title: What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression.
abstract: The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a large-scale practical clinical trial to determine which of several treatments are the most effective "next-steps" for patients with major depressive disorder whose symptoms do not remit or who cannot tolerate an initial treatment and, if needed, ensuing treatments. Entry criteria were broadly defined and inclusive, and patients were enrolled from psychiatric and primary care clinics. All participants began on citalopram and were managed by clinic physicians, who followed an algorithm-guided acute-phase treatment through five visits over 12 weeks. At the end of each sequence, patients whose depression had not fully remitted were eligible for subsequent randomized trials in a sequence of up to three clinical trials. In general, remission rates in the study clinics were lower than expected, suggesting the need for several steps to achieve remission for most patients. There was no clear medication "winner" for patients whose depression did not remit after one or more aggressive medication trials. Both switching and augmenting appeared to be reasonable options when an initial antidepressant treatment failed, although these two strategies could not be directly compared. Further, the likelihood of remission after two vigorous medication trials substantially decreased, and remission would likely require more complicated medication regimens for which the existing evidence base is quite thin. STAR*D demonstrated that inclusion of more real-world patients in clinical trials is both feasible and informative. Policy implications of the findings, as well as the study's limitations, are discussed.
authors.affiliation: Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. bgaynes@med.unc.edu
authors.forename: Bradley N
authors.initials: BN
authors.lastname: Gaynes
authors.forename: Diane
authors.initials: D
authors.lastname: Warden
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016642:Bupropion / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use; D015928:Cognitive Behavioral Therapy; D003511:Cyclohexanols / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000628:therapy; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011324:Primidone / Q000627:therapeutic use; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D016642:Bupropion; D015283:Citalopram; D003511:Cyclohexanols; D018765:Dopamine Uptake Inhibitors; D011324:Primidone; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride