Added Mirtazapine Doesn’t Help Treatment-Resistant Depression

November 15, 2018

Adding mirtazapine to a serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) for treatment-resistant depression is no more effective than adding placebo, according to a study published online in The BMJ.

“Our study has found that there is unlikely to be a clinically important benefit for mirtazapine over placebo in addition to an SSRI or SNRI antidepressant in primary care patients with treatment resistant depression and that the combination is not well tolerated,” said study lead author David Kessler, MD, of University of Bristol in the United Kingdom.

The multicenter, double-blind randomized controlled trial included 480 adults with depression treated with an SNRI or SSRI antidepressant for at least 6 weeks with no response. For an additional 12 weeks, 241 participants received added mirtazapine while 239 received added placebo.

Does Depression Severity Limit Treatment Options?

At 12 weeks, there was a small difference in favor of the mirtazapine group, researchers reported. However, the benefit was not clinically important, and researchers could not rule out the possibility of no effect. What’s more, at 24 weeks and 52 weeks, outcome data showed even smaller differences between the groups.

Adverse effects were more common in patients taking mirtazapine, according to the study, and were associated with stopping treatment.

“We recommend that general practitioners think very carefully before adding mirtazapine as a second antidepressant in this group of patients,” Dr. Kessler said. “This is particularly important when there are clear alternatives such as cognitive behavioral therapy, which has been shown to be effective in this group of patients.”

—Jolynn Tumolo


Kessler DS, MacNeill SJ, Tallon D, et al. Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR). The BMJ. 2018 October 31.

Popular drug combination for treatment resistant depression is not more effective than a single antidepressant in primary care [press release]. Bristol, United Kingdom: University of Bristol; November 1, 2018.