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
Copyright L M Drummond
ACTION OF THE SRIs
Fronto-SeptoHippocampal
Circuits
LACK of
SEROTONIN IN OCD
Copyright L M Drummond
Serotonin Reuptake Inhibiting (SRI)
drugs
•
•
•
•
•
•
CLOMIPRAMINE (225mg/day)
FLUVOXAMINE (300mg/day)
PAROXETINE (60mg)
FLUOXETINE (60mg)
SERTRALINE (200mg)
(CITALOPRAM and ESCITALOPRAM)
Copyright L M Drummond
Despite this some people still do
not respond to SRIs or ERP
Fronto-SeptoHippocampal
Circuits
LACK of
SEROTONIN IN
OCD
Copyright L M Drummond
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
Copyright L M Drummond
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.
Copyright L M Drummond
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.
Copyright L M Drummond
..................
Glutamate modulates
Neurotransmitters
Glial
Cell
Glutamate
Neurone
Neurone
.................
.................
Neurotransmitters (eg
serotonin
Copyright L M Drummond
Recent Research....GLUTAMATE
• Agents which are being explored include:– Ketamine
– Topiramate
– N-Acetyl-Cysteine
– Riluzole
– Memantine
– Glycine
– Sarcosine (N-methyl glycine)
Copyright L M Drummond
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
Copyright L M Drummond
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)
–
–
Prof Marwan Hafiz
Mr Zrinzo
• Cognitive Neuroscientists (University of Cambridge)
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–
Prof Trevor Robbins
Prof Barbara Sahakian
• Neurologists (UCH/UCL)
–
–
Copyright L M Drummond
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
Copyright L M Drummond
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
Copyright L M Drummond
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
Copyright L M Drummond
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???
Copyright L M Drummond
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
Copyright L.M. Drummond
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
Copyright L M Drummond
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??????