A reply to the Frontline article ‘Bad Medicine: bipolar II disorder’ and the responses it attracted.
This is a BMJ response written by me on the 8th June 2011. It is a consideration of mood disturbance and overmedicalisation. None of my words take away from my understanding of the suffering
that disturbances of mood may bring.
Our own window:
“We can eventually make quite a lot of sense of this habitat if we patiently put together the data from different angles. But if we insist that our own window is the only one worth looking through, we shall not get very far.” Mary Midgley[1]
John Brockman in his collection of scientific essays ‘Beyond the scientific revolution: The Third Culture’[2] made two key demands for his book, that given the stormy debate raised by the recent Frontline article ‘Bad Medicine: bipolar II disorder’ [3] need to be considered:
(1) that we need to tolerate scientific disagreement,
(2) that the role of the academic includes communicating
Nevertheless, it was not helpful for Dr Spence to state that ‘Modern psychiatry, for all its evidence, is merely an intellectual construct, neither fact nor science.’ Reality is after all chock full of constructs, and here Dr Spence forgets many strides made in mental health care, however imperfect the classification of such suffering continue to be.[4] Here, Professor Michael Rutter suggests we remember: “Progress in science—clinical science and basic science—has to come from questioning the given wisdom of the day and doing so in a style that builds constructively to a better understanding. In other words, destructive criticism is rarely the way to go”[5]
It is understandable that Academic Psychiatry responded to Dr Spence most defensively; less understandable was all-out personal attack. Hackles raised may have weakened reason and here the academic world of British psychiatry, as Dr Spence argues, continues to ignore our professional oath primum non nocere (above all do no harm). Many of the respondents to Des Spence belong to the academically distinguished cohort who in July 2008 sounded the alarm for British psychiatry to ‘wake up.’ Their call somehow managed to present an approach to suffering that – going by the correspondence – raised more concern than it did support.[6]
Rather than getting embroiled in the well-rehearsed arguments over the status of Bipolar II, I wish to focus on the underlying theme of Dr Spence’s frontline. He returns primarily to the medicalization of today (here 450 words can never be sufficient) and he has established, through a series of critiques that his concern is not confined to mental health. Readers today realise that debate on medicalization is not new, and that the view presented by Ivan Illich in 1975 that this is universally bad is an over-simplistic approach.[7] [8]
What follows in this brief paper is an examination of antidepressant prescribing and where it sits today within a world that is beyond that described by Ivan Illich. To consider such it is crucial to gather all available evidence-base, but also not to dismiss a collective narrative less quantifiable. Medicine, in its evidence-base, should accept that numbers (that which is quantifiable) and words (the qualitative) are equal forms of measurement. It is disappointing that we need reminding of this essential evidence and that the individual story is increasingly lost in pursuit of ever greater denominators.
Last year 40 million prescriptions of antidepressants were issued in England and 4.5 million in Scotland. This is, in its own right is an evidence base that Dr Spence insists must not be ignored and that Professor Ian Reid insists must not be superficially analysed.
If we divide the total number of prescriptions of antidepressants issued in England[9] (40 million) and Scotland[10] (4.5 million) last year, by an average of five prescriptions per depressed, we have a crude approximate of 9 million on regular pharmacological treatment.[11] Of course the true estimate will be considerably lower as revealed by Moore and colleagues,[12] as antidepressants are appropriately prescribed for other symptoms of life: in particular low dose Amitriptyline which is used in both sleep disorder and neuropathic pain.
In what follows, I will present 9 reasons, one per million, open of course to debate, why mankind should not simply dismiss the ‘cod philosophy’[13] of Dr Spence.
First: ‘truth.’
This small, but powerful word was used repeatedly by respondents in their opposing argument to Dr Des Spence.[14] Truth as it relates to evidence-based medicine is the subject of this edition of the British Medical Journal.
Dr Philip J Cowen, Professor of Psychopharmacology at the University of Oxford, light-heartedly questioned if Dr Des Spence was real: suggesting he might be no more than an editorial construct. Here Professor Cowen linked any ‘Big Pharma’ notion with fantastical conspiracy.[15] Yet printed in the same edition of that British Medical Journal was the alternative take on ‘truth’ as given by Ray Moynihan: “With medical science so contaminated by conflicts of interest, what evidence can we trust?”[16]
Here are some of the paid opinion leaders in UK psychiatry [I have used information available in the public domain to construct visual summaries of the competing interests of some key opinion leaders. I have done so in the spirit of the relevant guidance of the Royal College of Psychiatrists].
Professor Cowen’s response, entitled ‘Constructionism,’ mentioned one competing interest: “I am one of the authors of the “Shorter Oxford Textbook of Psychiatry” which treats bipolar II disorders as if it were a medical condition.” In May 2011 Professor Cowen wrote the lead Editorial in the British Journal of Psychiatry – ‘Has psychopharmacology got a future?’ in which he revealed more conflicts of interest than he chose to reveal in his reply to Dr Spence.[17] In this editorial Cowen described past British Medical Journal coverage on antidepressants as ‘deranged’[18] and warned today of the demise of pharmaceutical innovation. It is true that in 2011 two major pharmaceutical companies have announced cessation of research activity in the field of psychiatric drug development. However not all involved in neuro-pharmaceutics seem as concerned as Professor Cowen, and indeed some within the industry believe that declining innovation is a myth.[19] Professor Cowen entitled his response to Dr Spence’s frontline ‘constructionism’; however his editorial in the British Journal of Psychiatry[20] made no mention of unpublished evidence, which leaves him, and the editors of the British Journal of Psychiatry, open to the charge of communicating less than the whole truth. Two of the most frequently cited cases involving unpublished evidence relate to antidepressants: paroxetine and reboxetine. In the case of the latter, it was revealed recently that 74% of patient data had previously been unpublished: when this evidence was included the conclusion was rather different than that so marketed: “reboxetine is overall an ineffective and potentially harmful antidepressant”[21]
In 2008, Dr Ben Goldacre published ‘Bad Science’[22] and it has since become a bestseller. Two chapters in this book are worth considering when it comes to debate on antidepressant prescribing. The first is ‘How the media promote the public misunderstanding of science.’ We are used to journalism that reduces the horrid reality of depressive illness: for example calling medication ‘happy pills’ or sufferers ‘pill poppers.’ Yet the chapter that follows is equally important, as in it Ben Goldacre suggests reasons “why clever people believe stupid things.” In terms of evidence-based research he argues that we: ‘tend to seek out confirmatory information on any given hypothesis. ‘[23]
Dr Richard Smith, former Editor of the British Medical Journal departed office in 2003 with his own concern: In his ‘goodbye’, Dr Smith warned of confounding marketing with medical education. This is not a new phenomenon, but in our generation cannot be dismissed, despite the good that many drugs have brought to life and greater longevity. In terms of Academic Psychiatry this subject was given careful consideration by Thomas A. Ban.[25]
Second: what is health?
The central tenet of Des Spence’s argument is that too much of life is being ‘disordered’ and that this has consequences for us all. Some of the psychiatrists who responded to his frontline piece, accused him of either mind-body dualism or worse still ‘trivialising’ suffering. Anybody who has read the British Medical Journal[26], or any other journal for that matter over the last few years, cannot have failed to notice that boundaries of illness are moving: today we have pre-hypertension, cholesterolaemia, glycaemia etc.
As an old-age psychiatrist, I am obviously interested in research into Alzheimer’s pathology.[27] It appears to be emerging that this disease is not an ‘all-or-none’ entity: amyloids, neurofibrillary tangles and apoE alleles, are all now thought to be active components of normal neuroplastic processes. In other words, Alzheimer’s is not a disease (as so classically understood) but a physiological yet detrimental response to complex neuroplasticities. Ming Yi, from the Neuroscience Research Institute, Peking University, in consideration of this new understanding of Alzheimer’s pathology, suggests that we define health first, then diseases. Such a strategy will, Ming Yi so argues, reveal the ‘truth’ that most diseases appear in a dormant manner originating from a physiological continuum. Furthermore, Yi argues that this understanding not only provides a consensual framework for researchers, but should also benefit early diagnosis and intervention for patients. He goes on to suggest that such a ‘healthy’ framework might be a parallel to follow for mood disorders and their treatment.
Third: ticking all the boxes
In his reply to the frontline, Dr Ian M. Anderson, psychiatrist, questioned if we have become over-reliant on self-report measures such as questionnaires.[28] We must not forget that we are living in an age of patient empowerment. This is most welcome but depends crucially upon coherent public health education. Under the quality and outcomes framework, UK general practitioners are rewarded for using validated questionnaire measures of the severity of depression at the outset of treatment. While general practitioners are using the questionnaires in more than 90% of diagnosed cases, qualitative evidence suggests they doubt the validity of the measures and use their clinical judgment to decide about treatment regardless of patients’ questionnaire scores.[29] Professors Kendrick and Dowrick, in the only large scale study on the use of such self-report questionnaires concluded: “It should be emphasised that neither PHQ- 9 and HAD-D is an optimum measure of the severity of depression, and scores above the recommended cut-off values give only an indication that a particular patient is likely to have major depressive disorder.”
‘Incentivised care’, such as this, Chris van Weel, professor of general practice has argued is no substitute for professional judgment: “given the limited research, this is an area where general practitioners’ experience is well ahead of scientific evidence. Exploration of this experience could further improve the QOF process.”[30] In Scotland, the NHS supported campaign ‘doingwell’ launched itself upon the back of internet self-assessment by PHQ-9. Beyond Professor Van Weel, concern has been expressed more widely, including Professor Ian Reid of Aberdeen: “it maybe that QOF depression measures will simply have to be reconsidered if we wish to keep faith with the evidence base. For now, GPs should continue to exercise circumspection when interpreting depression severity measure scores.”[31]
Fourth: all that is classified.
As someone who is interested in the history of psychiatry there is one perennial conundrum that has presented itself every year since Johann Reil coined psychiatry[32]: the classification of mental suffering. Dr Spence has every right to remind us that we have not yet cracked this. Today it is necessary to follow Professor Craddock’s call for pragmatism. The search for biological markers will go on, and it is a cause that we should support, however there are many today who argue that whilst this is necessary for understanding it is not sufficient.[33] Today adding to a list for potential frames for classification are the adaptionists such as Randolph Nesse and his Evolutionary Medicine. In this subject it is helpful to read the range of intellectual arguments presented in the essays collected by John Brockman.[34]
In defending the construct of ‘Bipolar II disorder’ several correspondents returned to ICD and DSM classifications as if they were as determined as our genetic code. Here it is worth reporting what Dr Allen Frances, said in a recent interview about the delay in formulating DSM 5: “There is no definition of a mental disorder. It’s bullshit. I mean, you just can’t define it.”[35] Dr Frances was the doctor who spear-headed the formulation of the previous version of DSM.
Fifth: necessary but not sufficient.
Evidence base is absolutely necessary for progressing our understanding but many of today’s intellectuals would argue that it is not sufficient. In addition we need intelligent kindness and to embrace the notion of hole ousia, relationships, real world, and the wisdom of the Scotttish physicist James Clerk Maxwell. Or as Edwin Morgan the poet put it: “holding hands amongst the atoms.”
With technological advance, it is understandable why mankind has chosen to view life through the paradigm of illness, when actually what we seek is health. Wholesome humanity must not today approach this back to front, or the result will bring harm.
One respondent suggested: “Dr Spence is right when he suggests that the diagnosis of bipolar II disorder is a real clinical issue. However, an over-diagnosis, whenever possible, doesn’t seem to carry the same negative consequences as an under-diagnosis.”[36] However, it is essential that we do consider the potential harm of over-diagnosis,[37] [38] [39] especially when the USA, our mental weather vane, statistically reveals that the incidence of major depression doubled in a decade from 1992 to 2002.[40]
Sixth: stigma and the Hydra.
Every window views stigma differently. Education here is important, but surely such is not just for patients, but for us all? Stigma grow heads like the Hydra-monster, and it is not the simple case that giving a ‘diagnosis’ reduces stigma. Research in its beginning supports my ‘feeling’ that such is fallacy.[41]
Seventh: primum non nocere
Dr D.J Smith et al claim that up to 21% of primary care patients with depression in fact have unrecognised bipolar disorder, and the authors advise against inappropriate treatment by antidepressants in this significant minority as ‘antidepressants may trigger agitated, mixed or manic mood states.’[42] Other academics have replied stating that this research supports treatment for Bipolar II patients with atypical anti-psychotics such as Quetiapine and the anticonvulsant Lamotrigine.[43]. Such drugs, when appropriately used can reduce suffering, but equally we must consider the side-effects, and realisations of harm that only may appear many years later.[44]
Eighth: Continuing medical education
Professor Nick Craddock, speaking for the 36 academics who asked our profession to ‘wake up’ reaffirmed a collective view: “we are not terribly interested in what is past.”[45]
The Royal College of Psychiatry has embraced the modern, multi-media techniques with its CME modules and podcasts, however look at the content. There is no history, except that of ancient lunacy laws. Where are the considerations of the changing classifications of mental illness, the social and cultural context of mental illness, philosophy[46], the language of science and indeed any ideological considerations beyond the medical model: holism, reductionism, ethics, philosophy, narrative medicine? They just are not there.
Nine million prescribed:
As a citizen of Scotland who was started on an antidepressant during the 1990’s Defeat Depression Campaign, I shall conclude this piece by giving contrasting representations of this campaign as understood by a Professor in tertiary referrals and that of a doctor on the frontline:
Let us start with the former, Professor Reid of Aberdeen stated in one of his replies to Dr Spence: “the Defeat Depression Campaign went some way to improving antidepressant practice, by increasing the dose and duration of antidepressant prescription. This is what resulted in the much misunderstood increase in antidepressant prescriptions: not more people getting antidepressants, but those receiving them getting them – entirely within guideline recommendations.” With the dearth of long-term studies it is hard to see what evidence base the Defeat Depression Campaign based its recommended duration of treatment. Even today, recommended duration of treatment is still far from clear, and there is little clarity about withdrawing treatment.[47]
Professor Reid makes a further most important point: “Simply stating numbers of prescriptions, turns out not to be very informative, but entirely misleading. Indeed, this approach led the Scottish media (and the Government’s Information and Statistics Division) to over-estimate the proportion of the population taking antidepressants by a factor of 5.” Professor Reid then goes on to state that “the quality of care has improved, and even suicide rates may have dropped as a consequence (of the Defeat Depression Campaign)” However, Melissa Raven and Jon Jureidini presented both epidemiological and philosophical argument why we cannot yet be certain that antidepressants have reduced suicide rates. [48]
In contrast, Dr Spence’s experience of the Defeat Depression Campaign: “you will note the large rises in depression diagnosis in the young, rising quickly in the mid nineties, sustained for 7 years and then declining rapidly in 2003. I worked through out this period and anecdotally will tell you what happened. We were berated for under-diagnosing depression and so treated patients. After 5-6 years it was patently obvious that this wasn’t the case and we were over prescribing medication. We lost faith. We had simply medicalised normal reactive behaviour and denied young patients the opportunity to develop coping skills. This is what happened, I was there.”
The truth of this prescriber’s experience is another which should not be ignored. This author has never had bipolar disorder but has suffered from depression and has been on paroxetine since the ‘Depeat Depression Campaign’:
Dr Spence, reminds us that proportionality of understanding comes in words as well as numbers:, “The number of antidepressants prescribed by the NHS in the United Kingdom almost doubled during one decade. There is no evidence that our mental health has improved over this time and plenty to say it hasn’t. I do not celebrate the ever increasing consumption of antidepressants but mourn the poverty of our thinking.” This has been shown to be an argument we do not wish to hear; however it is essential that the humanities (given its classical name) must not be eliminated, and that biological research should never ignore the world we live in. Otherwise the stand-alone brain will fool us all.[49]
Conclusion: windows
It is our very need to ease suffering that brings great passion to debate. This is uniquely human, and a dimension that must never be reduced. Understanding requires that we must see the real world through more than our own window: today’s mental biologism is not enough – it is necessary but not sufficient. Equally quantitative evidence base is necessary but requires qualitative understanding. Here Professor Greenhalgh reminds us that medicine needs narrative more than we like to believe.[50]
[1] Midgley, Mary. Notes. 2003, pp. 26-27.
[2] Brockman, John. Beyond the scientific revolution: The Third Culture. 1st Touchstone Ed edition. May 1996
[3] Spence, Des. Bad Medicine: bipolar II disorder. Frontline article. British Medical Journal. 4th May 2011. 342:d2767
[4] Ilangaratne, Jay. BMJ rapid-response. Condemning Psychiatry, Ideas Based Medicine, and Leading Questions Published 11th May 2011
[5] Rutter, Michael. Challenging psychiatry. Interviewed by Mathew Billingsley. BMJ Careers. 9th February 2011
[6] Craddock, Nick et al. Wake-up call for British psychiatry. The British Journal of Psychiatry, Jul 2008; 193: 6 – 9.
[7] Illich, Ivan Medical Nemesis. 1975
[8] Gordon, Peter J. Gilbert Farie Revisited. A reply to Reply to the Editorial: Has psychopharmacology got a future? May 2011. The British Journal of Psychiatry chose not to publish this.
[9] Population of England in 2010 approximately 51.5 million. Office for National statistics
[10] Population of Scotland in 2010 approximately 5.2 million. General Register Office of Scotland
[11] Hickey, Finlay. Lead Pharmacist Mid Highland CHP. Kindly provided prescribing data on antidepressants for Scotland over the past 5 years.
[12] Moore, Michael, Kendrick, Tony et al. Explaining the rise in antidepressant prescribing: a descriptive study using the general practice research database. British Medical Journal. 15 October 2009. 10.1136/bmj.b3999
[13] Reid, Ian. BMJ Rapid response. Practical considerations. Published 26 May 2011
[14] Reid, Ian. BMJ Rapid response. Truth, not Beauty. Published 27 May 2011
[15] Cowen, Philip. BMJ Rapid response. Constructionism. Published 10 may 2011.”Indeed for some time the ontological status of Spence himself has been contested as a possible BMJ construct: a frontline, not to say “full time”, no nonsense, hard-headed, GP whose very appellation (Dispense) underlines the pervasive reach of big Pharma.”
[16] Moynihan, Ray. Reality Check: It’s time to rebuild the evidence base. British Medical Journal. 2011;342:doi:10.1136/bmj.d3004 (Published 25 May 2011)
[17] Cowen, Philip. Has psychopharmacology got a future?’ British Journal of Psychiatry. 198: 333-335. (Published May 2011)
[18] Cowen, Philip. Has psychopharmacology got a future?’ British Journal of Psychiatry. 198: 333-335. (Published May 2011)
[19] Schmid, Dennis & Schmid, Esther. Keynote review: Is declining innovation in the pharmaceutical industry a myth? DDT, Volume 10, Number 15 (published August 2005) “If you say something often enough, it must be true. Everyone knows that innovation is declining and is the source of all the woes of the pharmaceutical industry. But who has checked the facts? The myth of the innovation deficit is exactly that – a myth”
[20] Cowen, Philip. Has psychopharmacology got a future?’ British Journal of Psychiatry. 198: 333-335. (Published May 2011)
[21] Wieseler, Beate et al. Finding studies on reboxetine: a tale of hide and seek. British Medical Journal 2010;341:doi:10.1136/bmj.c4942 (Published 12 October 2010)
[22] Goldacre, Ben. Bad Science. Fourth Estate (Oct 2008)
[23] Tallis, Raymond. Aping Mankind: Neuromania, Darwinitis and the misrepresentation of humanity. Acumen (published June 2011)
[24] Smith, Richard. Editorial: Medical journals and pharmaceutical companies: uneasy bedfellows British Medical Journal. 326 : 1202 (Published 29 May 2003)
[25] Ban, Thomas. Academic psychiatry and the pharmaceutical industry Progress. Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 429 – 441
[26] Godlee, Fiona. Who should define disease? British Medical Journal;342:doi:10.1136/bmj.d2974. Published 11 May 2011)
[27] Yi, Ming. BMJ Rapid response. Shall we define health first, then diseases? Neuroscience Research Institute, Peking. Published 13 May 2011
[28] Anderson, Ian. BMJ Rapid response: Bad medicine or bad mouthing? British Medical Journal. Published 10 May 2011: “Bipolar II disorder’s current celebrity fashion status feeds into this. But once again this is not confined to psychiatry, and every doctor has to deal with unexplained medical and psychological symptoms. The increasing “tick box” approach to medicine, at the expense of clinical judgement, can only weaken our ability to make a full assessment; this usually needs to incorporate third party information.”
[29] Dowrick, Christopher et al. Patients’ and doctors’ views on depression severity questionnaires incentivised in UK quality and outcomes framework: qualitative study. British Medical Journal. 338:b750 (Published 19 March 2009)
[30] Van Weel, Chris. Incentivised care is no substitute for professional judgment. British Medical Journal. 338:b934 (Published 19 March 2009)
[31] Reid, Ian & Cameron, Isobel. BMJ Rapid response: Depression severity measurement in primary care. Printed 11 April 2009
[32] Marneros, Andreas. Psychiatry’s 200th birthday. British Journal of Psychiatry. 10.1192/bjp.bp.108.051367 February 2008
[33] Tallis, Raymond. The Hand: A philosophical inquiry into
human being (2003) I Am: A Philosophical Inquiry into First-Person Being (2004) The Knowing Animal: A Philosophical Inquiry into Knowledge and Truth (2005) Edinburgh University Press
[34] Brockman, John. Beyond the scientific revolution: The Third Culture. 1st Touchstone Ed edition. May 1996
[35] Greenberg, Gary. Inside the battle to define mental illness. Wired magazine. January 2011
[36] Sani, Gabriele et al. BMJ Rapid response: Bipolar II disorder: bad medicine or bad criticism? Published 31 May 2011
[37] Irwin, Charles et al. America’s adolescents: where have we been, where are we going? Journal of Adolescent Health, Volume 31, Issue 6, Supplement 1, December 2002, Pages 91-121
[38] Robin, A et al. Over-diagnosis and breast cancer screening. European Journal of Cancer Supplements, Volume 4, Issue 2, March 2006, Pages 6-9.
[39] Stephen Jones, J. Prostate Cancer: Are We Over-Diagnosing—or Under-Thinking?
European Urology, Volume 53, Issue 1, January 2008, Pages 10-12
[40] Compton, W. M et al. Changes in the prevalence of major depression and co-morbid substance use disorders in the United States between 1991-1992 and 2001-2002. American Journal of Psychiatry. 163(12):2141-7. Published December 2006
[41] B Rüscha, Nicolas et al. Biogenetic models of psychopathology, implicit guilt and mental illness stigma. Psychiatry Research 179 (May 2010) 328-323
[42] Smith, D. J. et al. Unrecognised bipolar disorder in primary care patients with depression. British Journal of Psychiatry. 10.1192/bjp.bp.110.083840. Published 3 February 2011
[43] Ferrier, Nicol et al. BMJ Rapid response: Bad medicine or bad practice. British Medical Journal. Published 12 May 2011
[44] Committee of Safety of Medicine. March 2004. In March 2004, the UK Committee of Safety of Medicines (CSM) informed clinicians that risperidone and olanzapine should not be used to treat behavioural and psychological symptoms of dementia (BPSD) because of increased risk of strokes with both drugs and increased risk of mortality with olanzapine.
[45] Craddock, Nick et al. Wake up call: Response from authors. Published 19 Oct 2008
[46] Nagel, Thomas. The view from nowhere. ““Philosophy is the childhood of the intellect, and a culture that tries to skip it will never grow up.” Published 1989. OxfordUniversity Press
[47] Burton et al. Newly initiated antidepressant treatment in Scotland. Evidence into Practice. 2010
[48] Isacsson, Göran, & Rich, Charles (For) Jureidini, Jon & Raven, Melissa (Against). IN DEBATE: The increased use of antidepressants has contributed to the worldwide reduction in suicide The British Journal of Psychiatry (2010) 196: 429-433.
[49] Tallis, Raymond. Aping Mankind: Neuromania, Darwinitis and the misrepresentation of humanity. Acumen (published June 2011)
[50] Greenhalgh, Trisha. Soft Rebuttal. Rapid Response British Medical Journal. 31st Dec 2004.
Tony Delamothe: ‘The “truth,” if and when it emerges, will be thanks to the positivist philosophy that underpins quantitative research.’
Trisha Greenhalgh: Is this a declaration of Tony Delamothe’s personal bias or an indication of the BMJ’s editorial position? If the latter, I challenge the BMJ’s Editor to make a formal statement to the effect that:
“Qualitative research is considered by the BMJ to be inherently lower quality than quantitative research. Authors seeking to publish qualitative research should doff their caps accordingly and strive to ensure that their submissions are philosophically nihilist, atheoretical and present a single, unambiguous truth with narrow confidence intervals. Co-authorship with professors of epidemiology will substantially increase the chances of acceptance of qualitative papers.”
Some of the vested interests involved in the “consensus definition” of Bipolar Depression, the British Journal of Psychiatry, January 2019: