Neal C M Hattersley Lynne M Drummond

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Transcript Neal C M Hattersley Lynne M Drummond

What’s New in OCD????
Lynne M Drummond
Copyright L M Drummond
Firstly, what do we know about OCD ??
• Tends to run in families and does have a genetic
component (but not a simple
transmission....multifactorial)
• Responds to a psychological treatment (CBT)
involving Graded Exposure and Response
Prevention (ERP)
• Responds to treatment with drugs acting on the
neurotransmitter (messenger), SEROTONIN
....(Serotonin Reuptake Inhibitors = Clomipramine or
one of the SSRIs)
Copyright L M Drummond
SO........
• Approximately 2/3rds of people with
clinical OCD will respond to ERP alone
• Approximately 60% of people with OCD
will respond to treatment with SRIs (but
some people will respond to one drug
and not another...ie if one doesn’t work,
it is worth switching to another
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ACTION OF THE SRIs
Fronto-SeptoHippocampal
Circuits
LACK of
SEROTONIN IN OCD
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Serotonin Reuptake Inhibiting (SRI)
drugs
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CLOMIPRAMINE (225mg/day)
FLUVOXAMINE (300mg/day)
PAROXETINE (60mg)
FLUOXETINE (60mg)
SERTRALINE (200mg)
(CITALOPRAM and ESCITALOPRAM)
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Despite this some people still do
not respond to SRIs or ERP
Fronto-SeptoHippocampal
Circuits
LACK of
SEROTONIN IN
OCD
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Basal
ganglia
circuits.
Mediated by
DOPAMINE
Efficacy of augmentation for OCD
with Dopamine Blockers
• Overall only 1/3 of SRI refractory
patients improve with addition of
Dopamine Blockade (Bloch et al 2010).
• Most of the studies are small but some
better evidence for rispiridone than
others
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HOWEVER!!!!
• Remember that adding ERP to the SRI
is MORE EFFECTIVE than drug
augmentation
• Cognitive-behavioral therapy vs rispiridone for augmenting SRIs
in OCD: a randomised controlled trial.Simpson HB et al.
(2013)JAMA Psychiatry. Nov;70(11):1190-9.
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HIGH DOSE SSRIs in REFRACTORY OCD
HIGH DOSE SSRIs in REFRACTORY OCD
• Mostly open label studies have shown beneficial
effect
• A double-blind (non-placebo-controlled trial) of
sertraline showed greater symptom reduction
between 200mg -400mg. (Ninan et al., 2006)
• Retrospective naturalistic survey suggested high
dose SSRI is associated with clinical improvement
and well tolerated in treatment resistant patients
(Pamploni et al., 2009)
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Recent Research....
GLUTAMATERGIC SYSTEM
• Concentrating on Glutamate Metabolism
• Glutamate and cellular transmission is a
highly complex system.
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..................
Glutamate modulates
Neurotransmitters
Glial
Cell
Glutamate
Neurone
Neurone
.................
.................
Neurotransmitters (eg
serotonin
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Recent Research....GLUTAMATE
• Agents which are being explored include:– Ketamine
– Topiramate
– N-Acetyl-Cysteine
– Riluzole
– Memantine
– Glycine
– Sarcosine (N-methyl glycine)
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Recent Research....GLUTAMATE
• Agents which are being explored include:– Gabapentin
– Amantadine
– D-Cycloserine
– Acamprosate
– PREGABALIN
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What about other therapies for
OCD?
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Deep Brain Stimulation
• Approx. 58 patients with
“severe” OCD have had DBS
treatment in Continental
Europe and North America.
• 2/3 have a significant
response (using 35%
reduction as criteria)
• One ongoing trial in
UK...with patients who have
failed all other reasonable
medication and extensive
CBT
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Collaborators
• Psychiatrists (UCH;UCL;SGUL/SWLSTG;University of
Dundee;HertsParts ; University of Herts)
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Prof Eileen Joyce
Dr Lynne M Drummond
Prof Naomi Fineberg
Prof Keith Matthews
Dr Tyagi (Research Registrar)
• Neurosurgeons (UCH/UCL)
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Prof Marwan Hafiz
Mr Zrinzo
• Cognitive Neuroscientists (University of Cambridge)
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Prof Trevor Robbins
Prof Barbara Sahakian
• Neurologists (UCH/UCL)
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Dr Foltynie
Dr Limousin
Deep Brain Stimulation
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Transmagnetic Cranial
Stimulation
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Transcranial Magnetic
Stimulation
• Has been performed in US and Europe
• Studies all involve small numbers so far
• No studies in the UK (but one being planned)
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OXYTOCIN, GENES and OCD
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OXYTOCIN
• Oxytocin is a hormone released in the
brain when an individual feels loved and
cared for.
• It is released by mothers when cuddling
their babies
• It is also released when we are happy
and content
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GENES AND OCD
• We know OCD runs in families
• However, having a parent with OCD is
not guarantee of your getting OCD or
vice versa
• Thus OCD is “multifactorial” in origin
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Future Directions of Oxytocin
Research??
• We know that many genes can be modified by
environment.
• Is it Oxytocin which can bind to the genes and make
them less likely to be active??
• I.e. is Oxytocin the secret to nurturing being a
partially protective factor for some people genetically
predisposed to OCD???
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Inflammation and OCD
Copyright L M Drummond
Inflammation and OCD
• This has been researched for many
years
• Firstly with the concept of PANDAS
• More recently this has been broadened
(although still controversial) and more
discussion about PANs
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Immunological Processes and
OCD
• Similarity between childhood OCD and OCD
symptoms in Sydenham’s Chorea
• PANDAS
– Paediatric
– Autoimmune
– Neuropsychiatric
– Disorders
– Associated with
– Streptococci
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OCD and Steptococci – study of 96
patients
Copyright L.M. Drummond
•
NICHOLSON,TRJ., FERDINANADO,S,
KRISHNAIAH,RB, ANHOURY,S.,
LENNOX., McKENNA, P., MATAIXCOLS, D., CLEARE,A., VEALE,D.,
DRUMMOND,LM., FINEBERG,NA.,
CHURCH,A., GIOVANNONI,G. and
HEYMAN, I.
•
Increased prevalence of
antibasal ganglia antibodies
in adult obsessivecompulsive disorder: a
cross-sectional study
•
British Journal of Psychiatry, (2012)
200:381-386
96 Adult Patients with severe OCD were
compared with a general psychiatric control :
• Presence anti-streptolysin-O titres (ASOT)
and of antibasal ganglia antibodies (ABGA)
recorded
• Positivity for ABGA was observed in 19/96
(19.8%) OCD patients compared with 2/50
(4%) of controls (Fisher’s exact p=0.012).
• ASOT positivity was not associated with
ABGA positivity and was not raised in OCD
subjects
Copyright Lynne M Drummond
ABGA Positivity
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OCD and Bacterial Infection
• Appears streptococci MAY have a part
to play in precipitating OCD in some
patients.
• The patients in whom raised antibodies
in the brain are found are more likely to
have other more “neurological” signs
Copyright Lynne M Drummond
Recent Research in US
concentrating on the Microbiome
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Microbiome Theories
• There has been a dramatic increase in recent
years of immune disorders such as ASTHMA
and ECZEMA
• Theory that this may be a result of lack of
exposure of children to as many bacteria in
childhood.e.g less playing with livestock etc.
• Also noted that AUTISM diagnosis has
increased? Related to above???
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Microbiome Theories
• This lack of exposure to “dirt and
germs” in childhood means we develop
“leaky gut walls” which makes us more
prone to inflammatory diseases.
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Microbiome Research
• Current research examining possible links
with the Microbiome and abnormal allergic
responses in OCD ( particularly those linked
to autism)
Copyright L M Drummond
..................
Glutamate modulates
Neurotransmitters
Glial
Cell
Glial
Cell
Neurone
Neurone
.................
.................
Neurotransmitters (eg
serotonin
Copyright L M Drummond
Microbiome Research
• In US they are thinking about gut flora
(? Faecal transplant) and other
treatment s aimed at reducing brain
inflammatory reactions (pig tape-worm
ova).
Copyright L M Drummond
Summary
• Most people with OCD will respond to either:
– SRI drugs
– CBT involving ERP
• Some people fail to respond to standard treatments and may
require:
– Addition of a dopamine blocker
– Above normal doses of SSRIs
• New treatments being examined include:
– The role of drugs acting on Glutamate
– DBS
– TcMS
Copyright L M Drummond
Summary
• New Theories about Genetics and the possible role of Oxytocin
in modifying genes
• New theories about Inflammation and OCD include:
– Furthering to work of PANDAS
– Looking at the possible role of allergy
– Looking at the possible role of the Microbiome
Copyright L M Drummond
Any Questions??????