Conference report I 18th LAP symposium
18th Latest Advances in Psychiatry
Symposium
The 2019 Latest Advances in
Psychiatry Symposium was held
in March at the Royal College
of Physicians, London, with the
theme ‘Mental health after
Brexit: from psychosis to
borderline personality
disorders’. Here, Felix David
covers highlights on the opioid
overdose crisis, severe
personality disorder,
neurosurgery for severe mental
illness, generalised anxiety
disorder and burnout in
medical staff.
The opioid overdose crisis:
exploring potential new
elements of response
The opioid overdose epidemic has
been well documented in the USA,
with statistics showing it is also
occurring in the UK. Professor Sir
John Strang, King’s College, Lon-
don, presented new research into
how to manage cases of opioid over-
dose, while encouraging psychia-
trists to stand up to the public and
policymakers in defence of their
patients’ needs.
‘We need to get politicians and
the general public to grasp that
they should put away their moralis-
ing and look at what the actual level
of human suffering is around this,’
stated Professor Sir John Strang.
‘For about a decade now, drug over-
doses far exceed deaths caused by
road traffic accidents in both the
USA and UK.’
The first step is to know when to
target preventative interventions.
Opioid overdose deaths do not
occur randomly but can be pin-
pointed around an individual being
32 I Progress in Neurology and Psychiatry I Vol. 23 Iss. 2 2019
‘The friends and family actually do
a lot of interventions and the only
issue is that they haven’t been told
18 th Latest Advances in Psychiatry Symposium
Mental health after Brexit? From psychosis to borderline personality disorders
what the right ones would be,’ said
Sir John Strang. ‘In such cases, take-
home naloxone should be consid-
ered in the same way as an EpiPen.’
The standard mode of adminis-
tration for naloxone is intrave-
nously (IV) but, in an effort to make
it more accessible, Sir John Strang
released from prison or coming out worked with a team to produce an
of rehab, for example. Data show intranasal version that was com-
that 1 in 200 people with prior drug pared with iv and intramuscular
abuse history are dead within a fort- (IM) versions.2 Results showed that
night of their release from prison, IV administration of naloxone
the vast majority from drug-related (0.4mg) produces a ‘big spike’ in
causes. ‘Until around 2000 we were mean plasma concentration, throw-
unaware that there was this time of ing the patient immediately into
such intense risk,’ said Professor withdrawal symptoms, which is why
Sir John Strang, ‘which is a failing ambulance crews now administer
of the way we don’t use different IM naloxone (0.4mg) to avoid an
data sets’. aggressive spike but ensure similar
There is also an increased risk of recovery. The onset of action of
overdose in patients that either are intranasal naloxone at a 1mg dose
starting, or completing, a treatment was not immediate enough for use
course involving opioids. For exam- in the emergency care setting, while
ple, there is an excess mortality in the 4mg intranasal dose produced
patients during the first month of a ‘big spike’ in mean plasma con-
methadone treatment that reoccurs centration that resulted in with-
at treatment cessation.1 After the drawal symptoms. Instead, the 2mg
first month of treatment there is a intranasal naloxone dose showed
fivefold reduced mortality rate, the best speed of onset compared
however, so it is still a very effective with increased mean plasma con-
treatment for addiction, but clini- centration, hence why it has now
cians should be aware of the points been accepted in Europe.
at which their patients will be par- However, as the nasal spray was
ticularly vulnerable. tested in people with healthy nasal
In cases when overdose has mucosa it may be problematic in
occurred, novel ways to resuscitate long-term drug users, or people
patients can help reduce fatalities. with colds and/or allergic rhinitis.
Naloxone is an effective treatment Instead, ‘we have been looking at
for opioid overdose, and the fact developing a rapid-absorption,
that many overdoses occur in the instant-melt tablet of naloxone that
presence of others presents options is currently in progress and looks
for an early treatment response. quite promising,’ concluded Sir
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John Strang. ‘Making naloxone
much more accessible and much
more portable is crucial.’
The future of neurosurgery for
severe mental illness
In her presentation, Professor
Eileen Joyce, University College
London, treated delegates to the
grisly history of neurological sur-
gery for mental illness to demon-
strate how the process has refined
and developed to now offer hope
for patients with treatment-resistant
depression (TRD) and obsessive
compulsive disorder (OCD).
‘Personally, I think that external
brain stimulation is the way to go,’
said Professor Joyce. ‘Neurological
surgery techniques are still availa-
ble on the NHS but they are tightly
regulated and will only ever be
available for the very few. Currently,
new techniques are being devel-
oped that are still ablation but
mean patients don’t have to go
through an operation.’
Anterior capsulotomy and ante-
rior cingulotomy are the neurosur-
gical options currently available on
the NHS for OCD and TRD. In the
procedure, tissue is ablated using
knife cuts or radiofrequency ther-
mocoagulation. Results show that in
severe OCD 54% of patients under-
going anterior capsulotomy
achieved full response according to
the Yale-Brown Obsessive Compul-
sive Scale (YBOCS),3 with 54% of
patients with TRD also having a full
response. 4 Adverse side-effects
included urinary incontinence,
weight gain and lethargy, ‘so this is
only for patients with severe men-
tal illness who have not responded
to multiple courses of different
medication combinations and cog-
nitive behavioural therapy,’ said
Professor Joyce.
However, less invasive ablation
techniques for OCD are being
developed. For example, the
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MRI-guided gamma knife cap-
sulotomy (MRIGKC) targets a
high-energy radioactive emitting
isotope 60 Co at the part of the
brain that needs to be ablated,
while the MRI-guided focussed
ultrasound capsulotomy (MRI-
FUC) delivers focussed ultra-
sound through a helmet onto the
area for ablation. Results show
that for MRIGKC, 56% of patients
(31/55) had an improvement in
the primary efficacy measure, but
side-effects included oedema, radi-
ation necrosis-induced cysts and
frontal lobe syndrome. MRIFUC is
thought to be a safer procedure,
with 55% of OCD patients (6/11)
shown to be full responders in a 24
month follow up.5
Deep brain stimulation (DBS) is
another option for patients with
severe OCD and, in contrast to abla-
tion, it is reversible (it can be turned
off and the device removed). In
patients with OCD, DBS in areas of the
anterior capsulotomy resulted in 62%
of participants having a full response,
sustained over three years.6 ‘Who
knows what will happen in the future
though?’ asked Professor Joyce. ‘DBS
may go out of fashion as it is very
labour intensive, while ablation tech-
niques might get more refined.’
DBS is not suitable for patients
with TRD. ‘It could be that the sub-
cortical circuitry that we know is
abnormal in depression is too wide-
spread, so targeting one small bit of
the circuitry may not be effective
enough,’ said Professor Joyce.
Instead, external brain stimula-
tion is a novel option being trialled
for treatment of depression. The
procedure, known as transcranial
magnetic stimulation (TMS), uses a
high frequency magnetic pulse to
induce an electric current flow in
neurons in the left dorsolateral pre-
frontal cortex, which is known to
connect to most of the neuro-net-
works thought to be abnormal in
Progress in Neurology and Psychiatry I Vol. 23 Iss. 2 2019 I 33
18th LAP symposium I Conference report
depression. ‘The effect size has been
small to medium, but actually there
have been highly significant clinical
outcomes,’ said Professor Joyce. The
barriers to implementation are how
labour intensive DBS is (patients
require 40 minutes of treatment
every day for four to six weeks). ‘In
the future, things will change,’ said
Professor Joyce. ‘Already, using an
intermittent theta burst TMS proto-
col has shortened the sessions from
37 minutes to 3.’ Other options
include having more sessions in
one day to shorten treatment dura-
tion, and home TMS systems to save
patient travel.
Severe personality disorder:
what not to do
In 2008, the first NICE guidance on
personality disorders did not rec-
ommend pharmacological treat-
ment on the basis that more
evidence was required. In his pres-
entation, Professor Mike Crawford,
Imperial College, London, brought
delegates up to speed with what the
evidence now tells us.
‘Despite the NICE guidance not
recommending it, we know that two
thirds of people with a diagnosis of
personality disorder in the UK are
taking long-term antidepressants,
despite no evidence of any benefit;
while 40% have been taking long-
term antipsychotic medication,’
said Professor Crawford.
Antidepressants are not effective
in treating symptoms of borderline or
other personality disorder, even in
cases when personality problems are
comorbid with depression.7 ‘We don’t
know why this happens,’ said Profes-
sor Crawford. ‘So not only do the anti-
depressants not work, but even if you
have depression and personality disor-
der the drugs seem to be ineffective.’
The quality of evidence investigat-
ing the efficacy of antipsychotic medi-
cation in patients with personality
disorders is currently poor; being
Conference report I 18th LAP symposium
short term, with no clear primary out-
come and a high attrition rate (nearly
50% are not followed up). At 12
weeks, the highest quality trial to
date found no significant improve-
ment in mental health in patients
with borderline personality disor-
der (BPD) treated with olanzapine,
but they had put weight on!8 Clo-
zapine, on the other hand, has been
shown to have some benefit in
patients with emotionally unstable
personality disorder, and a large
randomised trail is about to begin
on its efficacy in patients with BPD.
The potential of mood stabilis-
ers to treat BPD proved similarly
uninspiring. A large placebo-con-
trolled trial investigated the effi-
cacy of lamotrigine (400mg) in
patients with BPD. 9 ‘Results
showed that lamotrigine, given to
people with BPD, results in consid-
erable reduction in symptoms over
12 weeks – which is sustained – but
placebo has exactly the same bene-
fit!’ said Professor Crawford. ‘You
really couldn’t get less evidence of
the impact of a drug.’
Results from research into psy-
chological interventions for BPD
are sporadic. ‘They all make claims
that the active treatment is worth
doing,’ pointed out Professor Craw-
ford. ‘Yet I find it astonishing that
even in trials that show clear evi-
dence of harm in psychological
treatment they are able to say these
interventions have advantages.’
Dialectical behaviour therapy
(DBT) and mentalisation-based
therapy (MBT) are an exception
to this, with both showing efficacy
superior to other psychological
interventions, including cogni-
tive behavioural therapy. ‘One
possible reason is that DBT and
MBT are both based on groups –
it is about getting people with
interpersonal problems to learn
from each other,’ proposed Pro-
fessor Crawford.
34 I Progress in Neurology and Psychiatry I Vol. 23 Iss. 2 2019
However, DBT and MBT are
time intensive, so few people
receive them, and they have a high
drop-out rate. ‘There is therefore a
need to think again about low-in-
tensity interventions,’ Professor
Crawford said. Novel low-intensity
options currently being considered
include web-based psychoeduca-
tion, peer support groups and short
forms of DBT and MBT that would
last 12 weeks rather than 12 months.
Currently though, most
patients with personality disorders
receive ‘usual care’, which is spo-
radic and often even leaves
patients with worse problems to
do with their condition than when
they started treatment.10 ‘We need
to avoid misdiagnosis, overmedi-
cation and stand-alone psycholog-
ical treatments,’ said Professor
Crawford. ‘Instead, we need to
facilitate the use of evidence-based
treatments and ensure treatment
is given out by a thoughtful and
coordinated team.’
Mental health and wellbeing
among medical students and
doctors
Increased workload, staff shortages
and cases of litigation are all factors
straining the NHS and having a dev-
astating impact on the mental
health of its doctors. In his pres-
entation, Professor Dinesh Bhugra,
Kings College, London, outlined
the current situation and what doc-
tors can do to protect themselves.
‘An important question to ask is
if this is a new phenomenon?’ started
Professor Bhugra. Being a doctor
requires dealing with physical and
emotional distress in patients while
working long hours, often in isola-
tion. The personality traits of doc-
tors, as a group, also tend towards
high standards of professionalism
and resultant self-criticism. ‘These
are socially valuable traits but per-
sonally destructive,’ said Professor
Bhugra, as ‘in circumstances you
can’t control you feel trapped,
depressed and fed-up.’
A GMC report, 11 published in
2018, showed that nearly a quarter
(24%) of doctors in training had
suffered burnout to a high or very
high degree due to work, while
BMA counselling services receive
over 3000 calls from doctors per
year. Specialty-wide differences
show that psychiatry has the highest
rates of burnout and depression.
But what is driving the change?
Increasing workload and staff short-
ages are a big problem. The UK, for
example, has fewer doctors per per-
son than other leading European
economies, while a third of GP part-
ners are unable to fill vacancies.
‘This disparity is only going to
increase,’ warned Professor Bhu-
gra. As a result, nearly half of medi-
cal trainees (48%) reported that
they work in excess of their rostered
hours on a daily or weekly basis,
while a third of trainees said they
are always or often exhausted at the
thought of another shift.11
‘We all assume that as we are
doctors we can do everything, but
we can’t,’ Professor Bhugra
reminded the audience. ‘What is
really worrying is that only one-in-
three doctors admit to seeing their
GP if they feel unwell, with more
than a third reporting that they
self-prescribe to cope with work and
ill health.’
Work stressors are also making
the job even harder. For example,
the number of available mental
health beds has seen a 44%
decrease since 2000/1, while
cases of litigation against doctors
have doubled in the last 10 years.
The IMPACT trial showed that
doctors with a current complaint
against them were almost twice as
likely to suffer moderate-to-se-
vere depression than colleagues
with no complaints.12
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Health Education England has
published guidelines to help; how-
ever, ‘their solutions are completely
bizarre,’ said Professor Bhugra.
‘Instead, if we are going to deal with
stress and burnout we need to focus
on the individual AND the system.
First and foremost, you need to be
aware of your own health and well-
being. Seek help early, share prob-
lems, admit vulnerability: you are
human just like your patients.’
Generalised anxiety disorder:
new insights into aetiology and
treatment
Generalised anxiety disorder
(GAD) is a common psychiatric
condition about which relatively lit-
tle is known. In his presentation,
Professor David Baldwin, University
of Southampton, informed dele-
gates about new research into the
aetiology of GAD as an autoim-
mune disorder, along with the novel
treatment options.
‘A significant number of GAD
patients don’t respond to treatment
and those that do can sometimes
relapse and/or experience distress-
ing adverse events,’ said Professor
Baldwin. ‘We want treatments with
an early onset of effect and with
greater efficacy, so there is much
room for improvement in the devel-
opment of a new anxiolytic drug.
‘As in the current research on
depression, there is a lot of new
data from small studies suggesting
anxiety disorders like GAD are asso-
ciated with deficiencies, or low lev-
els, of anti-inflammatory cytokines
and higher levels of pro-inflamma-
tory cytokines,’ said Professor Bald-
win. ‘So, a tempting hypothesis
would be to take an anti-inflamma-
tory drug and see if it had anxiolytic
potential in GAD.’ Carbon dioxide
(CO 2 ) is a useful experimental
medicine method to test the effi-
cacy of potential treatments. A brief
inhalation of air with a 35% CO2
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concentration can reliably induce
acute severe anxiety in patients with
a panic disorder, while a lower dose
of 7.5% CO2 concentration, inhaled
over 20 minutes, can produce fea-
tures that resemble GAD.
Using this model, patient
responses to duloxetine, meman-
tine, quetiapine, ibuprofen and
amiloride were monitored. Results
showed that duloxetine reduced
subjective anxiety independent of
effects on autonomic function;13
memantine, on the other hand, had
no significant effect on subjective
anxiety;14 while quetiapine reduced
CO2-induced anxiety on some meas-
ures but had no effect on auto-
nomic or neurocognitive
measures.15
Interestingly, ibuprofen was
associated with anxiolytic effects in
patients with GAD when compared
with placebo by attenuating the sub-
jective anxiety response of patients
without a significant difference in
autonomic response or attention
control.16 ‘So, you can see how this
would link to the idea of repurpos-
ing NSAIDs as potential anxiolyt-
ics,’ said Professor Baldwin.
Amiloride (a non-specific
acid-sensing ion channel blocker)
reduced subjective anxiety com-
pared with placebo (p=0.083)17 ‘and
we are still exploring its autonomic
and neurocognitive effects’, fin-
ished Professor Baldwin. ‘New
developments are costly and there
have been a lot of late-stage failures
– so repurposing existing treat-
ments might be beneficial.’
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