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Efficacy and acceptability of adjunctive psychological and pharmacological interventions for treatment-resistant depression: protocol for a systematic review and network meta-analysis
  1. Muhammad Ishrat Husain1,
  2. Rebecca Strawbridge2,
  3. Ben Carter3,
  4. Brett D M Jones1,
  5. Allan Young2,
  6. Andre F Carvalho1
  1. 1General Psychiatry and Health Systems Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  2. 2Department of Psychological Medicine, King’s College London, London, UK
  3. 3Biostatistics & Health Informatics, King’s College London, London, UK
  1. Correspondence to Dr Muhammad Ishrat Husain; Ishrat.husain{at}


Introduction Major depressive disorder (MDD) is a common debilitating illness worldwide. The vast majority of patients with MDD will not achieve remission with first-line treatment and despite the availability of different treatment modalities, at least one-third of patients experience treatment-resistant depression (TRD). There continues to be a paucity of research focused on treatment options for patients with TRD thus treatment decisions are largely based on patient and clinician preference as opposed to evidence-based practice. Herein we propose a systematic review and network meta-analysis (NMA) of available pharmacological and psychological augmentation treatments for TRD, to inform evidence-based management of TRD.

Methods and analysis We plan to conduct a search of electronic databases (MEDLINE and ISIWEB) of all dates from inception for randomised controlled trials of pharmacological and psychological augmentation interventions for adults with TRD. Articles for review will be included based upon consensus from two authors. Pharmaceutical companies will be contacted for access to any unpublished data. An NMA will compare the effectiveness pharmacological adjunctive agents for TRD using preanalysis/postanalysis, assuming consistency and transitivity.

Ethics and dissemination This project does not require research ethics board approval. The dissemination plan is to present findings at international scientific meetings and publishing results in a peer-reviewed academic journal.

PROSPERO registration number CRD42019132588.

  • adult psychiatry
  • clinical pharmacology

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  • Contributors MIH contributed to the methodology and led the first draft of the protocol. RS developed the initial methodology and helped write the first draft of the protocol. BDMJ contributed to the first draft of the manuscript, is updating searches and is obtaining unpublished data from pharmaceutical companies. BC contributed to the methodology and statistical analysis plan. AY and AFC conceived the idea for this network meta-analysis and provided critical feedback on the search strategy, methodology and manuscript. All authors approved the final version of the manuscript.

  • Funding This study represents independent research partly funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.

  • Competing interests AY has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen, in the last 3 years.

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

  • Patient consent for publication Not required.

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