Bad medicine: bipolar II disorderBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d2767 (Published 04 May 2011) Cite this as: BMJ 2011;342:d2767
All rapid responses
Can't agree more. Psychosocial interventions for bipolar disorder is a necessity and the work of Dr Ellen Frank (http://www.psychology.pitt.edu/people/faculty/faculty.php?fc_id=16), Dr Scott (http://www.ncl.ac.uk/ion/staff/profile/jan.scott) and Dr Eden Fazek (Bipolar Expert Info: www.edengalaxy.com) clearly demonstrates it. We, the members of the psychiatry profession, should put every effort into combining pharmacotherapy with psychosocial methods of management of bipolar disorder if we want to see long lasting remissions in our patients.
Competing interests: No competing interests
The views of Des Spence (1) on the increase in the diagnosis of
Bipolar II disorder is of enormous importance as it raises pertinent
issues and generates much debate.
Diagnostic categories in Psychiatry are not based on aetiology but on
symptom clusters. Hence validity and reliability remains an issue. The
increase in the diagnosis of Bipolar II over recent years is due to a
multiplicity of reasons.
Bipolar disorder appears to have become fashionable as media figures
such as Steven Fry and Kerry Katona have publicised their conditions.
This has reduced the stigma attached to Bipolar disorder and the public
have, consequently, become more accepting of this condition. The public
are also more aware and educated on these conditions as they have
increased access to the internet. Unfortunately, some of these sites are
not governed and may give an inaccurate reflection of the condition. It
is now common for patients to come to the interview with a list of their
symptoms and showing a comparison with what they have read. This in a way
is similar to filling in a questionnaire as mentioned by Des Spence.
Prior to the interview they would have already convinced themselves that
they suffer from the disorder.
Psychiatrists are trained to make a diagnosis based on comprehensive
history taking including psychological and social aspects, longitudinal
knowledge of the patient, collateral information and objective evidence.
They do not rely solely on questionnaires to make a diagnosis.
Furthermore, Psychiatrists do not make such a diagnosis lightly as they
are aware of the side effects of the medication and are aware that the
medication is often used on a long term basis.
Patients often become upset when they are informed that they do not
have Bipolar disorder. This disappointment could be for a number of
reasons. Firstly, it could because their expectations are not met as they
were anticipating a medical cure. Perhaps it could be that in some cases
such a diagnosis may have a more favourable outcome when applying for
benefits in these times of austerity. Furthermore a proportion of these
individuals have other conditions such as personality disorders and
comorbid issues with consuming excessive alcohol or drugs, and Bipolar
disorder may be more acceptable diagnosis. Psychiatrists are thereby
placed in a very difficult position when there opinion is at variance with
that of the individual.
The increase in the diagnosis, the consequences as mentioned by Des
Spence and the difficulties for Psychiatrists will continue to remain a
problem till such time that we have an aetiological diagnosis.
Competing interests: No competing interests
In his article, Dr. Des Spence suggested that we are on the cusp of a
massive increase in the diagnosis of bipolar II, with prescribing more
mood stabilizers.1 This has lead to widespread discussion and debate about
the bipolar spectrum, which incorporates classic bipolar disorder, bipolar
II disorder, and bipolar III disorder that is not an official diagnosis
recognized by psychiatric associations. We will not find bipolar III
disorder mentioned in the International Classification of Diseases (ICD-10) or Diagnostic and Statistical Manual of the American Psychiatric
Association (DSM-IV). However, some psychiatric professionals use the
unofficial diagnosis of bipolar III disorder to describe patients who have
experienced manic or hypomanic episode due to antidepressant treatment.
Similarly to bipolar II disorder, bipolar III disorder, is an additional
problem that may be described by Dr. Spence as a 'intellectual construct
of modern psychiatry, -neither fact nor science'. However, up to 21% of
primary care patients with depression have in fact unrecognised bipolar
disorder and antidepressant-associated mania has been linked to all major
antidepressant classes in a subgroup of 20-40% of bipolar patients.1,2
Even some kind of antiobesity drugs e.g. sibutramine (serotonin-,
norephiephrine-, and, dopamine- reuptake inhibitor), may induce mania -as
the first manifestation of bipolar disorder- in predisposed individuals by
acting in a similar way with other antidepressant drugs (e.g. selective
serotonine reuptake inhibitors -SSRIs).3 Sibutramine was initially
intended as an antidepressant drug in the 1980s.4 It is a 'fact and
science' that the serotonin transporter gene is a candidate to be
associated with antidepressant-associated mania in some patients.5 This
gene has a polymorphism within the promoter region (5-HTTLPR) with two
allelic forms -the long and the short variants. Since 5-HTTLPR
polymorphism is considered as a predictor of abnormal response to
antidepressant in vulnerable to bipolar disorder patients, a correct
diagnosis of bipolarity and detailed family history for affective
disorders should be done before the beginning of depression treatment. It
is essential mainly for short variant of 5-HTTLPR carriers.
Dr. Spence suggested that the diagnose of hypomania based on
questionnaires may be subject to a variety of biases, may be leading and
suggestive. Is psychiatry causing more iatrogenic harm than good? Is
rampant overdiagnosis now the real issue? - Dr. Spence asked. Psychiatry
is not iatrogenic and there is no overdiagnosis when diagnosed properly.
The criteria of bipolar disorder have been established to decrease
overdiagnosis of hypomanic episodes and the incorrect classification of
patients with major depressive disorder as a patients with bipolar
disorder. Questionnaires are very helpful but the diagnosis in psychiatry
is mainly based on clinical careful assessment of patient's mental state
and detailed family history for psychiatric disorders. Only suffering
bipolar patient should be treated (or when his/her family suffers). Hence,
all aspects of bipolarity treatment require careful weighting, and
benefits of pharmacotherapy must outweigh the risks and costs.
1. Spence D. Bad medicine: bipolar II disorder. Bmj. 2011;342:d2767.
2. Goldberg JF, Truman CJ. Antidepressant-induced mania: an overview of
current controversies. Bipolar Disord 2003; 5: 407-420.
3. Cordeiro Q, Vallada H. Sibutramine-induced mania episode in a bipolar
patient. Int J Neuropsychopharmacol 2002; 5: 283-284.
4. Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat,
sibutramine, and rimonabant. Lancet 2007; 369: 71-77.
5. Benazzi F. Organic hypomania secondary to sibutramine-citalopram
interaction. J Clin Psychiatry 2002; 63: 165.
We declare that we have no conflicts of interest.
Competing interests: No competing interests
Part 3: A reply to the Frontline article 'Bad Medicine: bipolar II
disorder' and the responses it attracted
Five million reasons: necessary but not sufficient.
Evidence base is necessary for progressing our understanding but many
of today's intellectuals would argue that it is not sufficient.
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.
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."(1) However, it is essential that we
do consider the potential harm of over-diagnosis.(2,3,4)
Six million reasons: 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.(5)
Seven million reasons: 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.'(6) 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.(7) Such
drugs, when appropriately used reduce suffering, but equally we must
consider potential side-effects, and realisations of harm that only may
appear many years later.(8)
Eight million reasons: 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."(9)
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 suffering, philosophy,(10) the
language of science and indeed any ideological considerations beyond the
medical model: holism, reductionism, ethics, philosophy, narrative
medicine? They just are not there.
The humanities (given its classical name) must not be marginalised,
and biological research must include the world we live in. Otherwise the
stand-alone brain will fool us all.(11)
Nine million prescribed:
As a citizen of Scotland who was started on an antidepressant during
the 1990's Defeat Depression Campaign, I shall conclude by giving
contrasting representations of this campaign as understood by a Professor
in tertiary referrals and that of a doctor on the frontline. Here
Professor Greenhalgh reminds us that medicine needs narrative more than we
like to believe.(12)
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
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 continued: "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.(14)
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."
It is surely a struggle to leave aside Dr Spence's unecessarily
abrupt style, but he does force upon us a necessary reminder: that
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.
(1) Sani, Gabriele et al. BMJ Rapid response: Bipolar II disorder:
bad medicine or bad criticism? Published 31 May 2011
(2) 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
(3) Robin, A et al. Over-diagnosis and breast cancer screening.
European Journal of Cancer Supplements, Volume 4, Issue 2, March 2006,
(4) Stephen Jones, J. Prostate Cancer: Are We Over-Diagnosing--or
European Urology, Volume 53, Issue 1, January 2008, Pages 10-12
(5) B Ruscha, Nicolas et al. Biogenetic models of psychopathology,
implicit guilt and mental illness stigma. Psychiatry Research 179 (May
(6) 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
(7) Ferrier, Nicol et al. BMJ Rapid response: Bad medicine or bad
practice. British Medical Journal. Published 12 May 2011
(8) Committee of Safety of Medicine. March 2004. In March 2004, the
UK Committee of Safety of Medicines (CSM).
(9) Craddock, Nick et al. Wake up call: Response from authors.
Published 19 Oct 2008
(10) 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. Oxford University Press
(11) Tallis, Raymond. Aping Mankind: Neuromania, Darwinitis and the
misrepresentation of humanity. Acumen (published June 2011)
(12) 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."
(13) Burton et al. Newly initiated antidepressant treatment in
Scotland. Evidence into Practice. 2010
(14) Isacsson, G?ran, & 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.
Competing interests: I have been taking paroxetine since 1997.I studied in Arts at Edinburgh University.
Part two: a reply to the Frontline article 'Bad Medicine: bipolar II
disorder' and the responses it attracted
In the second part of my response, I will present the first four of
nine reasons, one per million, open of course to debate, why mankind
should consider the arguments stirred frontline.
One million reasons: 'truth.'
This small, but powerful word was used repeatedly by respondents in
their opposing argument to Dr Des Spence.(1) Truth as it relates to
evidence-based medicine will be the subject of the forthcoming December
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.(2) 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
Professor Cowen's laugh-aloud 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.(4) In this editorial Cowen
described past British Medical Journal coverage on antidepressants as
'deranged'(4) Professor Cowen entitled his response to Dr Spence's
frontline 'constructionism'; however his editorial in the British Journal
of Psychiatry (4) 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.(5)
In 2008, Dr Ben Goldacre published 'Bad Science'(6) 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.'(7)
Dr Richard Smith, former Editor of the British Medical Journal
departed office in 2003 with his own concern: Medical journals and
pharmaceutical companies: uneasy bedfellows.(8) In his 'goodbye', Dr Smith
warned of confounding marketing with medical education. In terms of
Academic Psychiatry this subject was given careful consideration by Thomas
Two million reasons: 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,(10) 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.(11) It appears to be emerging that this awful
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
Three million reasons: 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.(12) 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, general practitioners are
rewarded for using validated questionnaire measures of the severity of
depression at the outset of treatment. Qualitative evidence reveals that
general practitioners doubt the validity of the measures and use their
clinical judgment to decide about treatment regardless of patients'
questionnaire scores.(13) 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."(14) 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
Four million reasons: all that is classified.
There is one perennial conundrum that has always pre-occupied
psychiatry: the classification of mental suffering. The search for
biological markers will go on, and it is a cause we should support,
however whilst this is necessary for understanding it is not sufficient.
As Dr Allen Frances, the man who spear-headed the development of the most
recent version of the Diagnostic Statistical Manual (DSM IV, also known as
the 'Bible' at least for psychiatrists), recently said 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."(16)
(1) Reid, Ian. BMJ Rapid response. Truth, not Beauty. Published 27
(2) Cowen, Philip. BMJ Rapid response. Constructionism. Published 10
(3) 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)
(4) Cowen, Philip. Has psychopharmacology got a future?' British
Journal of Psychiatry. 198: 333-335. (Published May 2011)
(5) 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)
(6) Goldacre, Ben. Bad Science. Fourth Estate (Oct 2008)
(7) Tallis, Raymond. Aping Mankind: Neuromania, Darwinitis and the
misrepresentation of humanity. Acumen (published June 2011)
(8) Smith, Richard. Editorial: Medical journals and pharmaceutical
companies: uneasy bedfellows British Medical Journal. 326 : 1202
(Published 29 May 2003)
(9) Ban, Thomas. Academic psychiatry and the pharmaceutical industry
Progress. Neuro-Psychopharmacology & Biological Psychiatry 30 (2006)
429 - 441
(10) Godlee, Fiona. Who should define disease? British Medical
Journal;342:doi:10.1136/bmj.d2974. Published 11 May 2011)
(11) Yi, Ming. BMJ Rapid response. Shall we define health first, then
diseases? Neuroscience Research Institute, Peking. Published 13 May 2011
(12) Anderson, Ian. BMJ Rapid response: Bad medicine or bad mouthing?
British Medical Journal. Published 10 May 2011:
(13) 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)
(14) Van Weel, Chris. Incentivised care is no substitute for
professional judgment. British Medical Journal. 338:b934 (Published 19
(15) Reid, Ian & Cameron, Isobel. BMJ Rapid response: Depression
severity measurement in primary care. Printed 11 April 2009
(16) Greenberg, Gary. Inside the battle to define mental illness.
Wired magazine. January 2011
Competing interests: I have been taking paroxetine since 1997.I studied an Arts degree at Edinburgh University.
A reply to the Frontline article 'Bad Medicine: bipolar II disorder'
and the responses it attracted
"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. 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 as much concern as it did support.(6)
Rather than getting embroiled in the well-rehearsed arguments over
the status of Bipolar II, I would like to focus on the underlying theme of
Dr Spence's frontline. He returns primarily to the medicalization of
today. 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)
Last year 40 million prescriptions of antidepressants were issued in
England(8) and 4.5 million in Scotland.(9) 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 (40 million) and Scotland (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.(10) Of
course the true estimate will be considerably lower as revealed by Moore
and colleagues, (11) 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 the second part of my response, I will present 9 reasons, one per
million, open of course to debate, why mankind should not simply dismiss
the 'cod philosophy'(12) of Dr Spence.
(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) Population of England in 2010 approximately 51.5 million. Office
for National statistics
(9) Population of Scotland in 2010 approximately 5.2 million. General
Register Office of Scotland
(10) Hickey, Finlay. Lead Pharmacist Mid Highland CHP. Kindly
provided prescribing data on antidepressants for Scotland over the past 5
(11) 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.
(12) Reid, Ian. BMJ Rapid response. Practical considerations.
Published 26 May 2011
Competing interests: I have been taking Paroxetine since 1997. I studied Arts at Edinburgh University.
The apparent scepticism and possible disdain shown by GP Dr Des
Spence for some psychiatric diagnoses and evidence-based treatments,
particularly with regard to bipolar II disorder, may not be exclusive to
hard-bitten primary care practitioners such as himself.
From our experience of working in both primary and secondary care in
inner London, a significant number of 'jobbing' psychiatrists also seem
doubtful about the seriousness and diagnostic importance of bipolar II
disorder, and the need to manage patients who suffer from it in a
comparable fashion to those with bipolar I disorder.
This is based on our impression that in every day clinical practice,
psychiatrists tend to avoid using ICD or DSM diagnoses in general and that
of bipolar II disorder in particular. Accordingly, it has not been unusual
for us to come across the use by psychiatrists of antidepressant
medication without additional mood stabilisers or atypical antipsychotics
in moderately to severely depressed patients who also have a history of
episodes of clinically significant mood elevation. We can speculate that
our encountering relatively large numbers of manic patients, and patients
with atypical treatment resistant depression or rapid cycling mood
disorder, may be partly due to inappropriate drug treatment of bipolar II
disorder by both GPs and psychiatrists.
This implies to us that the contraversial, but no doubt influential
views held by Dr Spence on this subject are shared by some, possibly many
general psychiatrists. The challenge of convincing medical practitioners
of the significance and seriousness of bipolar II disorder, and the
special considerations necessary for treating depression in this disorder,
may therefore be even greater than many experts and opinion-leaders
Dr Phil Harrison-Read, Retired Consultant Psychiatrist; Dr Barbara
Woodhatch, General Practitioner
Competing interests: No competing interests
We read with great interest the reflections by Dr. Des Spence's
letter 1. Nevertheless, his thoughts appear to be not evidence-based.
Strangely enough, he, as a GP, suggests that the great majority of
psychiatric diagnoses are mere intellectual exercises ("Modern psychiatry
is merely an intellectual construct, neither fact nor science. Psychiatry
uses crude generalisations to generate models to explain the unexplainable
and to know the unknowable") and he reports the increase of diagnosis of
bipolar II disorder as a proof of what seems more a prejudice than a
scientific and evidence-based opinion. This statement is dangerous and
unacceptable for several reasons. But this is not new: psychiatry,
psychiatrists, and psychiatric patients have always been victims of
stigmatizations and prejudices.
Dr. Spence basically questions the clinical significance and
construct validity of hypomania and bipolar II disorder that are official
diagnostic categories in ICD-10 and DSM-IV 2 3.
However, the separation of unipolar depression from bipolar (manic-
depressive) disorder as well as the subdivision of bipolar disorder
further into bipolar I and bipolar II subtypes, has been accepted for many
years 4-6. Several studies have demonstrated that bipolar II disorder
represents a quite common, clinically and biologically distinct form of
major mood disorders that should be separated both from bipolar I and, of
course, from unipolar major depressive disorder 5 7-12, and that bipolar
II disorders show the same, or even worse, psychiatric and social
consequences as do bipolar I and unipolar patients 4 6 10 11.
As far as bipolar type II is concerned, one should know exactly what
s/he is talking about before presenting any personal - and particularly
basically critical - idea. Since the very beginning 13, researchers
collected a growing amount of biological and clinical data regarding the
bipolar I-bipolar II distinction. Nowadays, what we know is that patients
with bipolar II disorder, compared to patients with bipolar I, are more
likely to be female 14, have less severe but more frequent and more
chronic depressions 10, a shorter interepisode time, a longer time spent
in depression 10, a higher number of episodes 15, a higher risk of
attempting and completing suicide 16 17, and more comorbid anxiety and
alcohol abuse 18. Moreover, patients with bipolar II disorder are more
likely to become rapid cyclers, thus is having at least four affective
episodes per year 5 19 20 , and to develop mixed affective states,
particularly agitated depression 21. One should know that many researchers
6 19 22 23 believe that the risk of developing rapid cycling, mixed states
and suicidality may increase when antidepressants are used in patients
with an unrecognized bipolar disorder. The mis/under-diagnosis of bipolar
disorder concerns more bipolar II than bipolar I patients. This
underdiagnosis is more common than overdiagnosis, and may have tragic and
sometimes fatal consequences 24.
Dr. Spence writes: "The diagnosis of hypomania in bipolar II disorder
is not a model that I as a clinician can accept.......Doctors should know
whether or not the diagnosis of hypomania has any real world validity."
Hypomania is a strictly defined condition that markedly differs from
one's usual mood and activity level as well as from manic episode 2 3.
Major depression with hypomania but not with mania was first referred as
bipolar II disorder in 1970 13 and, as a result of several subsequent
clinical studies 25, it became an official diagnosis in the 4th edition of
the Diagnostic and Statistical Manual of Mental Disorders of the American
Psychiatric Association 17 years ago 3. Hypomania and mania are also
described as two distinct syndromes in the WHO classification of diseases
2. Is it the official reflection of bad medicine?
Based on co-rated interviews, test-retest interviews and best-
estimate diagnostic procedures, it has been shown that hypomania and
bipolar II disorder are quite reliable and stable diagnostic categories
(Cohen kappa coefficients: 1.0, 0.72, and 0.99, respectively) 26.
Community based epidemiological studies show that lifetime prevalence of
DSM-IIIR/DSM-IV defined bipolar II disorder in the United States and in
Europe is "only" between 0.4 and 2.0 percent 27 28, and re-analysing the
US-National Comorbidity Survey database in the light of the clinical
significance criterion it has been found that while the past-year
prevalence of unipolar major depression decreased substantially (8.9% vs
5.4%%) the figures for bipolar II and bipolar I disorders remained exactly
the same (0.2% vs 0.2%, and 1.3% vs 1.3%, respectively) 29.
Dr. Spence writes: ?For bipolar II I could find little evidence on drug
treatment and no long term data"
This is quite surprising, as the scientific literature on drug treatment
of bipolar II disorder is voluminous, including several (up to 13 year
long) long-term studies showing that pharmacotherapy of bipolar II
disorder is more beneficial than placebo or no treatment 25 30.
Dr. Spence mentions "there were 40 million prescriptions for
antidepressants in England in 2010. No family is untouched, but have these
medications made us happier?"
Everybody should know that the goal of antidepressant pharmacotherapy
is not to make persons happier, in general, but rather to treat patients
with depressive disorders, patients who are really ill, experiencing
symptoms including sadness, loss of pleasure, sleep and appetite
disturbances, etc. The 40 million prescriptions of antidepressants in
England in 2010 do not mean 40 million people. The average number of
prescriptions for one patient per year is 5-6, Therefore, the number of
patients who received antidepressant pharmacotherapy in England in 2010
should be no more than 7-8 million. Given the fact that the one-year
prevalence of major depressive disorder in the population is around 6-8 %,
25 and that antidepressants are also indicated for treating anxiety and
some other psychiatric disorders, this figure is acceptable.
At the end of his paper Dr. Spence puts forward the questions: "Is
psychiatry causing more iatrogenic harm than good? Is rampant
overdiagnosis now the real issue? These are questions for all doctors."
Dr. Spence's concern about overdiagnosis of bipolar disorder is
interesting, particularly as he was the very person who quoted the recent
paper from UK supporting several prior findings on the underdiagnosis of
Dr. Spence is right when he suggests that the diagnosis of bipolar II
disorder is a real clinical issue. However, an overdiagnosis, whenever
possible, doesn't seem to carry the same negative consequences as an
underdiagnosis. First of all, underdiagnosis of bipolar patients can lead
doctors to an overprescription of antidepressant treatments with a
potential worsening of the course and clinical picture of the disorder, as
we mentioned before. Secondly, it's very well known that newly recognized
medical disorders catch the attention of clinicians and researchers. The
distinction between bipolar I and bipolar II is similar to the
categorization of diabetes into types I and II. Some decades ago after
discovering a syndrome of elevated blood sugar level that develops in
later life and is insulin resistant which was named as type II diabetes,
this diagnosis has increased rapidly without any concern of its
overdiagnosis. Type I or type II diabetes as a condition making a life
sentence for pharmacotherapy has never been questioned, while such
procedure for relieving the burden of bipolar II disorder is considered by
the author as a sign of "bad medicine". Furthermore, currently both
lithium and lamotrigine may be more suitable for such a long- term
treatment than valproate or even quetiapine, mentioned by Dr. Spence.
Of course, criticism, by competent persons, is always necessary but
it should be done at an appropriate level.
Gabriele Sani, (email@example.com; Department of
Neurosciences, MentalHealth and SensoryOrgans, Sant'Andrea Hospital,
Sapienza University of Rome, Rome 00189, Italy and Centro Lucio Bini,
Zoltan Rihmer (firstname.lastname@example.org; Department of Clinical and
Theoretical Mental Health, Kutvolgyi Clinical Centre, Semmelweis
University, Faculty of Medicine, Budapest, Hungary)
Xenia Gonda (email@example.com; Department of Clinical and
Theoretical Mental Health, Kutvolgyi Clinical Centre, Semmelweis
University, Faculty of Medicine, Budapest, Hungary and Department of
Pharmacodynamics, Semmelweis University, Faculty of Pharmacym Budapest,
Maurizio Pompili (firstname.lastname@example.org; Department of
Neurosciences, MentalHealth and SensoryOrgans, Suicide PreventionCenter,
Sant'Andrea Hospital, Sapienza University of Rome, Rome 00189, Italy and
McLean Hospital, Harvard Medical School, Boston, MA 02478, USA)
Janusz Rybakowski (email@example.com; Department of Adult
Psychiatry, Poznan University of Medical Sciences, Poznan, Poland)
1 Spence D. Bad medicine: bipolar II disorder. Bmj. 2011;342:d2767.
2 WHO. International Classification of Diseases, 10th revision (ICD-
10). Geneva: World Health Organization; 1992.
3 APA. Diagnostic and Statistical Manual of Mental Disorders, 4th
edition, (DSM-IV). Washington DC: American Psychiatric Association; 1994.
4 Rihmer Z, Angst J. Epidemiology of bipolar disorder. In: Kasper S,
Hirschfeld RMA, editors. Handbook of Bipolar Disorder. New York: Taylor
and Francis; 2005. p. 21-35.
5 Coryell W. Bipolar II disorder: a progress report. J Affect Disord.
1996 Dec 16;41(3):159-62.
6 Benazzi F. Bipolar disorder--focus on bipolar II disorder and mixed
depression. Lancet. 2007 Mar 17;369(9565):935-45.
7 Angst J, Frey R, Lohmeyer B, Zerbin-Rudin E. Bipolar manic-
depressive psychoses: results of a genetic investigation. Hum Genet.
8 Goodwin FK, Jamison KR. Manic-Depressive Illness. New York: Oxford
University Press; 1990.
9 Benazzi F, Akiskal HS. Clinical and factor-analytic validation of
depressive mixed states: A report from the Ravenna-San Diego
collaboration. Curr Opin Psychiatry. 2003;16:s71-s8.
10 Judd LL, Akiskal HS. The prevalence and disability of bipolar
spectrum disorders in the US population: re-analysis of the ECA database
taking into account subthreshold cases. J Affect Disord. 2003 Jan;73(1-
11 Judd LL, Akiskal HS, Schettler PJ, Coryell W, Maser J, Rice JA, et
al. The comparative clinical phenotype and long term longitudinal episode
course of bipolar I and II: a clinical spectrum or distinct disorders?
Journal of affective disorders. 2003 Jan;73(1-2):19-32.
12 Liu JX, Chen YS, Hsieh JC, Su TP, Yeh TC, Chen LF. Differences in
white matter abnormalities between bipolar I and II disorders. J Affect
Disord. 2010 Dec;127(1-3):309-15.
13 Dunner DL, Gershon ES, Goodwin FK. Heritable factors in the
severity of affective illness. Biol Psychiatry. 1976 Feb;11(1):31-42.
14 Cassano GB, Dell'Osso L, Frank E, Miniati M, Fagiolini A, Shear K,
et al. The bipolar spectrum: a clinical reality in search of diagnostic
criteria and an assessment methodology. J Affect Disord. 1999
15 Akiskal HS, Benazzi F. Atypical depression: a variant of bipolar
II or a bridge between unipolar and bipolar II? J Affect Disord. 2005
16 Pompili M, Rihmer Z, Innamorati M, Lester D, Girardi P, Tatarelli
R. Assessment and treatment of suicide risk in bipolar disorders. Expert
Rev Neurother. 2009 Jan;9(1):109-36.
17 Rihmer Z. Depression and suicide and attempted suicide. In:
O'Connor R, Platt S, Gordon J, editors. International Handbook of Suicide
Prevention: Research, Policy and Practice. Oxford: Wiley Blackwell; 2011.
18 Ferrier IN, Mac MI, Young AH. The search for the wandering
thymostat: a review of some developments in bipolar disorder research. Br
J Psychiatry. 2001 Jun;178(Suppl 41):S103-6.
19 Koukopoulos A, Reginaldi D, Laddomada P, Floris G, Serra G, Tondo
L. Course of the manic-depressive cycle and changes caused by treatment.
Pharmakopsychiatr Neuropsychopharmakol. 1980;13(4):156-67.
20 Koukopoulos A, Sani G, Koukopoulos AE, Minnai GP, Girardi P, Pani
L, et al. Duration and stability of the rapid-cycling course: a long-term
personal follow-up of 109 patients. J Affect Disord. 2003 Jan;73(1-2):75-
21 Koukopoulos A, Albert MJ, Sani G, Koukopoulos AE, Girardi P. Mixed
depressive states: nosologic and therapeutic issues. Int Rev Psychiatry.
22 Rihmer Z, Akiskal H. Do antidepressants t(h)reat(en) depressives?
Toward a clinically judicious formulation of the antidepressant-
suicidality FDA advisory in light of declining national suicide statistics
from many countries. J Affect Disord. 2006 Aug;94(1-3):3-13.
23 Sani G, Tondo L, Koukopoulos A, Reginaldi D, Kotzalidis GD,
Koukopoulos AE, et al. Suicide in a large population of former psychiatric
inpatients. Psychiatry Clin Neurosci. 2011 Apr;65(3):286-95.
24 Dunner DL. Clinical consequences of under-recognized bipolar
spectrum disorder. Bipolar Disord. 2003 Dec;5(6):456-63.
25 Goodwin FK, Jamison KR. Manic-Depressive Illness. Bipolar
disorders and recurrent depression. New York: Oxford University Press;
26 Simpson SG, McMahon FJ, McInnis MG, MacKinnon DF, Edwin D,
Folstein SE, et al. Diagnostic reliability of bipolar II disorder. Arch
Gen Psychiatry. 2002 Aug;59(8):736-40.
27 Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM,
Petukhova M, et al. Lifetime and 12-month prevalence of bipolar spectrum
disorder in the National Comorbidity Survey replication. Arch Gen
Psychiatry. 2007 May;64(5):543-52.
28 Pini S, de Queiroz V, Pagnin D, Pezawas L, Angst J, Cassano GB, et
al. Prevalence and burden of bipolar disorders in European countries. Eur
Neuropsychopharmacol. 2005 Aug;15(4):425-34.
29 Narrow WE, Rae DS, Robins LN, Regier DA. Revised prevalence
estimates of mental disorders in the United States: using a clinical
significance criterion to reconcile 2 surveys' estimates. Arch Gen
Psychiatry. 2002 Feb;59(2):115-23.
30 Amsterdam JD, Shults J. Efficacy and safety of long-term
fluoxetine versus lithium monotherapy of bipolar II disorder: a
randomized, double-blind, placebo-substitution study. Am J Psychiatry.
Gabriele Sani: none.
Zoltan Rihmer has received speakers' honoraria from AstraZeneca, GSK, Lilly, Lundbeck, Organon, Pfizer, Richter, Sanofi-Aventis, Servier-EGIS and Wyeth Pharmaceuticals. He alse served as member of the scientific advisory board for AstraZeneca, Lilly, Organon, Pfizer, Richter, Sanofi-Aventis and Servier-EGIS.
Xenia Gonda has received travel support fro GSK, Krka, Lilly, Montrose, Organon, Richter Sanof-Aventis and Schering-Plough.
Maurizio Pompili: Dr. Pompili has been a consultant to or has received research support from Eli Lilly and Organon.
Janusz Rybakowski: JKR has acted as a consultant or as a speaker for Adamed-Poland, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Organon, Pfizer, Sanofi -Aventis, and Servier
Competing interests: Gabriele Sani: none.
Des, you are an evidence impermeable mystic! You say "We need work ,
purpose, community, faith, family, friends and security. Making people
happy is not in our gift and we are in denial if we believe it is." Well
I've no doubt that's right. But people still get sick, and depressive
disorder is as bad as it gets. And work, purpose, community, faith,
family, friends and security can't make it better. That is why it is such
a cruel, misunderstood, illness. Over and out.
Competing interests: Has worked both as paid and unpaid consultant to government; mental health charities; NHS; pharmaceutical industry; voluntary organisations
Thanks for responding again. Although the numbers seem to decline 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 happen. We were berated for underdiagnisising depression and
so treated patients. After 5-6 years it was patently obvious that this
wasn't the case and we 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.
Also you haven't adquetaely adressed the recent 40% rise for this is
represents millions apon millions of prescriptions and patients.What part
of that is misleading ?
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.To suggest it is a question of merlye turning up Serotonin is
dismissive of all human existence and evolution. We need work , purpose,
community, faith, family, friends and security.Making people happy is not
in our gift and we are in denial if we believe it is.
There other absolutely fundamental issues. Are antidepressants
much better than placebo? Research suggest not. Has the evidence base
been distorted for profit? Research suggests so . Do we know the long
term benefits of antidepressants and safety? No we do not.
Thanks for responding but we clearly just have different faith
systems. I might be wrong but so could you. Let time be the judge.
Competing interests: No competing interests