Medication augmentation after the failure of SSRIs for depression.
BACKGROUND
Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach.


METHODS
We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more).


RESULTS
The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009).


CONCLUSIONS
Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. (ClinicalTrials.gov number, NCT00021528.).
Trivedi
Madhukar H
MH
Mood Disorder Program and Clinic, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9119, USA. madhukar.trivedi@utsouthwestern.edu
Fava
Maurizio
M
Wisniewski
Stephen R
SR
Thase
Michael E
ME
Quitkin
Frederick
F
Warden
Diane
D
Ritz
Louise
L
Nierenberg
Andrew A
AA
Lebowitz
Barry D
BD
Biggs
Melanie M
MM
Luther
James F
JF
Shores-Wilson
Kathy
K
Rush
A John
AJ
D000328:Adult; D016642:Bupropion / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002065:Buspirone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D012074:Remission Induction; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D016642:Bupropion; D002065:Buspirone; D015283:Citalopram; D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors