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Real-world effect of antidepressants for depressive disorder in primary care: protocol of a population-based cohort study
  1. Franco De Crescenzo1,2,
  2. Cesar Garriga3,
  3. Anneka Tomlinson1,
  4. Carol Coupland4,
  5. Orestis Efthimiou5,
  6. Seena Fazel1,
  7. Julia Hippisley-Cox3,
  8. Andrea Cipriani1,2
  1. 1 Department of Psychiatry, University of Oxford, Oxford, Oxfordshire, UK
  2. 2 Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, Oxfordshire, UK
  3. 3 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  4. 4 Division of Primary Care, University of Nottingham, Nottingham, UK
  5. 5 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  1. Correspondence to Dr Franco De Crescenzo, Psychiatry, University of Oxford, Oxford OX1 2JD, UK; franco.decrescenzo{at}


Introduction Clinical guidelines recommend antidepressants as the first line of treatment for adults with moderate-to-severe depression. Randomised trials provide the best evidence on the comparative effectiveness of antidepressants for depression, but are limited by a short follow-up and a highly selected population. We aim to conduct a cohort study on a large database to assess acceptability, efficacy, safety and tolerability of antidepressant monotherapy in people with depressive disorder in primary care.

Methods and analysis This is a protocol for a cohort study using data from the QResearch primary care research database, which is the largest general practice research database in the UK. We will include patients registered for at least 1 year from 1 January 1998, diagnosed with a new episode of depression and on antidepressant and a comparison group not on antidepressant. The exposure of interest will be treatment with antidepressant medications. Our outcomes will be acceptability (treatment discontinuation due to any cause), efficacy (clinical response and remission); safety (adverse events (AEs) and all-cause mortality); and tolerability (dropouts due to any AE) measured at 2 months, 6 months and 1 year. For each outcome, we will estimate the absolute risks for all antidepressants, and relative effects between antidepressants using Cox’s proportion hazards models. We will calculate HRs and 99.9% CIs for each outcome of interest.

Discussion The main limitation is the observational nature of our study, while the major strengths include the large representative population contained in QResearch and the possibly high generalisability.

  • depression & mood disorders
  • adult psychiatry

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  • Contributors FDC, AC, AT and JHC conceived and designed the study. CG, CC, OE and SF contributed to the design of the project. FDC drafted the manuscript, and all authors critically revised the manuscript and approved the final version.

  • Funding AC is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005). FDC is supported by the NIHR Research Professorship to Professor Andrea Cipriani (grant RP-2017-08-ST2-006) and by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005). OE is supported by project grant no. 180083 from the Swiss National Science Foundation.

  • Disclaimer The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health.

  • Competing interests AC has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials) and Angelini Pharma. He has also organised a workshop about digital mental health sponsored by Angelini Pharma.

  • Patient consent for publication Not required.

  • Ethics approval The project has been independently reviewed by the QResearch scientific committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data sharing not applicable as no datasets generated and/or analysed for this study. There are no data in this work.