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Publication - Dr Jeff Round

    Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care

    phase III randomised placebo controlled trial (MIR)


    Kessler, D, Wiles, N, MacNeill, S, Tallon, D, Peters, T, Hollingworth, W, Round, J, Burns, A, Lewis, G, Chew-Graham, C, Anderson, I, Campbell, J, Dickens, C, Macleod, U, Carter, M, Jenkinson, C & Davies, S, 2018, ‘Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR)’. BMJ, vol 363.


    To investigate the effectiveness of combining mirtazapine with
    serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin
    reuptake inhibitor (SSRI) antidepressants for treatment resistant
    depression in primary care.

    Design Two parallel group multicentre phase III randomised placebo controlled trial.

    Setting 106 general practices in four UK sites; Bristol, Exeter, Hull, and Keele/North Staffs, August 2013 to October 2015.

    480 adults aged 18 or more years who scored 14 or more on the Beck
    depression inventory, second revision, fulfilled ICD-10 (international
    classification of diseases, 10th revision) criteria for depression, and
    had used an SSRI or SNRI for at least six weeks but were still
    depressed. 241 were randomised to mirtazapine and 239 to placebo, both
    given in addition to usual SSRI or SNRI treatment. Participants were
    stratified by centre and minimised by baseline Beck depression inventory
    score, sex, and current psychological therapy. They were followed up at
    12, 24, and 52 weeks. 431 (89.8%) were included in the (primary) 12
    week follow-up.

    Main outcome measures
    Depressive symptoms at 12 weeks after randomisation, measured using the
    Beck depression inventory II score as a continuous variable. Secondary
    outcomes included measures of anxiety, quality of life, and adverse
    effects at 12, 24, and 52 weeks.

    Beck depression inventory II scores at 12 weeks were lower in the
    mirtazapine group after adjustment for baseline scores and minimisation
    or stratification variables, although the confidence interval included
    the null (mean (SD) scores at 12 weeks: 18.0 (12.3) in the mirtazapine
    group, 19.7 (12.4) in the placebo group; adjusted difference between
    means −1.83 (95% confidence interval −3.92 to 0.27); P=0.09). Adverse
    effects were more common in the mirtazapine group and were associated
    with the participants stopping the trial drug.

    This study did not find evidence of a clinically important benefit for
    mirtazapine in addition to an SSRI or SNRI over placebo in a treatment
    resistant group of primary care patients with depression. This remains
    an area of important unmet need where evidence of effective treatment
    options is limited.

    Full details in the University publications repository