Treatment-resistant Depression: Does Anxiety Moderate the Efficacy of Mirtazapine?

Sarfaroj Khan 


November 11, 2020


  • The addition of mirtazapine to a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor was more effective in treating generalised anxiety in patients with treatment-resistant depression (TRD) and severe anxiety symptoms.

  • Mirtazapine may also be more effective in treating depressive symptoms and improving social functioning in those with higher levels of anxiety.

  • Conversely, there appears to be little clinical utility in adding mirtazapine in patients with TRD and without any concurrent anxiety.

Why this matters

  • Findings warrant further research to assess the benefits of mirtazapine in treating TRD with severe symptoms of generalised anxiety.

Study design

  • A secondary analysis of MIR trial including 480 patients with TRD.

  • All patients were stratified into 3 groups based on generalized anxiety disorder score (GAD-7): mild (GAD-7, ≤10), moderate (GAD-7, 11-15) and severe (GAD-7, ≥16).

  • The effect of baseline anxiety on the response of patients to mirtazapine was measured using 12-week GAD-7 and Beck Depression Inventory II (BDI-II) scores.

  • Funding: None disclosed.

Key results

  • At 12 weeks, baseline generalised anxiety moderated the efficacy of mirtazapine as measured by GAD-7 (P=.041) and BDI-II (P=.088).

  • Patients with severe generalised anxiety receiving mirtazapine vs placebo had:

    • lower GAD-7 score (adjusted difference between means [ADM], 2.82, 95% CI, −0.69 to −4.95); and

    • larger reductions in BDI-II score (ADM, −6.36; 95% CI, −1.60 to −10.84).

  • In patients with no/mild generalised anxiety, no anxiolytic (ADM, 0.28; 95% CI, −1.05 to 1.60) or antidepressant benefit (ADM, −0.17; 95% CI, −3.02 to 2.68) was seen with mirtazapine vs placebo.


  • Post hoc analysis.


Rifkin-Zybutz R, MacNeill S, Davies SJ, Dickens C, Campbell J, Anderson IM, Chew-Graham CA, Peters TJ, Lewis G, Wiles N, Kessler D. Does anxiety moderate the effectiveness of mirtazapine in patients with treatment-resistant depression? A secondary analysis of the MIR trial. J Psychopharmacol. 2020 Nov 4 [Epub ahead of print]:269881120965939. doi: 10.1177/0269881120965939. PMID: 33143538 View full text

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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