MIR: MIRtazapine added to SSRIs for Treatment Resistant Depression in Primary Care

Study Update
The protocol for this study was reported in 2016 – see Tallon et al, Trials 2016


The study concluded in 2017. Findings were reported in the BMJ 


The conclusion of the study was that we “did not find evidence of a clinically important benefit for Mirtazipine in addition to a 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 effect treatment options is limited.”

Study Outline
Depression is common and most depressed patients are treated by their general practitioner (GP). Antidepressants are widely prescribed, but a substantial proportion of those who take them may not get better. There is little evidence to guide GPs when this happens, and many are unsure what to do when their patients do not respond to the medication. Many patients remain in a depressed state for long periods of time, despite taking antidepressant treatment.

We are always looking for other ways to help patients whose depression does not respond to initial treatment, and we thought that it might be useful to use combinations of antidepressant drugs.

The MIR trial was a randomised clinical trial, to compare the addition of mirtazapine to a placebo for patients with depression who had been taking an SSRI or SNRI for at least 6 weeks and who remained depressed. Participants were randomised to receive either mirtazapine or a placebo while continuing to take their SSRI or SNRI antidepressant as prescribed by their GP. Neither the patient, GP, nor research team knew whether the patient was taking mirtazapine or placebo. Participants were free to withdraw from the study at any time if they wished and were offered the option of unblinding after 12 weeks when the primary outcome was measured. We continued to follow up all participants for a year to allow us to see if there were medium or longer-term benefits of this combination treatment.

MIR was a multi-site trial with four centres in Bristol, Exeter, Manchester/Keele and York/Hull, led by the University of Bristol. The Principal Investigators (PIs) from the University of Exeter Medical School were Professor John Campbell and Professor Chris Dickens. MIR was funded by the National Institute for Health Research (NIHR), the Department of Health's national health research funding scheme.  A total of 480 patients were recruited across the four trial-sites. In Exeter we recruited 122 patients through 21 GP practices across Devon.

See also University of Bristol website (1)

Core Staff
Professor John Campbell, Professor of General Practice & Primary Care, UEMS - Principal Investigator
Professor Chris Dickens, Professor of Psychological Medicine, UEMS - Principal Investigator

Dr Caroline Jenkinson, UEMS - Associate Research Fellow
Mary Carter, UEMS - Associate Research Fellow
Ellie Kingsland, UEMS - Research Administrator
Wendy Cowell, UEMS - Research Administrator

Dr David Kessler, University of Bristol  – Chief Investigator
Debbie Tallon, University of Bristol – Trial Manager
Professor Carolyn Chew-Graham, Keele University - Principal Investigator
Professor Ian Anderson, University of Manchester - Principal Investigator
Professor Simon Gilbody, University of York - Principal Investigator
Professor Una Macleod, University of York (Hull) - Principal Investigator

Trial Sites:  Bristol, Exeter, Manchester/Keele and York/Hull

Study Dates: May 2013 - October 2016 (In Exeter)

Funding:  £1,868,963 National Institute for Health Research (NIHR), Department of Health

University of Exeter Medical School (Primary Care)
Smeall Building
St Luke’s Campus
Tel: 01392 722741
Fax: 01392 722825
Contact: Professor John Campbell