Clinical Question: Is buspirone (BuSpar) or bupropion SR (Wellbutrin) better for augmentation in patients with depression who do not respond to selective serotonin reuptake inhibitor therapy?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (nonblinded)

Allocation: Uncertain

Synopsis: In the Sequenced Treatment Alternatives to Relieve Depression trial, 2,876 patients with depression were given citalopram (Celexa) in an average dosage of 40 mg per day. Approximately one third of patients went into remission (i.e., had no symptoms), and approximately one half showed a response (i.e., had at least a 50 percent reduction in symptoms). Patients who did not respond (n = 1,439) were invited to enroll in the second phase of the trial.

Treatment options for patients who failed the initial course of citalopram included switching drugs out of class to bupropion SR, within class to sertraline (Zoloft), or to the dual-action agent venlafaxine XR (Effexor); switching to cognitive therapy; or augmenting by adding buspirone, bupropion SR, or cognitive therapy. Patients could opt out of certain treatment options; for example, they could limit their randomization to only augmentation options or only switching options. Twenty-one patients agreed to randomization to any of the seven treatment options.

In this study, the results of augmentation with bupropion SR in a dosage of up to 400 mg per day and buspirone in a dosage of up to 60 mg per day were compared. A total of 565 patients were randomized to the two drugs and followed up for a mean of 14 weeks. Their average age was 41 years, 58 percent were women, and 17 percent were black. Most had recurrent depression with a mean of seven previous episodes. There was no difference between groups in the rate of remission as measured by the Hamilton Rating Scale for Depression (29.7 versus 30.1 percent) and other scales. Patients were more likely to discontinue buspirone therapy because of adverse effects (20.6 versus 12.5 percent; P < .0009; number needed to harm = 12).

A major limitation of this study was the absence of a placebo control group. Given the relapsing, remitting nature of depression, it is likely that some patients would have gone into remission without augmentation. Not enough patients chose to be randomized to both switch and augmentation options to allow for comparison.

Bottom Line: Buspirone and bupropion SR added to citalopram are similarly effective for patients with depression who do not respond initially to citalopram alone. Bupropion SR is somewhat better tolerated. This study was limited by the lack of a placebo control group. (Level of Evidence: 1b)