Institute of Mental Health under Contract N01MH90003 to UT South-western Medical Center at Dallas (P.I.: A.J. Rush). The content of this article does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.
PY - 2009
Y1 - 2009
N2 - The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequenced, randomized treatment trials following a first and, if needed, subsequent treatment steps to define the tolerability and effectiveness of various options in both acute and longer term treatment. Adult outpatients (n=4041) with nonpsychotic major depressive disorder, substantial chronic and recurrent depression, and co-morbid psychiatric and general medical conditions were enrolled in 41 representative primary and specialty care settings. About one-third of participants remitted in first step treatment with citalopram, 50% of these within 6 weeks. Poorer outcomes were associated with minority status, socioeconomic disadvantage, more axis I and III co-morbid disorders, lower function and quality of life, and anxious and melancholic features. In step 2 medication switch, there were no significant differences in remission among within-class, out-of-class or dual-action agents: sertraline (27%), bupropion-sustained release (26%) and venlafaxine-extended release (25%). In step 2 medication augmentation of citalopram, there was no significant difference in remission between bupropion-sustained release (39%) and buspirone (33%), although participants using bupropion-sustained release had greater symptom reduction and better tolerability. There were no significant differences in remission in step 2 between cognitive therapy and medication treatment in either the switch (31% vs 27%) or augmentation (31% vs 33%) strategies, although participants in cognitive therapy augmentation had a longer time to remission than those in medication augmentation (55 vs 40 days). In step 3, there were no differences in remission between a switch to mirtazapine (8%) or nortriptyline (12%), or between augmentation with lithium (13%) or T3 (triiodothyronine, liothyronine) [25%], although more participants discontinued lithium due to adverse effects than discontinued T3. In the fourth step, there was no difference in remission between tranylcypromine (14%) or venlafaxine-extended release plus mirtazapine (16%), although the combination treatment had fewer adverse effects and had the advantages of not requiring a washout period or diet restrictions. Participants requiring more than two well delivered treatments may be characterized as treatment resistant given the substantially lower remission rates after that point. Treatment resistance was associated with more concurrent axis I or III co-morbid conditions, socioeconomic disadvantage, chronicity and melancholic or anxious features. However, if participants remained in treatment for up to four steps, about 67% reached remission. Times to remission were not substantially longer for later treatment steps. The importance of reaching remission is highlighted by the lower relapse rates in naturalistic follow-up for participants entering in remission compared with those entering with response but not remission (step 1: 34% vs 59%; step 2: 47% vs 68%; step 3: 42% vs 76%; step 4: 50% vs 83%). Clinical decision making based on the itemized measurement of symptoms and adverse effects at each treatment visit was feasible in STAR*Ds real world settings and resulted in adequate dosages and durations of treatment that generally exceeded those typically found in practice settings. Although switch and augmentation strategies could not be directly compared due to the equipoise stratified randomized design, the higher remission rates at step 2 with medication augmentation are intriguing and merit further study.
AB - The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequenced, randomized treatment trials following a first and, if needed, subsequent treatment steps to define the tolerability and effectiveness of various options in both acute and longer term treatment. Adult outpatients (n=4041) with nonpsychotic major depressive disorder, substantial chronic and recurrent depression, and co-morbid psychiatric and general medical conditions were enrolled in 41 representative primary and specialty care settings. About one-third of participants remitted in first step treatment with citalopram, 50% of these within 6 weeks. Poorer outcomes were associated with minority status, socioeconomic disadvantage, more axis I and III co-morbid disorders, lower function and quality of life, and anxious and melancholic features. In step 2 medication switch, there were no significant differences in remission among within-class, out-of-class or dual-action agents: sertraline (27%), bupropion-sustained release (26%) and venlafaxine-extended release (25%). In step 2 medication augmentation of citalopram, there was no significant difference in remission between bupropion-sustained release (39%) and buspirone (33%), although participants using bupropion-sustained release had greater symptom reduction and better tolerability. There were no significant differences in remission in step 2 between cognitive therapy and medication treatment in either the switch (31% vs 27%) or augmentation (31% vs 33%) strategies, although participants in cognitive therapy augmentation had a longer time to remission than those in medication augmentation (55 vs 40 days). In step 3, there were no differences in remission between a switch to mirtazapine (8%) or nortriptyline (12%), or between augmentation with lithium (13%) or T3 (triiodothyronine, liothyronine) [25%], although more participants discontinued lithium due to adverse effects than discontinued T3. In the fourth step, there was no difference in remission between tranylcypromine (14%) or venlafaxine-extended release plus mirtazapine (16%), although the combination treatment had fewer adverse effects and had the advantages of not requiring a washout period or diet restrictions. Participants requiring more than two well delivered treatments may be characterized as treatment resistant given the substantially lower remission rates after that point. Treatment resistance was associated with more concurrent axis I or III co-morbid conditions, socioeconomic disadvantage, chronicity and melancholic or anxious features. However, if participants remained in treatment for up to four steps, about 67% reached remission. Times to remission were not substantially longer for later treatment steps. The importance of reaching remission is highlighted by the lower relapse rates in naturalistic follow-up for participants entering in remission compared with those entering with response but not remission (step 1: 34% vs 59%; step 2: 47% vs 68%; step 3: 42% vs 76%; step 4: 50% vs 83%). Clinical decision making based on the itemized measurement of symptoms and adverse effects at each treatment visit was feasible in STAR*Ds real world settings and resulted in adequate dosages and durations of treatment that generally exceeded those typically found in practice settings. Although switch and augmentation strategies could not be directly compared due to the equipoise stratified randomized design, the higher remission rates at step 2 with medication augmentation are intriguing and merit further study.
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U2 - 10.2165/00023210-200923080-00001
DO - 10.2165/00023210-200923080-00001
M3 - Review article
C2 - 19594193
AN - SCOPUS:67650499781
SN - 1172-7047
VL - 23
SP - 627
EP - 647
JO - CNS Drugs
JF - CNS Drugs
IS - 8
ER -