Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.
BACKGROUND
After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another.


METHODS
We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores).


RESULTS
Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events.


CONCLUSIONS
After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.).
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9086, USA. john.rush@utsouthwestern.edu
A John
AJ
Rush
Madhukar H
MH
Trivedi
Stephen R
SR
Wisniewski
Jonathan W
JW
Stewart
Andrew A
AA
Nierenberg
Michael E
ME
Thase
Louise
L
Ritz
Melanie M
MM
Biggs
Diane
D
Warden
James F
JF
Luther
Kathy
K
Shores-Wilson
George
G
Niederehe
Maurizio
M
Fava
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D016642:Bupropion / Q000009:adverse effects / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D000069470:Venlafaxine Hydrochloride