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14th LAP Symposium
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Excellence in psychiatry: hopes and
hubris
Over-confident leaders taking excessive risks, the benefits of early treatment of
bipolar disorder, serendipity in the quest for an Alzheimer’s disease treatment
along with strategies to minimise harm from drug therapy all played a part in
the annual meeting for psychiatrists that is the Latest Advances in Psychiatry
Symposium. Steve Titmarsh went along to the Royal College of Physicians in
London, in March to find out more.
14 LATEST ADVANCES IN
PSYCHIATRY SYMPOSIUM
TH
EXCELLENCE IN PSYCHIATRY: HOPES AND HUBRIS
Thursday 12th March 2015
Royal College of Physicians,
Regent’s Park, London
A collaboration between Progress and the International Society for Affective Disorders
Hubris syndrome
The keynote lecture was given by
Lord David Owen. He reviewed
what he had been writing about
hubris syndrome focussing on
diminished empathy and unbridled
intuition and relationships between
the two. Neither is mentioned
directly in the 14 signs and symptoms of hubris syndrome (Table 1)
which Lord Owen developed with
Jonathan Davidson in 2009.1 He
considered how his work might
develop in future in the hope that
he would encourage greater
research into hubris syndrome.
Lord Owen said hubris is an
occupational hazard for political,
military and business leaders.
Company CEOs may be prone to
taking excessive risk and rely more
on intuition than rational thought.
And even though hubristic behaviour may well have played a part in
the downfall of huge international
companies with significant impact
on national economies, there has
been little research into the causes
of the behaviour, neurobiological or
other, let alone potential treatment.
Although risk taking can be
destructive, stifling it completely
and taking a safe approach to business will affect a capitalist economy;
so there is a fine balance to be
struck. Indeed, risk exists in life
and probably has an important role
to play, but it is how risk is handled
that is important, Lord Owen said.
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Lord Owen set up the Daedalus
Trust (www.daedalustrust.com) to
support research into and raise
awareness of personality change
associated with the exercise of
power and the effect on decision
making. However, although he
acknowledged the importance of
medicine and medical treatment,
Lord Owen felt he had to resist the
medical model as a sole answer to
dealing with hubris syndrome as
he feels strongly that a more holistic approach is needed, involving
all facets of human nature, if an
answer to containing and constraining those who develop hubris
syndrome is to be discovered.
Early intervention in bipolar
disorder improves outcomes
It is somewhat surprising that,
compared with schizophrenia,
there are few data on early intervention in bipolar disorder,
indeed, Professor Lars Vedel
Kessing, Professor of Psychiatry at
the
Psychiatric
Centre
Copenhagen and University of
Copenhagen, knew of only one
study. Early intervention has been
shown to result in better outcomes in schizophrenia and
Professor Kessing said there are
seven indications from obser vational studies that early intervention in bipolar disorder may
improve the course and outcome
of the illness:
1. The risk of recurrence increases
with every new episode2
2. Delay to first treatment is associated with more time depressed,
greater severity of depression,
greater number of episodes and
more days of ultrarapid cycling3
3. Response to lithium monotherapy decreases with the occurrence
of multiple prior episodes4
4. The rate of response to lithium
in monotherapy is increased when
started at first psychiatric contact
rather than at later contacts. The
same is true for starting lithium at
the first ever manic episode4
5. Mood stabilisers prescribed for
bipolar disorder may have neuroprotective properties 5,6 so early
inter vention
may
prevent
progression
6. The prevalence of cognitive dysfunction may increase with affective
episodes and the risk of dementia
seems increased by two to three
times over ten to 20 years for
patients with bipolar disorder compared with the general population7
7. Patients may profit from psychoeducation before potential cognitive
disturbances may occur during the
long term course of illness.8
Professor Kessing and colleagues
have tested whether treatment in
a specialised outpatient mood disorder clinic, combining optimised
pharmacological treatment with
group psychoeducation among
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14th LAP Symposium
The Symptoms of Hubris Syndrome
Proposed criteria for Hubris Syndrome and their correspondence
to features of Cluster B personality disorders in DSM-IV
1. A narcissistic propensity to see their world primarily as an
arena in which they can exercise power and seek glory;
2. A predisposition to take actions which seem likely to cast
them in a good light – i.e. in order to enhance their image;
3. A disproportionate concern with image and presentation;
4. A messianic manner of talking about what they are doing
and a tendency to exaltation;
5. An identification of themselves with the nation, or
organisation to the extent that they regard their outlook
and interests as identical;
6. A tendency to talk of themselves in the third person or
using the royal ‘we’;
7. Excessive confidence in their own judgment and contempt
for the advice or criticism of others;
8. Exaggerated self-belief, bordering on a sense of
omnipotence, in what they personally can achieve;
9. A belief that rather than being accountable to the
mundane court of colleagues or public opinion, the court
to which they answer is: History or God;
10. An unshakable belief that in that court they will be
vindicated;
11. Loss of contact with reality; often associated with
progressive isolation;
12. Restlessness, recklessness and impulsiveness;
13. A tendency to allow their ‘broad vision’, about the moral
rectitude of a proposed course, to obviate the need to
consider practicality, cost or outcomes;
14. Hubristic incompetence, where things go wrong because
too much self-confidence has led the leader not to worry
about the nuts and bolts of policy;
NPD.6
NPD.1
NPD.3
NPD.2
Unique
Unique
NDP.9
NPD.1&2
NPD.3
Unique
APD3&5
Unique
Unique
HPD.5
NPD = Narcissistic Personality Disorder only in DSM-IV; APD = Anti Social
Personality Disorder in both DSM-IV & ICD-10; HPD = Histrionic Personality
Disorder in both DSM-IV & ICD-10
Table 1. The symptoms of Hubris Syndrome (Reproduced from Owen D, Davidson J. Hubris
syndrome: An acquired personality disorder? A study of US Presidents and UK Prime Ministers
over the last 100 years. Brain 2009;132:1396–406)
patients discharged after their first,
second or third hospitalisation for
bipolar disorder, is better than
standard psychiatric outpatient
treatment in the early course of
bipolar disorder.9 Patients were followed for up to six years. Time to
readmission was significantly
longer among patients who
received specialised care (n=72)
compared with patients who
received standard care (n=86) (HR
0.60, 95% CI 0.37 – 0.98; p=0.043).
Professor Kessing said that
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represented a substantial effect of
specialised care. In the early days
after discharge when the risk of
suicide, for example, is 240 times
greater than among the general
population, the number of
patients who had specialised care
relapsing was less than among
those treated with standard care.
After two years patients who
received specialised care reverted
to standard care. However,
Professor Kessing pointed out the
relapse rate remained lower than
Progress in Neurology and Psychiatry May/June 2015
among patients who received standard care from the beginning of
the study. That is in contrast to
what is seen in early intervention
in schizophrenia.10
Further analysis of Professor
Kessing’s study revealed that total
time spent in hospital was significantly less for patients who
received specialist care compared
with those who received standard
care (median 33 days vs 49 days;
p=0.01). Patients who had received
specialist care showed greater
adherence to mood stabiliser
(59% vs 32.4%; p=0.001) and
antipsychotic medication (59.5%
vs 34.9%; p=0.01) as reported by
patients at two years.
In economic terms the specialist ser vice makes sense too.
Analysis of two-year treatment costs
show that the total direct net cost
(including saved hospital beds)
was 3,194 Euros less per patient in
the specialist ser vice compared
with standard care, or 11% of the
cost of standard care.
Lastly, Professor Kessing said
there is a general belief that young
patients (under 25 years of age)
with bipolar disorder are difficult
to treat. However, Professor
Kessing’s study shows that outcomes were best for patients aged
18-25 years treated in the mood
disorder clinic (n=29; HR 0.33,
95% CI 0.10-1.07; p=0.064).11
Will we ever have effective
dementia treatments?
One in three people will die with
dementia and virtually everyone
will be touched by it some way,
Professor
Robert
Howard,
Professor of Old Age Psychiatr y
and Psychopathology at King’s
College, London, told the meeting.
In mild, moderate and severe
Alzheimer’s disease cholinesterase
inhibitors offer modest improvements in cognitive function and
activities of daily living (ADL). But
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14th LAP Symposium
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the drugs have no effect on overall
decline.12 And when the drugs are
stopped there is quite a profound
withdrawal effect involving worsening cognition and function and
earlier nursing home placement.13
The evidence for treatment of
behavioural symptoms and psychosis in AD is not as good as that
for cognition and ADL. Only
risperidone has an evidence base
to show that it is convincingly superior to placebo in treatment of agitation, aggression and psychosis in
AD. Indeed, risperidone is the only
drug that has a licence for treatment of aggression in AD in
Europe. And once an antipsychotic
is stopped psychosis returns.14
Disappointingly
the
cholinesterase inhibitors and
memantine are ineffective in treating behavioural symptoms and
psychosis in AD.15
Sadly, despite knowing the
pathology and neuroscience of
dementia and a US$60billion
investment in research by the pharmaceutical industry there is as yet
no sign of disease modifying treatments for AD. Of the 101 drugs
that have come to trial in the last
ten years none have progressed
beyond phase III.
But there may still be hope:
‘Almost all psychiatric treatments
were not discovered through translational development but through
serendipity,’ Professor Howard said.
Repurposing – taking a drug that
has one indication and testing it for
a new indication that it shows some
promise for – could prove fruitful.
One example is a trial with nilvadipine, a calcium-channel blocker
developed for treating hypertension16 which seems to promote
excretion of amyloid in the urine.
Another involves minocycline17 for
which there is evidence of
neuroprotection.
A second glimmer of light is
hippocampal neurogenesis. There
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Figure 1. Comparative efficacy and acceptability of antimanic drugs in acute mania
(Reproduced from: Cipriani, A et al: Comparative efficacy and acceptability of antimanic drugs
in acute mania: a multiple-treatments meta-analysis Lancet 2011; 378:1306-15 (copyright
Elsevier))
is evidence to show that people
produce 700 new neurones a day
in each hippocampus right into
their seventies. 18 If that process
could be stimulated there may be a
benefit in people with AD.
What do the latest guidelines
say about bipolar disorder?
In terms of treatment, there has
been a big shift in the most recent
version of NICE clinical guideline
on bipolar disorder compared with
previous versions.19 While previous
guideline focussed around medications to reduce symptoms, stabilise
mood and prevent relapse, the
new guidance gives much greater
prominence to psychological interventions, Dr Matthew Taylor,
Senior Lecturer at King’s College,
London, told delegates.
The latest NICE guideline
includes a separate section on primary care recognition and management. The guideline does not
recommend using questionnaires
in primary care to identify bipolar disorder in adults (in contrast
to recommendations in the previous edition of the guideline on
secondar y care assessment
advice). Psychological inter ventions for bipolar depression can
be initiated. But primary care initiation of lithium or valproate is
not recommended.
Triggers for referral or re-referral to secondary care are similar to
the previous guideline:
– poor or partial response to
treatment
– functioning declines significantly
– treatment adherence is poor
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– comorbid alcohol or drug misuse
is suspected
– the person is considering stopping any medication after a period
of relatively stable mood.
And two new triggers for referral
or re-referral:
– the person develops intolerable
or medically important side effects
from medication
– a woman with bipolar disorder is
pregnant or planning a pregnancy.
In secondary care, questionnaires
are no longer recommended for
assessment, which Dr Taylor felt was
interesting as he has always found
them quite useful as a starting point.
For mania or hypomania in
people not taking an antipsychotic
or mood stabiliser NICE recommends first-line haloperidol, olanzapine, quetiapine or risperidone.
If the person is already taking
lithium then clinicians should consider adding haloperidol, olanzapine, quetiapine or risperidone,
after checking the patient’s plasma
lithium levels to optimise treatment. A new recommendation is
that lamotrigine should not be
used to treat mania (Figure 1).
For people taking antidepressant monotherapy who develop
mania or hypomania, stopping the
antidepressant should considered
and an antipsychotic offered
whether or not they stop the
antidepressant.
The CANMAT guidelines 20
style is ver y different with quite
complicated algorithms, but
Professor Howard felt they complement the NICE guidelines. BAP
guidelines21 are similar to NICE,
starting with antipsychotics or valproate and recommending lithium
for milder manic symptoms.
Bipolar depression is more
challenging. Recently, with new
treatments and well run trials
there is more hope in this area.
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NICE recommends starting with
psychological interventions such
as those specifically developed for
bipolar disorder that have a published evidence based manual on
how they should be delivered, or a
high intensity psychological intervention (cognitive behavioural
therapy, interpersonal therapy or
behavioural couples therapy) in
line with the NICE clinical guideline on depression.
Dr Taylor commented that the
recommendation to use psychological therapies is perhaps driven less
by evidence, which is mostly of low
or very low quality, and more by
service user demand. One disadvantage of this approach is that it might
impede the development of more
effective treatments, he added.
SSRIs are no longer recommended by NICE for bipolar
depression. An olanzapine / fluoxetine combination or quetiapine
are recommended first-line with
lamotrigine or olanzapine secondline. Some trials seemed have been
missed in the evidence gathered by
NICE. That has been addressed in
an online analysis by Taylor and
colleagues from the Maudsley.22
Relapse prevention is a big
part of bipolar treatment. A new
recommendation in the NICE
guideline for people who have
some
persisting
symptoms
between episodes of mania or
bipolar depression is to offer a
structured psychological intervention (individual, group or family).
Dr Taylor commented that
group therapy seems to be more
effective than one-to-one sessions.23 That’s good news in these
cash-strapped times because group
therapy is a little less expensive to
deliver than the individual format,
he commented.
When planning long-term drug
treatment to prevent relapse the
NICE guideline says clinicians
should discuss with people
Progress in Neurology and Psychiatry May/June 2015
whether they want to stay with their
current treatment or switch to
lithium. It should be explained
that lithium is the most effective
long-term treatment for bipolar
disorder. Dr Taylor commented: ‘I
am a great fan of lithium. I think
it’s probably underused but I am
not entirely sure whether you can
say it’s the most effective long-term
treatment for bipolar disorder.’24
Indeed, in Dr Taylor’s opinion, the
options for long-term treatment
recommended by NICE are fairly
limited: lithium first line with the
addition of valproate if it is ineffective. Valproate or olanzapine are
recommended for those patients
who do not tolerate lithium or do
not agree to routine blood monitoring, or a new recommendation,
to offer quetiapine for those who
responded during an episode of
mania or bipolar depression.
Dr Taylor concluded by saying
it is clear now that treatments for
bipolar disorder are not like-forlike equivalents. They differ in clinically important ways and in terms
of efficacy. And the drugs that
work for the acute phase seem to
work in a proportionate way in the
long term.25
Risk management of medicines
Professor Saad Shakir, Director of
the Drug Safety Research Unit in
Southampton, discussed some of
the strategies employed to monitor medicines and to try to reduce
some of associated risks when they
move from the somewhat artificial
realms of clinical trials into the real
world where they may be taken by
patient groups who may not have
been represented in trials.
Pharmacovigilance and risk
management are important
because:
• 5% of all hospital admissions are
for ADRs26
• 5% of all hospital inpatients suffer an ADR
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14th LAP Symposium
• ADRs are the 5th most common
cause of hospital death
• Estimated 197,000 deaths in the
EU from ADRs
• EU societal cost of ADRs is 79 billion Euros per year
Clinical trials are limited in their
ability to pick up adverse reactions
to drugs, not least because they
often include too few patients,
inclusion criteria are too restrictive, they run for too short a time
and do not reflect real world practice.
Thus when a drug is used in the
wider world it is important risk
management is instituted which
involves a set of pharmacovigilance
activities and inter ventions
designed to identify, characterise,
prevent or minimise risks relating
to medicinal products, including
the assessment of the effectiveness
of those interventions.
Secondary care event monitoring studies are one means by which
pharmacovigilance data can be
captured. Many of these are
required as part of the licensing of
some drugs.
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acquired personality disorder? A study of US
Presidents and UK Prime Ministers over the last
100 years. Brain 2009;132:1396–406.
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Course of illness in depressive and bipolar disorders. Naturalistic study, 1994-1999. Br J
Psychiatry 2004;185:372-7.
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