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This study did not find convincing evidence of a clinically important benefit for mirtazapine in addition to a SSRI or SNRI antidepressant in primary care patients with treatment-resistant depression.

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David Kessler, Alison Burns, Debbie Tallon, Glyn Lewis, Stephanie MacNeill, Jeff Round, William Hollingworth, Carolyn Chew-Graham, Ian Anderson, John Campbell, Chris Dickens, Una Macleod, Simon Gilbody, Simon Davies, Tim J Peters & Nicola Wiles.

David Kessler 1,*, Alison Burns 1, Debbie Tallon 1, Glyn Lewis 2, Stephanie MacNeill 3, Jeff Round 4, William Hollingworth 4, Carolyn Chew-Graham 5, Ian Anderson 6, John Campbell 7, Chris Dickens 7, Una Macleod 8, Simon Gilbody 9, Simon Davies 10, Tim J Peters 11, Nicola Wiles 1

1 Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK
2 Mental Health Services Unit, University College London, London, UK
3 Bristol Randomised Trials Collaboration, School of Social and Community Medicine, University of Bristol, Bristol, UK
4 Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Bristol, UK
5 Research Institute for Primary Care and Health Sciences, Keele University, Keele, UK
6 Neuroscience and Psychiatry Unit, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
7 University of Exeter Medical School, Exeter, UK
8 Hull York Medical School, University of Hull, Hull, UK
9 Mental Health Research Group, University of York, York, UK
10 Centre for Addiction and Mental Health, Toronto, ON, Canada
11 School of Clinical Sciences, University of Bristol, Bristol, UK
* Corresponding author Email:

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Responses to this report

Response by Dr David Kessler on 30 January 2019 at 2:16 PM
Author response to Dr Gupta's comment
I and my co-authors are not as confident that usual practice is as uniform as the correspondent suggests. Our concern was to be as sure as we could that we were giving an adequate dose of Mirtazapine, and avoid 'under-treatment'. Participants were free to remain on the lower dose of one capsule only (15mg Mirtazapine) and many did. For information, the entry in the BNF reads, under Mirtazapine: Initially 15–30 mg daily for 2–4 weeks, dose to be taken at bedtime


Response by Dr Arun Gupta on 9 January 2019 at 1:19 PM
study protocol unrepresentative of usual cliical practice
This study does not represent the usual clinical practice. every patient on Mirtazapine received 30mg after 14 days while in usual clinical practice this will be done only if symptoms did not remit and patient was tolerating the medicine. This study protocol increased the risk of discontinuation due to side effects and masked the potential benefit of Mirtazapine. The conclusions therefore are misguiding against a very effective medicine.


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