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  • RACE AND RACISM IN PRIMARY CARE
Research

Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care

Rhona Eveleigh, Esther Muskens, Peter Lucassen, Peter Verhaak, Jan Spijker, Chris van Weel, Richard Oude Voshaar and Anne Speckens
BJGP Open 2018; 1 (4): bjgpopen17X101265. DOI: https://doi.org/10.3399/bjgpopen17X101265
Rhona Eveleigh
1 Nursing Home Physician, Department of Primary and Community Care, Radboud University Medical Center, , The Netherlands
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Esther Muskens
2 Psychologist, Department of Primary and Community Care, Radboud University Medical Center, , The Netherlands
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Peter Lucassen
3 GP, Senior Researcher, Department of Primary and Community Care, Radboud University Medical Center, , The Netherlands
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  • For correspondence: Peter.Lucassen@radboudumc.nl
Peter Verhaak
4 Professor of Primary Care, Department of Primary Care, University Groningen, University Medical Center Groningen, , The Netherlands
5 Professor of Primary Care, Department of Mental Health, Netherlands Institute for Health Service Research (NIVEL), , The Netherlands
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Jan Spijker
6 Professor of Psychiatry, Center of Depression Expertise, Pro Persona, , The Netherlands
7 Professor of Psychiatry, Behavioural Science Institute, Radboud University Nijmegen, , The Netherlands
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Chris van Weel
8 Emeritus Professor of Primary Care, Department Health Services Research and Policy, Australian National University, , Australia
9 Emeritus Professor of Primary Care, Department of Primary and Community Care, Radboud University Medical Center, , The Netherlands
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Richard Oude Voshaar
10 Professor of Psychiatry, Department of Psychiatry, Radboud University Nijmegen Medical Center, , The Netherlands
11 Professor of Psychiatry, University Medical Center Groningen, University Center for Psychiatry & Interdisciplinary Center for Psychopathology of Emotion Regulation (ICPE), University of Groningen, , The Netherlands
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Anne Speckens
12 Professor of Psychiatry, Department of Psychiatry, Radboud University Nijmegen Medical Center, , The Netherlands
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  • RE: iatrogenic harm resulting from antidepressant consumption and withdrawal
    Peter Lucassen
    Published on: 22 January 2018
  • RE: Iatrogenic harm resulting from antidepressant consumption and withdrawal
    Fiona H French
    Published on: 01 January 2018
  • Withdrawal of unnecessary antidepressant medication
    Peter Lucassen
    Published on: 19 December 2017
  • Withdrawal of Unnecessary Antidepressant Medication - Current Prospects and Future Directions
    Daniel J Dunleavy
    Published on: 13 December 2017
  • RE: withdrawal off ADs
    Peter Lucassen
    Published on: 28 November 2017
  • Withdrawal off ADs
    Mark S Carter
    Published on: 26 November 2017
  • RE: Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care
    Peter Lucassen
    Published on: 22 November 2017
  • Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care
    James F Moore
    Published on: 19 November 2017
  • Withdrawal of unnecessary antidepressant medication
    Fiona H French
    Published on: 19 November 2017
  • Published on: (22 January 2018)
    RE: iatrogenic harm resulting from antidepressant consumption and withdrawal
    • Peter Lucassen, general practitioner, senior researcher, Department of Primary and Community Care Radboud University Nijmegen, the Netherlands

    Thank you for your comments, Fiona French. And again, we agree with you.

    With hindsight we regret not having involved patients in the development of our RCT. What we need is: less prescriptions of antidepressants and more opportunities for already very busy general practitioners to refer patients to a nearby mental health professional without a long waiting list. We think that the government has an important role here.

    Competing Interests: None declared.
  • Published on: (1 January 2018)
    RE: Iatrogenic harm resulting from antidepressant consumption and withdrawal
    • Fiona H French, Retired, Member of online community for prescribed drug dependence and withdrawal

    It is extremely heartening to read the letters from Daniel Dunleavy and Peter Lucassen. Daniel Dunleavy clearly has a very good understanding of the issues involved here and the need for fractured relationships to be repaired between the prescribed dependent community and the medical profession. There is an overwhelming sense of anger and deep sense of betrayal felt by many of us which cannot be overstated and the need for acknowledgement of the harm done to us is overwhelming. It is therefore very welcome that Peter Lucassen is wiling to discuss openly the problems with their clinical trial and the need for a new clinical trial. It is just a pity that the research team had not considered involving the online patient community from the outset. We could have saved them time and money and helped them achieve a more positive outcome.

    We would agree that patients need to be offered more access to talking therapies rather than simply being prescribed drugs. And the research into optimum tapering methods is of course very welcome. However, I am astonished that it has taken decades of antidepressant prescribing to reach this point. The situation is the same in the UK, existing tapering guidelines are not fit for purpose as they are based on studies of patients who have taken the drugs for relatively short periods.1 Many patients find themselves seriously harmed either by consuming antidepressants and/or withdrawing from them and some seem to be irreversibl...

    Show More

    It is extremely heartening to read the letters from Daniel Dunleavy and Peter Lucassen. Daniel Dunleavy clearly has a very good understanding of the issues involved here and the need for fractured relationships to be repaired between the prescribed dependent community and the medical profession. There is an overwhelming sense of anger and deep sense of betrayal felt by many of us which cannot be overstated and the need for acknowledgement of the harm done to us is overwhelming. It is therefore very welcome that Peter Lucassen is wiling to discuss openly the problems with their clinical trial and the need for a new clinical trial. It is just a pity that the research team had not considered involving the online patient community from the outset. We could have saved them time and money and helped them achieve a more positive outcome.

    We would agree that patients need to be offered more access to talking therapies rather than simply being prescribed drugs. And the research into optimum tapering methods is of course very welcome. However, I am astonished that it has taken decades of antidepressant prescribing to reach this point. The situation is the same in the UK, existing tapering guidelines are not fit for purpose as they are based on studies of patients who have taken the drugs for relatively short periods.1 Many patients find themselves seriously harmed either by consuming antidepressants and/or withdrawing from them and some seem to be irreversibly damaged to the extent they can no longer function normally. It seems there is little understanding of this type of damage in the medical community. Surely it is imperative that such extreme levels of harm are openly acknowledged for what they are and research needs to be conducted into the nature of this harm and the possibilities for reversing it.

    References
    1. National Institute for Health and Care Excellence. Depression in adults: recognition and management: 1.9 Continuation and relapse prevention. Clinical guideline [CG90] https://www.nice.org.uk/guidance/cg90/chapter/1-Guidance#continuation-and-relapse-prevention (accessed 19 Jan 2018)

    Show Less
    Competing Interests: None declared.
  • Published on: (19 December 2017)
    Withdrawal of unnecessary antidepressant medication
    • Peter Lucassen, General Practitioner, Senior Researcher, Department of Primary and Community Care Radboud University Nijmegen Medical Centre, the Netherlands

    Thank you, Daniel Dunleavy, for your letter. We fully agree with you.

    The first thing we should do in primary care is reduce new antidepressant prescriptions. However, GPs should have an alternative for medication. This is the more important when GPs are prescribing less medication. GPs should talk with patients about the circumstances in their patients' lifes that have caused depression or depressed feelings. And if general practitioners do not have sufficient skills to do so, they should have the opportunity to refer patients within primary care. In the Netherlands we have had good results with mental health nurses. The government has provided the financial means to contract mental health nurses in primary care in an attempt to reduce the enormous numbers of patients who are treated in secondary care. And this works quite well. The second thing we have to do is of course trying to withdraw antidepressant medication in patients who want to do this. This is a difficult process and the best way to withdraw is not yet known, but I agree with Daniel Dunleavy that we should work together with patients, both during consultations and in research. We are currently working on this.

    Competing Interests: None declared.
  • Published on: (13 December 2017)
    Withdrawal of Unnecessary Antidepressant Medication - Current Prospects and Future Directions
    • Daniel J Dunleavy, PhD candidate, Social Work, Florida State University, College of Social Work

    The study by Eveleigh et al1 provides an important contribution to the literature on psychiatric drug withdrawal and highlights the difficulties of coming off antidepressants. Psychiatric drugs of all classes (i.e. antidepressants, neuroleptics, benzodiazepines, etc.) can cause physical and psychological withdrawal effects.2–5 Approaches for their discontinuation require further study.6

    As noted in previous letters (and subsequent responses from the authors), the rate of withdrawal can impact patient outcomes. We know that rapid discontinuation can cause intense physical and emotional discomfort,7 which may explain the low success rate in the study’s intervention group.1 Unfortunately, despite the enormous financial investment in drug research, there is a dearth of empirical evidence, from both a short- and long-term standpoint, about how different withdrawal schedules and dose reductions compare.1,5,8,9 Researchers, physicians, and patients will have to work together to disentangle the risks and benefits of various protocols and how they differ across condition (i.e. purely psychiatric conditions vs. purely medical conditions vs. mixed presentations), drug-class (i.e. SSRIs vs. TCAs vs. SGAs, etc.), and demographic groups (e.g. women vs. men; young vs. old), among other factors.

    This collaboration will have to begin with professional acknowledgement of the iatrogenic harms caused b...

    Show More

    The study by Eveleigh et al1 provides an important contribution to the literature on psychiatric drug withdrawal and highlights the difficulties of coming off antidepressants. Psychiatric drugs of all classes (i.e. antidepressants, neuroleptics, benzodiazepines, etc.) can cause physical and psychological withdrawal effects.2–5 Approaches for their discontinuation require further study.6

    As noted in previous letters (and subsequent responses from the authors), the rate of withdrawal can impact patient outcomes. We know that rapid discontinuation can cause intense physical and emotional discomfort,7 which may explain the low success rate in the study’s intervention group.1 Unfortunately, despite the enormous financial investment in drug research, there is a dearth of empirical evidence, from both a short- and long-term standpoint, about how different withdrawal schedules and dose reductions compare.1,5,8,9 Researchers, physicians, and patients will have to work together to disentangle the risks and benefits of various protocols and how they differ across condition (i.e. purely psychiatric conditions vs. purely medical conditions vs. mixed presentations), drug-class (i.e. SSRIs vs. TCAs vs. SGAs, etc.), and demographic groups (e.g. women vs. men; young vs. old), among other factors.

    This collaboration will have to begin with professional acknowledgement of the iatrogenic harms caused by these substances, whether intentional or not. Overtreatment, coercive treatment, and lack of informed consent have left many patients feeling betrayed or alienated by the medical system; in part leading to the development of patient-driven support groups and withdrawal initiatives.9–11 Professional trust must be repaired and strengthened, to increase the chances of withdrawal success. Likewise, patients and physicians will have to reconcile their beliefs about the nature and treatment of conditions like depression,12 which can cause apprehension (in either party) at the notion of discontinuing treatment. Eveleigh et al1 have provided one step toward achieving this goal. It is encouraging to read that their work on drug withdrawal will continue, with some of these considerations in mind.

    References
    1. Eveleigh R, Muskens E, Lucassen P et al. Withdrawal of unnecessary antidepressant medication: a randomized controlled trial in primary care. BJGP Open 2017. doi: https://doi.org/10.3399/bjgpopen17X101265
    2. Nielsen M, Hansen EH, Gøtzsche PC. Dependence and withdrawal reaction to benzodiazepines and selective serotonin reuptake inhibitors. Int J Risk Saf Med  2013; 25(3):155-68. doi: https://doi.org/10.3233/JRS-130594
    3. Fava GA, Gatti A, Belaise C, et al. Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: a systematic review. Psychother Psychosom 2015; 84(2), 72-81.
    4. Moncrieff J. Why is it so difficult to stop psychiatric drug treatment? It may be nothing to do with the original problem. Med Hypotheses, 2006; 67(3), 517-523. doi: https://doi.org/10.1016/j.mehy.2006.03.009
    5. Breggin PR, Cohen D. Your drug may be your problem: How and why to stop taking psychiatric medications. Cambridge, MA: De Capo Press, 1999.
    6. Ostrow L, Jessell L, Hurd M, et al. Discontinuing psychiatric medications: a survey of long-term users. Psychiatr Serv, 2017; 68(12), 1-7.
    7. Baldessarini RJ, Tondo L, Ghiani C, et al. (2010). Illness risk following rapid versus gradual discontinuation of antidepressants. Am J Psychiatry, 167(8), 934-941. doi: https://doi.org/10.1176/appi.ajp.2010.09060880
    8. Glenmullen J. The antidepressant solution: a step-by-step guide to safely overcoming antidepressant withdrawal, dependence, and “addiction”. New York, NY: Free Press, 2005.
    9. AGIDD-SMQ. Taking back control: My self-management guide to psychiatric medication. Montreal, QC: Association des groupes d'intervention en défense des droits en santé mentale du Québec, 2003.
    10. Hall W, The Icarus Project and Freedom Center. Harm reduction guide to coming off psychiatric drugs (2nd edition). http://www.willhall.net/files/ComingOffPsychDrugsHarmReductGuide2Edonline.pdf (accessed 15 Dec 2017).
    11. Moore J. Letter to Secretary of State for Health, Jeremy Hunt. https://www.change.org/p/provide-tapering-strips-to-help-users-who-want-to-stop-taking-anxiety-depression-drugs (accessed 15 Dec 2017)
    12. Cohen D, Hughes S. How do people taking psychiatric medications explain their “chemical imbalance”? Ethical Hum Psychol Psychiatry, 2011; 13(3), 176-189.

    Show Less
    Competing Interests: None declared.
  • Published on: (28 November 2017)
    RE: withdrawal off ADs
    • Peter Lucassen, General Practitioner, Senior Researcher, Department of Primary and Community Care Radboud University Nijmegen Medical Center, the Netherlands

    We agree very much with Mark Carter, that withdrawal of antidepressants is very difficult and may provoke very serious and long-lasting symptoms. When we developed the research proposal, the Dutch guidelines for depression advised the taper method we used in the trial. At the time there was hardly any scientific evidence on how to taper antidepressants. It took us several years to get this paper published and we understand that people are astonished about the taper method, because currently we know that tapering has to be much slower. In line with this, we are performing a new RCT with a very slow tapering scheme, a scheme that is different for each antidepressant and deals with its specific pharmacological properties. In this trial we allow patients to taper even slower than the scheme prescribes. In our current trial, we pay lot more attention to the symptoms patients experience during withdrawal. Moreover, in preparation of the withdrawal we discuss with patients the difficulties they expect, their experiences with earlier attempts to withdraw and we give ample information about the whole process. In the period of withdrawal we offer patients regular follow-up adjusted to their need. Thus, we hope to diminish the serious trouble patients experience during withdrawal.

    Competing Interests: None declared.
  • Published on: (26 November 2017)
    Withdrawal off ADs
    • Mark S Carter, recovering SSRI addict, concerned citizen from New Zealand.

    Being a recovering Paxil addict I was horrified when I saw the taper method used in this study. It is truly, in my opinion, totally dangerous in its ignorance and verging on criminal. Many people are tapering over many years to get off not tapering over months. The taper method should be 5-10% of the previous dose per month, and the next cut is made if and only if stable. This means that a person on 20mg Paxil may need to taper for over three years to get off. For many who have been on for more than 2 years this is their only chance of getting drug free.

    To go any faster than this will trigger full blown SSRI withdrawal... that's right withdrawal, and it is brutal and I might add due to the drug not the person. Please don't put any more lives at risk with your kamikaze, ignorant taper methods. Finally thank you for looking into helping people get out from under the weight of these horrific chemicals.

    I'm now 7 years drug free and still recovering from this poison. It’s left me sexually ruined and I would like to tell you that the first 5 years were hell. I would not wish an uninformed taper on anyone.

    Competing Interests: None declared.
  • Published on: (22 November 2017)
    RE: Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care
    • Peter Lucassen, General Practitioner, Senior Researcher, Department of Primary and Community Care Radboud University Nijmegen Medical Center, the Netherlands

    We agree with the comments by Fiona French and James Moore. At the time of developing and performing the trial, the Dutch guideline on depression advised to withdraw antidepressants by halving the dose every 2 weeks. There was no good evidence available at the time. Currently, we are running another trial on withdrawal of antidepressant medication with very slow reduction of the dose, acknowledging the fact mentioned in both comments that withdrawal is very difficult.

    Competing Interests: None declared.
  • Published on: (19 November 2017)
    Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care
    • James F Moore, Campaigner, None

    This is an important study and highlights the difficulties that many people face when trying to withdraw from their antidepressant drugs. The fact that only 6% could withdraw successfully is concerning and doctors should more actively manage medication burdens to lower the number of multi-year users. However, your tapering protocols are very fast, with users undergoing large reductions every 2 weeks. For the large community of those withdrawing that self support, a more common dosage reduction is no more than 10% per 4 weeks. I believe that the large dosage reductions required in this study are the primary reason for such a low success rate. Withdrawal effects can be minimised with a slower approach to tapering.

    Competing Interests: None declared.
  • Published on: (19 November 2017)
    Withdrawal of unnecessary antidepressant medication
    • Fiona H French, Retired, Member of online community for prescribed drug dependence and withdrawal

    I have read with interest the research by Eveleigh and colleagues. It is extremely worrying that so many patients felt unable to take the step of reducing their antidepressants and that so few were actually successful in doing so. As a member of the online support community for prescribed drug dependence and withdrawal, these findings are perhaps not surprising. The reason that so many patients congregate online is because they are unable to find appropriate information, help or support from their prescribing doctors.

    Withdrawal can be a horrendous experience and in those circumstances, it takes a great deal of courage and tenacity to endure it. There is a whole host of different withdrawal symptoms and often prescribing doctors seem to be at a loss to understand it. For a proportion of patients, the effects can last for months or years. Others seem to be irreversibly damaged. Patients were not informed of these risks by their prescribing doctors. Patients are of course very frightened at the prospect of withdrawal. They have often been led to believe that they need these drugs and will be unable to cope without them. This creates complete psychological as well as physiological dependence. Many patients still believe that antidepressants are somehow rectifying a 'chemical imbalance'.

    Withdrawal symptoms can be mistaken for the original condition for which the drugs were prescribed and patients and doctors alike can assume this is a relapse rather th...

    Show More

    I have read with interest the research by Eveleigh and colleagues. It is extremely worrying that so many patients felt unable to take the step of reducing their antidepressants and that so few were actually successful in doing so. As a member of the online support community for prescribed drug dependence and withdrawal, these findings are perhaps not surprising. The reason that so many patients congregate online is because they are unable to find appropriate information, help or support from their prescribing doctors.

    Withdrawal can be a horrendous experience and in those circumstances, it takes a great deal of courage and tenacity to endure it. There is a whole host of different withdrawal symptoms and often prescribing doctors seem to be at a loss to understand it. For a proportion of patients, the effects can last for months or years. Others seem to be irreversibly damaged. Patients were not informed of these risks by their prescribing doctors. Patients are of course very frightened at the prospect of withdrawal. They have often been led to believe that they need these drugs and will be unable to cope without them. This creates complete psychological as well as physiological dependence. Many patients still believe that antidepressants are somehow rectifying a 'chemical imbalance'.

    Withdrawal symptoms can be mistaken for the original condition for which the drugs were prescribed and patients and doctors alike can assume this is a relapse rather than the effects of withdrawal. It is vitally important that patients are informed at the outset of the many risks that are involved in consuming these drugs and limiting their prescribing would indeed be the best way to avoid years of dependence and unknown harm. However, it is also vitally important that appropriate services are provided for those already dependent.1

    Reference

    1. BMA. BMA calls for national prescription drug helpline. https://www.bma.org.uk/news/media-centre/press-releases/2016/october/bma-calls-for-national-prescription-drug-helpline (accessed 21 Nov 2017).

    Show Less
    Competing Interests: None declared.
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Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care
Rhona Eveleigh, Esther Muskens, Peter Lucassen, Peter Verhaak, Jan Spijker, Chris van Weel, Richard Oude Voshaar, Anne Speckens
BJGP Open 2018; 1 (4): bjgpopen17X101265. DOI: 10.3399/bjgpopen17X101265

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Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care
Rhona Eveleigh, Esther Muskens, Peter Lucassen, Peter Verhaak, Jan Spijker, Chris van Weel, Richard Oude Voshaar, Anne Speckens
BJGP Open 2018; 1 (4): bjgpopen17X101265. DOI: 10.3399/bjgpopen17X101265
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  • antidepressant agents
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