Half of people who stopped long term antidepressants relapsed within a year, study finds
BMJ 2021; 374 doi: https://doi.org/10.1136/bmj.n2403 (Published 30 September 2021) Cite this as: BMJ 2021;374:n2403
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Dear Editor,
Dr. Horowitz offers a valid critique of this discontinuation trial—that is, the confounding of illness relapse with antidepressant withdrawal symptoms.
Of the four antidepressants involved in the study by Lewis and Colleagues, fluoxetine and mirtazapine carry a lower risk of withdrawal symptoms upon abrupt discontinuation than sertraline and citalopram.[1] Risk of antidepressant withdrawal is highest with the serotonin reuptake inhibitors (SRIs), and generally inversely proportional elimination half-life of the SRI.[1] Among SRIs, fluoxetine has an unusually long elimination half-life, while Mirtazapine is not an SRI and has questionable serotonergic activity.[1,2]
Lewis and colleagues may help clarify the issue with existing data by stratifying patients into two groups: (1) fluoxetine and mirtazapine and (2) sertraline and citalopram, constituting low-and-high risk groups for antidepressant withdrawal, respectively. It should be noted that in the present study fluoxetine was tapered more quickly than other antidepressants (over 4 weeks versus 8 weeks), which should increase the risk of withdrawal symptoms in these fluoxetine-treated patients. Also, the SRIs in the present study were not prescribed at equivalent doses. As compared to fluoxetine and citalopram, sertraline was prescribed at a moderate (but not minimum) therapeutic dose. Sertraline-treated patients received a 50 milligram dose prior to discontinuation, whereas citalopram-treated individuals received a subtherapeutic 10 milligram daily dose. This reduction strategy for sertraline patients may have predisposed withdrawal symptoms based on the hyperbolic relationship between dose and serotonin transporter occupancy. [3,4]
Dr. Horowitz astutely notes that the taper strategy employed in this study, for all antidepressants, is insufficiently gradual based because of taper duration and terminal drug dose prior to discontinuation. A third limitation of this taper strategy is that alternating doses for SRIs with short half-lives such as sertraline and citalopram is likely to incur inter-dose withdrawal symptoms. These withdrawal symptoms would have occurred as early as week 5 of the taper protocol when the drug was alternated with placebo. This appears to align with the apparently steep increase in illness relapse between weeks 4 to 6 of the trial. That patients may have already experienced withdrawal symptoms as early as week 5 may have resulted in withdrawal symptom improvement or resolution by week 12, potentially reducing subsequent DESS scores and risk of illness relapse thereafter.
1. Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, Krebs WB (1998) Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry 44(2):77–87
2. Gillman PK. A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status. Human Psychopharmacology: Clinical and Experimental. 2006 Mar;21(2):117-25.
3. Shapiro BB. Subtherapeutic doses of SSRI antidepressants demonstrate considerable serotonin transporter occupancy: implications for tapering SSRIs. Psychopharmacology. 2018 Sep;235(9):2779-81.
4. Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. The Lancet Psychiatry. 2019 Jun 1;6(6):538-46.
Competing interests: No competing interests
Dear Editor
It is interesting that Mark Horowitz and colleagues note that stopping antidepressants commonly causes withdrawal symptoms in about half of the patients but can be misclassified as a relapse.[1]
The same has happened with the menopausal symptoms which are being vigorously promoted for medicalisation, although the menopause is a long-evolved physiological process and not a hormone deficiency disease. Falls in previously high sex steroid levels can cause withdrawal symptoms and unmask reactions to some foods or chemicals. Women shouldn’t be surprised at what happens, especially if taking alcohol.
Also combined HRT and hormonal contraceptives disrupt brain amine levels, increasing depression and therefore suicides.[2] Testosterone HRT can increase libido but also increase hirsutism, thrombo-embolic disease, and, also cause depression by lowering amine levels.
1 Horowitz Mark A. Moncrieff J, Parkin B. Antidepressant discontinuation trial misleading as it likely mis-interprets withdrawal effects as relapse Re: Half of people who stopped long term antidepressants relapsed within a year, study finds Elisabeth Mahase. 374:doi 10.1136/bmj.n2403
2 Grant ECG, Pryse Davies J. Effect of oral contraceptives on depressive mood changes and on endometrial monoamine oxidase and phosphatases. BMJ 1968;3:777-780.
Competing interests: No competing interests
Dear Editor
Lewis and colleagues randomly assigned patients with multiple depressive episodes, stable on antidepressants, to either continue antidepressants or to stop them over 4-8 weeks.[1] The authors concluded that continuing antidepressants reduces the chance of relapse even for those patients feeling well enough to stop as 39% of patients in the maintenance arm met criteria for relapse, compared to 56% in the discontinuation arm.
This conclusion is not warranted because the authors neglected to account for the possibility of antidepressant withdrawal effects being mis-classified as relapse, a fundamental problem in discontinuation trials.[2,3] Stopping antidepressants commonly causes withdrawal symptoms, with about half of patients experiencing them.[4] This is reflected in the current study where the average number of withdrawal symptoms was more than double in the discontinued group at 12 weeks (3.1 vs 1.3 out of 15 total symptoms).[1] Even this may have been an underestimate as the modified DESS scale used did not measure severity. ‘Dizziness’, for example, may mean different things to people in the maintenance group compared to the discontinuation group (such withdrawal symptoms can be so severe they have led to people being investigated for stroke).[5]
Although antidepressants were, by design, discontinued more slowly than in previous trials, we now know that 8 weeks is still a relatively short taper in patients who had been on the drugs for more than 2 years (half the dose for one month, then halve the dose every second day for one month, before stopping). Although this approach was consistent with recommendations at the time the trial was set up, since then guidance from the Royal College of Psychiatrists[6] and draft guidance from NICE[7] recommends stopping antidepressants over “months or more.”[7] Also the final doses before stopping (one quarter the highest dose), although seemingly small, have large effects on target receptors and therefore cause large shifts in effect when reduced to zero.[8] Hence withdrawal symptoms are still likely to occur.
Antidepressant withdrawal symptoms overlap with most domains of the depression scale (rCIS-R) used to detect relapse,[9] and are therefore likely to artificially inflate relapse rates in the discontinuation group.[2] The withdrawal symptoms measured by the authors include: ‘severe nervousness or anxiety’, ‘confusion or trouble concentrating’, ‘agitation’, ‘brain fog, forgetfulness or problems with memory’, ‘trouble sleeping, insomnia’, ‘fatigue, tiredness’, ‘sudden panic or anxiety.’[9] These symptoms would also register on the scales used to detect anxiety (GAD-7), depression (PHQ-9) and relapse (rCIS-R), which include the same domains.
There are several lines of evidence that withdrawal symptoms from antidepressants were indeed mis-classified as relapse in this study. There was high correlation between mean differences at the different time points on the withdrawal scale (DESS) and mean differences on the depression scale (PHQ-9) (R2=0.97) and anxiety scale (GAD-7) (R2=0.89). The differences between the average of the groups for the DESS at weeks 12, 26, 39 and 52 were 2.2, 0.7, 0.9 and 0.1, respectively; for the GAD-7 they were 2.2, 0.8, 0.6, 0.3 and for the PHQ-9 they were 2.2, 0.8, 0.6, 0.3. Together, with the overlap of withdrawal symptoms with measures of mood and relapse, this suggests that the withdrawal symptoms may account for the increase in symptom scores and relapse rate. The reverse direction of causation would be unlikely, since withdrawal symptoms include physical symptoms that are not intrinsically related to depression, including dizziness, electric shocks and headache. Whilst it is possible that relapse and withdrawal effects could co-incide, Occam’s razor would suggest one condition causes several symptoms rather than requiring several conditions.
Withdrawal confounding of relapse is also consistent with the finding that most relapses occurred when withdrawal effects are at their peak, within 6-12 weeks of when the drugs were stopped (at week 8). Indeed, 90% of the total difference in relapse rates between the two arms of the trial (at 52 weeks) was present at 12 weeks after the drugs were stopped (although this accounts for only 27% of the total follow-up time (12/(52-8)*100%). Furthermore, patients stopping fluoxetine, associated with fewer withdrawal effects than other antidepressants, because of its long elimination half-life, relapsed about 25% less than people stopping citalopram and sertraline again suggesting withdrawal effects.
Moreover anxiety, and depression scores were the same for both groups at the end of the study (week 52). Although 44% of the discontinued group returned to their medication by this point, even with twice as many people on antidepressants in the maintenance group (89% were still on medication) there was no difference in symptom scores. This suggests that discontinuation of antidepressants did not worsen mood after the period in which withdrawal symptoms had settled (there were only small differences in DESS scores by 52 weeks).
Lastly, 71% of patients in the discontinuation group correctly guessed their allocation to placebo, possibly because of withdrawal symptoms, and the expectation that they would get worse might have contributed to their worsening.[10]
As there was no effort made to manage the potential confounding of relapse by withdrawal the current study suffers the same flaws as previous discontinuation studies and cannot provide evidence of the benefits of long-term treatment, only the difficulties of stopping it. The authors could resolve some of these concerns by analysing the correlation of withdrawal symptoms with mood scores and relapse amongst individual patients to verify if withdrawal symptoms might account for relapse. They could also re-analyse their data by excluding patients who experienced significant withdrawal symptoms (e.g. modified DESS ≥ 2) from qualifying for a diagnosis of relapse. This would provide a more robust measure of relapse, reducing the potential for the misclassification of relapse as withdrawal. They could also test whether unblinding was associated with relapse.
Uncritical interpretation of this study may lead to the erroneous conclusion that antidepressants should be continued to prevent relapse, when in reality all they may be doing is preventing withdrawal symptoms. The more accurate conclusion would be that such symptoms are temporary withdrawal symptoms that can be minimised by stopping the drug more gradually, as recognised by the authors in media interviews, although not in the published paper.
References
1 Lewis G, Marston L, Duffy L, et al. Maintenance or Discontinuation of Antidepressants in Primary Care. N Engl J Med 2021;385:1257–67. doi:10.1056/NEJMoa2106356
2 Hengartner MP, Plöderl M. Prophylactic effects or withdrawal reactions? An analysis of time-to-event data from antidepressant relapse prevention trials submitted to the FDA. Ther Adv Psychopharmacol 2021;11:20451253211032052. doi:10.1177/20451253211032051
3 Hengartner MP. How effective are antidepressants for depression over the long term? A critical review of relapse prevention trials and the issue of withdrawal confounding. Ther Adv Psychopharmacol 2020;10:2045125320921694. doi:10.1177/2045125320921694
4 Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based? Addict Behav 2019;97:111–21. doi:10.1016/j.addbeh.2018.08.027
5 Haddad P, Devarajan S, Dursun S. Antidepressant discontinuation (withdrawal) symptoms presenting as ‘stroke’. J Psychopharmacol 2001;15:139–41. doi:10.1177/026988110101500210
6 Burn W, Horowitz M, Roycroft G, et al. Stopping antidepressants. Stopping Antidepressants. 2020;:1–9.https://www.rcpsych.ac.uk/mental-health/treatments-and-wellbeing/stoppin...
7 NICE. Safe prescribing and withdrawal management of prescribed drugs associated with dependence and withdrawal. 2019.https://www.nice.org.uk/guidance/indevelopment/gid-ng10141 (accessed 6 Nov 2019).
8 Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. The Lancet Psychiatry 2019;6:538–46. doi:10.1016/S2215-0366(19)30032-X
9 Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: A randomized clinical trial. Biol Psychiatry 1998;44:77–87. doi:10.1016/S0006-3223(98)00126-7
10 Moncrieff J. Are antidepressants overrated? A review of methodological problems in antidepressant trials. J Nerv Ment Dis 2001;189:288–95.
Competing interests: MH and BP have no conflicts of interest. JM reports grants from the National Institute of Health Research, that she is co-chairperson of the Critical Psychiatry Network (an informal group of psychiatrists) and a board member of the unfunded organisation, the Council for Evidence-based Psychiatry. Both are unpaid positions.
Dear Editor
I write in support of Dr Marlowe. Perhaps too often the patients are steered towards pharmacological “treatment” and kept on drugs when psychosocial interventions should have been tried and persevered with.
Competing interests: No competing interests
Dear Editor
We thank the correspondent for their interest in our research, but suggest they are mistaken in asserting that we have no interest in antidepressant withdrawal symptoms or were unaware of the debate concerning long term antidepressant use. We refer them to our publicly available trial protocol (https://discovery.ucl.ac.uk/id/eprint/10075604/ ) and entry on the ISRCTN trial registry https://doi.org/10.1186/ISRCTN15969819, where (like the correspondent) we note increasing rates of long-term antidepressant prescription, that ‘the benefits of continuing treatment are debatable’ and proposed to measure withdrawal symptoms.
We measured withdrawal symptoms in the short, medium and longer term with a modified version of the DESS (Discontinuation Emergent Symptom Scale) measured at baseline, 6 weeks, 12 weeks, 26 weeks, 39 weeks and 52 weeks. ANTLER is therefore one of the first large “double blind” randomised controlled trial in primary care to provide evidence of withdrawal symptoms occurring over a long period after antidepressant discontinuation.
Gemma Lewis and Glyn Lewis, on behalf of the ANTLER study team
Competing interests: Glyn Lewis has received fees from Fortitude Law as an expert witness involving litigation concerning withdrawal symptoms from antidepressants
Dear Editor
This study will reassure those who wish to continue on their antidepressants and to the pharmaceutical companies that produce these drugs. However, as a jobbing GP actually treating these patients I am less reassured. For many patients who have been on anti-depressants for more than a few years a 2 month tapering period is insufficient. We have become increasingly aware that many of the symptoms these patient experience on stopping their anti-depressants are due to the drug withdrawal itself rather a return of the "illness". It also important to reflect on the study's finding that 39% of those who continued on their anti-depressants suffered relapses.
It is my experience that with a significantly longer taper (the sort of tapers we use for benzodiazepine users) together with active support many can stop the medication. I also worry that there is not enough of a concern with regard to possible permanent changes in brain chemistry, down -regulation of 5HT and beta-1 receptors as well as changes in serotonin receptor sensitivity with long-term use of these drugs. This might not be a problem over decades but we just do not know.
Depression and anxiety is a biopsychosocial illness and for many of our patients addressing the non-biological aspects although much more difficult is infinitely more rewarding. We must beware the easy option of just writing a prescription and moving on to the next patient.
Competing interests: No competing interests
Dear Editor
This study will reassure those who wish to continue on their antidepressants and to the pharmaceutical companies that produce these drugs. However, as a jobbing GP actually treating these patients I am less reassured. For many patients who have been on anti-depressants for more than a few years a 2 month tapering period is insufficient. We have become increasingly aware that many of the symptoms these patient experience on stopping their anti-depressants are due to the drug withdrawal itself rather a return of the "illness". It also important to reflect on the study's finding that 39% of those who continued on their anti-depressants suffered relapses.
It is my experience that with a significantly longer taper (the sort of tapers we use for benzodiazepine users) together with active support many can stop the medication. I also worry that there is not enough of a concern with regard to changes in brain chemistry and up-regulation of serotonin receptions with long-term use of these drugs. This might not be a problem over decades but we just do not know. Depression and anxiety is a biopsychosocial illness and for many of our patients addressing the non-biological aspects although much more difficult is infinitely more rewarding. We must beware the easy option of just writing a prescription and moving on to the next patient.
Competing interests: No competing interests
Dear Editor
The reporting (1) of the long-awaited ANTLER study (2) has raised great alarm amongst those of us who, for years, have been working to support people who wish to come off antidepressants – and have been raising awareness of the actual patient experiences of taking antidepressants ‘as prescribed’. The study itself (2) actually reinforces and confirms just what we have seen happening – to all too many people. Almost all of the references in the NEJM paper (2) are up to 2016 when the ANTLER study protocols were established, so there feels to be a complete time-warp – with the study seemingly designed to conclude that long-term antidepressants are ‘a good thing’ and omitting, even in the Discussion, the emerging evidence of issues with antidepressant withdrawal.
Our 2020 Patient Voice article (3) tracks what is happening to people – and how antidepressant withdrawal is frequently mis-diagnosed as ‘relapse’ or the onset of another medical condition.
“The experience of this sample brings to light, for the first time, the extent to which antidepressant withdrawal symptoms are mistaken for relapse, due to the widespread lack of awareness of withdrawal symptoms amongst GPs.”
Stevie Lewis has written for BJGP ‘Four research papers that I wish my GP had read before prescribing antidepressants’ (4), and Ed White has written about his own research showing that tens of thousands of patients are turning to Facebook groups for support to taper antidepressants (5).
There seems to be very little interest by those working within Primary Care to investigate this hugely important issue – or to provide prescribers with up-to-date information and guidance about how antidepressants may be more safely tapered. My own letter to BJGP journal (6) refers to updated information – which seems to be otherwise ‘not being seen’ by overwhelmed GPs.
The ‘new research’ (2) is already desperately out-of-date and will unfortunately seriously compound the problems faced by patients – most especially that of being disbelieved by their prescribers when they run into difficulties, further eroding doctor/patient relationships.
A new book, ‘Antidepressed’ by Beverley Thomson (7), is due for release shortly and offers a readable comprehensive roundup of information essential for those involved in prescribing or taking antidepressants – as well as including a number of patient experience accounts which were published for our Scottish petition (8).
(1) Mahase E. Half of people who stopped antidepressants relapsed within a year, study finds. BMJ 2021;374:n2403 Half of people who stopped long term antidepressants relapsed within a year, study finds | The BMJ
(2) Lewis G et al. Maintenance or Discontinuation of Antidepressants in Primary Care N Engl J Med 2021; 385:1257-1267 DOI: 10.1056/NEJMoa2106356 https://www.nejm.org/doi/full/10.1056/NEJMoa2106356?query=recirc_inIssue...
(3) Guy A, Brown M, Lewis S, Horowitz M. The ‘patient voice’: patients who experience antidepressant withdrawal symptoms are often dismissed, or misdiagnosed with relapse, or a new medical condition. Therapeutic Advances in Psychopharmacology. January 2020. doi:10.1177/2045125320967183 The ‘patient voice’: patients who experience antidepressant withdrawal symptoms are often dismissed, or misdiagnosed with relapse, or a new medical condition - Anne Guy, Marion Brown, Stevie Lewis, Mark Horowitz, 2020 (sagepub.com)
(4) Lewis S. Four research papers I wish my GP had read before prescribing antidepressants. British Journal of General Practice 2021; 71 (708): 316-317. DOI: https://doi.org/10.3399/bjgp21X716321 Four research papers I wish my GP had read before prescribing antidepressants | British Journal of General Practice (bjgp.org)
(5) White E. Tapering antidepressants: why do tens of thousands turn to Facebook groups for support? British Journal of General Practice 2021; 71 (708): 315. DOI: https://doi.org/10.3399/bjgp21X716309 Tapering antidepressants: why do tens of thousands turn to Facebook groups for support? | British Journal of General Practice (bjgp.org)
(6) Brown M. Letter: Four research papers … prescribing antidepressants. British Journal of General Practice 2021; 71 (710): 397. DOI: https://doi.org/10.3399/bjgp21X716837 Four research papers … prescribing antidepressants | British Journal of General Practice (bjgp.org)
(7) Thomson B. Antidepressed. 2021 ISBN 9781578269235 Antidepressed by Beverley Thomson: 9781578269235 | PenguinRandomHouse.com: Books
(8) Petition PE01651. Prescribed drug dependence and withdrawal. Scottish Parliament 2017 - 2021
PE01651: Prescribed drug dependence and withdrawal - Getting Involved : Scottish Parliament
Competing interests: No competing interests
Re: Half of people who stopped long term antidepressants relapsed within a year, study finds
Antidepressant discontinuation trial lacks consideration of evidence based psychological alternatives for continuation of antidepressants
Dear editor,
Lewis and colleagues (1) reported on the protective effect of maintenance of antidepressants versus discontinuing antidepressants for patients with depression in primary care as discussed in BMJ (BMJ 2021;374:n2403). In this RCT, the authors concluded that continuing antidepressants reduces the likelihood of relapse compared to discontinuing antidepressants over a 52-week follow-up. Patients who took part in the trial either had two previous episodes or took antidepressants for at least two years.
The study results may lead to the interpretation that long term use of antidepressant after remission of unipolar depression is the only evidence-based strategy to prevent relapse. However, the authors conclusion overlooks the robust evidence for psychological interventions as an alternative to long term use of antidepressant for relapse prevention in unipolar depression.
In the past decade there is accumulating robust evidence based on several RCT’s and meta-analyses for the effect of brief psychological interventions as relapse prevention strategy. That is, evidence shows that brief psychological interventions (i.e. Preventive Cognitive Therapy and Mindfulness Based Cognitive Therapy) are effective in reducing the risk for relapse in unipolar depression (2,3). Psychological interventions are also an alternative to antidepressants in recurrent unipolar depression. RCT’s and meta-analyses show that Preventive Cognitive Therapy (PCT) and Mindfulness Based Cognitive Therapy (MBCT) delivered during tapering and stopping antidepressants are an alternative for continuation of antidepressants, also in primary care (e.g., 3–5).
Furthermore, the latest Individual Patient Data meta-analysis on this topic demonstrated that brief psychological interventions (PCT, MBCT), delivered after remission, are an alternative for long-term use of antidepressants, also for those with high risk of relapse (3). The non-inferiority/preventative effect of psychological interventions was demonstrated for longer than one year (at least 15 months).
The evidence for alternative pharmaceutical strategies to stay well after a depression, is completely lacking in the article. However, the evidence for alternatives for medication is crucial for shared decision making with an individual that wishes to taper antidepressants in unipolar depression. These results open up the opportunity for individuals with recurrent unipolar depression that wish to taper antidepressants (as well as general practitioners and other clinicians) to choose between long term use of antidepressants or psychological interventions as alternative (that is PCT or MBCT).
prof. dr. Claudi Bockting, professor of Clinical Psychology in Psychiatry,
AmsterdamUMC/Centre for Urban Mental Health, University of Amsterdam
c.l.bockting@amsterdamumc.nl
dr. Josefien Breedvelt, research director, National Centre for Social Research & AmsterdamUMC / @JosefienUMH
1. Lewis G, Marston L, Duffy L, Freemantle N, Gilbody S, Hunter R, et al. Maintenance or Discontinuation of Antidepressants in Primary Care. N Engl J Med [Internet]. 2021 Sep 29;385(14):1257–67. Available from: https://doi.org/10.1056/NEJMoa2106356
2. Breedvelt JJF, Brouwer ME, Harrer M, Semkovska M, Ebert DD, Cuijpers P, et al. Psychological interventions as an alternative and add-on to antidepressant medication to prevent depressive relapse: systematic review and meta-analysis. Br J Psychiatry. 2020;0(1–8).
3. Breedvelt JJF, Warren FC, Segal Z, Kuyken W, Bockting CL. Continuation of Antidepressants vs Sequential Psychological Interventions to Prevent Relapse in Depression: An Individual Participant Data Meta-analysis. JAMA psychiatry. 2021 Aug;78(8):868–75.
4. Bockting CLH, Klein NS, Elgersma HJ, van Rijsbergen GD, Slofstra C, Ormel J, et al. Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised control. The Lancet Psychiatry [Internet]. 2018;0366(18):1–10. Available from: http://dx.doi.org/10.1016/S2215-0366(18)30100-7
5. Kuyken W, Hayes R, Barrett B, Byng R, Dalgleish T, Kessler D, et al. Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): A randomised controlled trial. Lancet [Internet]. 2015;386(9988):63–73. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=psyc12&NEWS=N&A...
Competing interests: CLB is president of the European Association of Clinical Psychology and Psychological Treatment (EACLIPT) and co-developer of the Dutch multidisciplinary clinical guideline for depression, for which she receives no remuneration. She is also a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this topic. CLB has presented several keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops on psychological interventions and wrote several books/co-edited books including a book on Preventive Cognitive Therapy , some of which include a fee or royalties. FB has no competing interests.