what’s new in ocd???? lynne m drummond copyright l 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)


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


ACTION OF THE SRIs

Fronto-Septo-Hippocampal CircuitsLACK of SEROTONIN IN OCD


Serotonin Reuptake Inhibiting (SRI) drugs

• CLOMIPRAMINE (225mg/day)

• FLUVOXAMINE (300mg/day)

• PAROXETINE (60mg)

• FLUOXETINE (60mg)

• SERTRALINE (200mg)

• (CITALOPRAM and ESCITALOPRAM)


Despite this some people still do not respond to SRIs or ERP

Fronto-Septo-Hippocampal CircuitsLACK of SEROTONIN IN OCD

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


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.


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)


Recent Research....GLUTAMATERGIC SYSTEM

• Concentrating on Glutamate Metabolism• Glutamate and cellular transmission is a

highly complex system.


Glutamate modulates Neurotransmitters

..................

.................

.................

Neurotransmitters (eg serotonin

NeuroneNeurone

Glial Cell

Glutamate


Recent Research....GLUTAMATE

• Agents which are being explored include:-– Ketamine– Topiramate– N-Acetyl-Cysteine– Riluzole– Memantine – Glycine– Sarcosine (N-methyl glycine)


Recent Research....GLUTAMATE

• Agents which are being explored include:-– Gabapentin– Amantadine– D-Cycloserine– Acamprosate– PREGABALIN


What about other therapies for OCD?


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 CBTCopyright L M Drummond

Collaborators

• Psychiatrists (UCH;UCL;SGUL/SWLSTG;University of Dundee;HertsParts ; University of Herts)

– 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)– Prof Trevor Robbins– Prof Barbara Sahakian

• Neurologists (UCH/UCL)– Dr Foltynie– Dr LimousinCopyright L M Drummond

Deep Brain Stimulation


Transmagnetic Cranial Stimulation


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)Copyright L M Drummond

OXYTOCIN, GENES and OCD


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


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


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???


Inflammation and OCD


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


Immunological Processes and OCD• Similarity between childhood OCD and OCD

symptoms in Sydenham’s Chorea• PANDAS

– Paediatric– Autoimmune – Neuropsychiatric– Disorders– Associated with– Streptococci


OCD and Steptococci – study of 96 patients

• NICHOLSON,TRJ., FERDINANADO,S, KRISHNAIAH,RB, ANHOURY,S., LENNOX., McKENNA, P., MATAIX-COLS, D., CLEARE,A., VEALE,D., DRUMMOND,LM., FINEBERG,NA., CHURCH,A., GIOVANNONI,G. and HEYMAN, I.

• Increased prevalence of antibasal ganglia antibodies in adult obsessive-compulsive disorder: a cross-sectional study

• British Journal of Psychiatry, (2012) 200:381-386

Copyright L.M. Drummond

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


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???


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.


Microbiome Research

• Current research examining possible links with the Microbiome and abnormal allergic responses in OCD ( particularly those linked to autism)


Glutamate modulates Neurotransmitters

..................

.................

.................

Neurotransmitters (eg serotonin

NeuroneNeurone

Glial Cell

Glial Cell


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).


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


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


Any Questions??????

what’s new in ocd???? lynne m drummond copyright l m drummond

Documents

drummond slide

drummond copyright

ocd copyright

refractory ocd slide

dopamine copyright

ssris copyright

escitalopram copyright

clinical ocd