Mirtazapine added to selective serotonin reuptake inhibitors for treatment-resistant depression in primary care (MIR trial): study protocol for a randomised controlled trial

摘要

BackgroundPeople with depression are usually managed in primary care and antidepressants are often the first-line treatment, but only one third of patients respond fully to a single antidepressant. This paper describes the protocol for a randomised controlled trial (MIR) to investigate the extent to which the addition of the antidepressant mirtazapine is effective in reducing the symptoms of depression compared with placebo in patients who are still depressed after they have been treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) for at least 6?weeks in primary care. Methods/DesignMIR is a two-parallel group, multi-centre, pragmatic, placebo controlled, randomised trial with allocation at the level of the individual. Eligible participants are those who: are aged 18?years or older; are currently taking an SSRI/SNRI antidepressant (for at least 6?weeks at an adequate dose); score ≥14 on the Beck Depression Inventory (BDI-II); have adhered to their medication; and meet ICD-10 criteria for depression (assessed using the Clinical Interview Schedule-Revised version).Participants who give written, informed consent, will be randomised to receive either oral mirtazapine or matched placebo, starting at 15?mg daily for 2?weeks and increasing to 30?mg daily thereafter, for up to 12?months (to be taken in addition to their usual antidepressant). Participants, their GPs, and the research team will all be blind to the allocation. The primary outcome will be depression symptoms at 12?weeks post randomisation, measured as a continuous variable using the BDI-II.Secondary outcomes (measured at 12, 24 and 52?weeks) include: response (reduction in depressive symptoms (BDI-II score) of at least 50?% compared to baseline); remission of depression symptoms (BDI-II A qualitative study will explore patients’ views and experiences of either taking two antidepressants, or an antidepressant and a placebo; and GPs’ views on prescribing a second antidepressant in this patient group. DiscussionThe MIR trial will provide evidence on the clinical and cost-effectiveness of mirtazapine as an adjunct to SSRI/SNRI antidepressants for patients in primary care who have not responded to monotherapy. Trial registrationEudraCT Number: 2012-000090-23 (Registered January 2012); ISRCTN06653773 (Registered September 2012)