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David Baxter PhD

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Sustained-Release Bupropion or Buspirone May Augment Citalopram Response
March 23, 2006
by Laurie Barclay, MD, Medscape

Patients with depression not responding adequately to citalopram may respond to the addition of either bupropion or buspirone, with the former having certain advantages, according to the results of a randomized study reported in the March 23 issue of The New England Journal of Medicine.

"Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach," write Madhukar H. Trivedi, MD, from the University of Texas Southwestern Medical Center in Dallas, and colleagues from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study Team. "Buspirone, a partial agonist at the postsynaptic 5-hydroxytryptamine1A (5-HT1A) receptor, enhances the activity of SSRIs [selective serotonin reuptake inhibitors] through the 5-HT1A receptors. In contrast, sustained-release bupropion appears to produce antidepressant effects by blocking the reuptake of dopamine and norepinephrine. Buspirone is not viewed as an antidepressant monotherapeutic agent, whereas sustained-release bupropion is."

STAR*D enrolled adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy at a mean final dose of 55 mg/day. Participants were randomized to receive augmentation with sustained-release bupropion at a dose of up to 400 mg/day (n = 565) or buspirone at a dose of up to 60 mg/day (n = 286).

The primary outcome was remission of symptoms at the end of the study, defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17). Raters blinded to treatment assignment obtained HRSD-17 scores by telephone. Secondary outcomes were remission at the end of the study, defined as a score of less than 6 on the 16-item Quick Inventory of Depressive Symptomatology?Self-Report (QIDS-SR-16), and response, defined as a reduction in baseline QIDS-SR-16 scores of at least 50%.

The sustained-release bupropion and buspirone groups had similar rates for HRSD-17 remission (39.0% vs 32.9%), QIDS-SR-16 remission (39.0% vs 32.9%), and QIDS-SR-16 (31.8% vs 26.9%) response. Compared with buspirone, however, sustained-release bupropion was associated with a greater reduction from baseline in QIDS-SR-16 scores (25.3% vs 17.1%; P < .04), a lower QIDS-SR-16 score at the end of the study (8.0 vs 9.1; P < .02), and a lower dropout rate due to intolerance (12.5% vs 20.6%; P < .009).

"Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings," the authors write. "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."

Study limitations include lack of placebo, unblinded delivery of treatment, and inability to exclude spontaneous remission, the nonspecific effects of treatment, or the extended use of citalopram alone as the likely explanation for these findings.

"Factors to be considered when selecting augmentation treatments include efficacy, tolerability, burden of side effects, interactions among drugs, dosing convenience, adherence, and cost," the authors conclude. "These results do raise the question of whether to use augmentation agents (or other treatment combinations) as first-line treatment in an attempt to achieve greater remission rates sooner in more patients than with SSRIs alone."

See also Change in Antidepressants May Beat Depression[/ur]
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