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Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop
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  • Published on:
    Patient Centred Approaches to the Prescribing of Anti-depressants

    I find it concerning that the authors pay no attention to the use of Shared Decision Making regarding the use of anti-depressants. Many patients have and continue to benefit from being prescribed an anti-depressant. It is important within prescribing that patients' views, experience and preferences are given due regard.

    Conflict of Interest:
    None declared.
  • Published on:
    Response to Jauhar S, et al.
    • Mark Horowitz, Clinical Research Fellow in Psychiatry Division of Psychiatry, University College London, and Research and Development Department, North East London NHS Foundation
    • Other Contributors:
      • Michael Wilcock, Pharmacist
      • Michael Pascal Hengartner, Senior Lecturer and Counsellor
      • Martin Plöderl, Clinical psychologist
      • Joanna Moncrieff, Consultant Psychiatrist and Professor of Critical and Social Psychiatry

    We appreciate the interest in our article by Jauhar and colleagues and welcome the opportunity to address a number of misleading points in their letter.  

     

    No argument they raise undermines our central points: antidepressants do not demonstrate a clinically important difference from placebo according to any suggested threshold, including that proposed by NICE, empirical correlation with clinician evaluation or other means. There is no conclusive evidence of an above-average response sub-group so far demonstrated. The evidence for relapse prevention properties is highly problematic because of confounding by withdrawal effects. Common adverse effects are well-established, a...

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    Conflict of Interest:
    Mark Horowitz: None.

    Michael Wilcock: None.

    Michael Pascal Hengartner: I receive royalties from my book “Evidence-biased Antidepressant Prescrip-tion, published by Palgrave Macmillan in December 2021

    Martin Plöderl: None.

    Joanna Moncrieff: I have received NIHR grants as Chief Investigator of the RADAR trial and as a co-applicant on the REDUCE trial. I receive royalties on five books I have authored or edited on the topic of psychiatric drugs.
  • Published on:
    Response to: Horowitz M, Wilcock M. Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop. Drug and Therapeutics Bulletin 2022;60:7-12.
    • Sameer Jauhar, Senior Clinical Lecturer in Affective Disorders and Psychosis Psychological Medicine, IoPPN, KCL
    • Other Contributors:
      • Michael Bloomfield, Principal Clinical Research Fellow and Consultant Psychiatrist
      • Andrea Cipriani, Professor of Psychiatry and NIHR Research Professor
      • Anthony Cleare, Professor of Psychiatry
      • Joseph Hayes, Principal Research Fellow and Consultant Psychiatrist
      • Fredrick Hieronymus, Postdoctoral Researcher
      • Robert Howard, Professor of Old Age Psychiatry
      • Mario F Juruena, Senior Clinical Lecturer in Translational Psychiatry
      • Stephen M Lawrie, Professor of Psychiatry
      • Sarah Markham, Patient Advisor for the BMJ DTB /Visiting Researcher King’s College London
      • Carmine Pariante, Professor of Psychiatry
      • Andreas Reif, Head of Department, Professor of Psychiatry
      • Allan H Young, Head of School, Academic Psychiatry, Director, C entre for affective disorders. Consultant Psychiatrist.
      • David Baldwin, Professor of Psychiatry

    We read with interest the opinion piece by Horowitz and Wilcock [1], which highlights ‘considerable uncertainty about the benefit of antidepressant use in the short- and long-term’ and ‘the uncertain balance of benefits and harms’ with antidepressants, within its key learning points. We wish to counter these and address other assertions within their narrative review.

    In the section ‘Questions relating to efficacy’, the authors mention meta-analyses with newer generation antidepressants (principally the selective serotonin reuptake inhibitors [SSRIs] and serotonin-noradrenaline reuptake inhibitors [SNRIs]) which show a difference from placebo of around 2 points on the Hamilton Depression Rating Scale (HDRS), noting this does not meet thresholds of 3-, 5- or even 6-point differences, regarded by some as indicating a minimally clinically important difference.

    This is taken from data on the antidepressant mirtazapine (neither an SSRI nor SNRI) plotting change in HDRS against clinically important difference [2]. This does not have any relevance for SSRIs or SNRIs, as mirtazapine, by its effects on sleep and somatic symptoms, will exert large effects on HDRS without necessarily affecting low mood. The selection of a point on this graph was not made by authors of the original paper [3], and within-group changes from that selected study cannot be extrapolated to placebo-drug differences: a point made explicit by experts in this area [4], and by us in response to Dr H...

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    Conflict of Interest:
    Sameer Jauhar: SJ has received honoraria for educational talks given for Jannsen and Sunovian. KCL has received honoraria for educational talks he has given for Lundbeck.

    Michael Bloomfield: None.

    Andrea Cipriani: Andrea Cipriani 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); he has also received research, educational and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation and Angelini Pharma. 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.

    Anthony Cleare: In the last three years, AJC has received honoraria for educational activities from Janssen, honoraria for consulting from Allergan and Janssen, and research grant support from Protexin Probiotics International Ltd.

    Joseph Hayes: JFH is supported by the UKRI, Wellcome Trust, the University College London Hospitals NIHR Biomedical Research Centre and the NIHR North Thames Applied Research Collaboration. He has received consultancy fees from juli Health and Wellcome Trust

    Fredrick Hieronymus: None.

    Robert Howard: None.

    Mario F Juruena: MF Juruena has within the last year received honoraria for speaking from Daiichi Sankyo, Janssen, Lundbeck, Sanofi, Bionomics, EMS and Libbs; and research grant from Lundbeck and SoseiHeptares.
    MF Juruena also received the Wellcome Innovator award to study the first in-human, randomised, double-blinded, placebo-controlled study to investigate the safety and tolerability, PK and PD of oral ketamine.
    Dr Juruena’s independent research is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London Maudsley NHS Foundation Trust (SLaM), King’s College London and SLaM

    Stephen M Lawrie: None.

    Sarah Markham: None to declare.

    Carmine Pariante: Carmine Pariante is supported by: a Senior Investigator award from the National Institute for Health Research (NIHR); the NIHR Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London; the Medical Research Council; the European Commission (including the Innovative Medicine Initiative 2 Joint Undertaking (JU) under grant agreement No 853966); the NARSAD; the Psychiatry Research Trust; and the Wellcome Trust. Less than 10% of his research support in the last 10 years derives from commercial collaborations, including: a strategic award from the Wellcome Trust in partnership with Janssen, GlaxoSmithKline, Lundbeck and Pfizer; a research grant from Janssen; and consultation and speakers fees from Eli Lilly, Lundbeck, Boehringer Ingelheim, Compass, Eleusis, GH Research and Boehringer Ingelheim.

    Andreas Reif: Ad Boards and Speaker honoraria from SAGE, Biogen, Janssen, Medice and Shire/Takeda.

    Allan H Young: Employed by King’s College London; Honorary Consultant SLaM (NHS UK)
    Deputy Editor, BJPsych Open
    Paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, Sage, Novartis
    Consultant to Johnson & Johnson
    Consultant to Livanova
    Received honoraria for attending advisory boards and presenting talks at meetings organised by LivaNova.
    Principal Investigator in the Restore-Life VNS registry study funded by LivaNova.
    Principal Investigator on ESKETINTRD3004: “An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression.”
    Principal Investigator on “The Effects of Psilocybin on Cognitive Function in Healthy Participants”
    Principal Investigator on “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)”
    UK Chief Investigator for Novartis MDD study MIJ821A12201
    Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). Janssen (UK)
    No shareholdings in pharmaceutical companies.

    David Baldwin: Medical Patron of Anxiety UK (current). Clinical Advisor to National Clinical Audit of Anxiety and Depression (2017-2020). Payment from Wiley for editorship of Human Psychopharmacology journal. Provision of advice (unpaid) to Idorsia pharmaceutical company (July 2020). President-Elect of British Association for Psychopharmacology.