Antidepressants that combine serotonergic (SSRI) and noradrenergic (NaRI) actions may have greater efficacy in treating depression than SSRI monotherapy. This theory has not been tested in any trials examining augmentation of SSRIs with a NaRI.

Does augmenting SSRIs with reboxetine, a NaRI, in depressed patients unresponsive to first line treatment, result in improved antidepressant efficacy?

In a naturalistic observational study, 30 patients with moderate to severe depression (ICD-10) who failed to respond to at least 20 mg of a SSRI, were augmented with reboxetine (4 mg increased to 8 mg if tolerated). BDI-II was measured before and 6 weeks after introduction of reboxetine. Changes in BDI scores were analysed using paired t-test.

20 out of 30 patients were able to tolerate the combination of SSRI and reboxetine treatment for at least 6 weeks. There was a significant reduction in mean BDI-II scores from 36.6 at baseline to 27.2 at six weeks follow-up (t = 4.13, df = 29, p < 0.001). 13 out of 30 previously unresponsive patients showed a response (reduction in BDI score of at least 10 points) to combination treatment, with 5 patients achieving remission (BDI < 12) over the six weeks.

Reboxetine augmentation of SSRIs can be tolerated by a majority of patients and results in a significant increase in response rates. It is a treatment strategy that should be considered in patients with moderate to severe depression who fail to respond to first line treatment with an SSRI.