Ocd santhosh final
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This document summarizes the biological treatments for obsessive compulsive disorder (OCD) according to the DSM-5 criteria. It discusses the neurobiology of OCD including structural changes in the brain, functional studies showing increased activity in certain areas, and neurotransmitter imbalances. FDA approved medications for OCD like SSRIs and clomipramine are outlined. Augmentation strategies and treatments for resistant cases are provided. Other somatic therapies explored include repetitive transcranial magnetic stimulation, deep brain stimulation, electroconvulsive therapy, and vagus nerve stimulation. Neurosurgical procedures are discussed as last line treatments for severe, long-standing OCD.
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Ocd santhosh final
- 1. Biological treatments of OCD Dr.S.Santhosh Goud Chairperson;Dr.Ravi Awchar
- 2. DSM 5-OCD and related disorders • OCD • BDD • Hoarding disorder • Trichitillo mania/HPD • Excoriation/skin picking disorder • Substance/medication induced OCD • OCD due to another medical condition
- 3. Ocd criteria DSM 5 criteria • Presence of obsession/compulsion • Time consumption>1 hr/clinically significant distress or impairment • Rule out role of substance/other medical condition • Not due to other mental disorder
- 4. • Obsessions are persistent, uncontrollable thoughts, impulses, or images that are intrusive, unwanted and disturbing. They cause anxiety or discomfort that significantly interferes with normal life • Individuals who have OCD feel compelled to perform repetitive actions called compulsions, or rituals, in an attempt to relieve the distress caused by the obsessions
- 5. Neuro biology of OCD Emotional brain controls the reasoning brain The part of the brain responsible for ocd, functions very much on the same emotional level as that of a two year old. Reasoned argument is, therefore, pointless…!
- 6. Loss of filtering • Thalamus-sensory gating • Caudate nuleus-thought filtering
- 7. • Orbito frontal cortex-combines thoughts and emotions • Cingulate gyrus in the middle of brain • Helps in shifting attention from one thought/behavior to another • CG also acts as a signaling center for danger so forces to do compulsion
- 9. Structural changes • Volume reduction of the OFC • Cingulate cortex • Decreased OFC with increased thalamic volume constant finding in refractory cases
- 10. Functional studies • FDG-PET increased glucose metabolism in ofc,caudate,thalamus,pfc and acc
- 11. Neurotransmitter changes • Serotonin • Autoreceptors (5HT1D) require higher SSRI dose • Role of 5HT 7 receptors Dopamine • Quinpirole treated rats-compulsive checking
- 12. Glutamate • OCD is a hyperglutaminergic state of prefrontal brain-(Carlsson) • SSRI, Clomipramine do regulate this Glutamate regulators used in resistant cases
- 13. Neuroimmunology • Auto immunity to basal ganglia • Sydenham chorea, PANDAS • D8/17 B lymphocyte antigen more prone • Plasmapheresis, iv immunogloblin useful
- 14. Genetics • Higher concordance in monozygotic twins • 5HTTLPR • Role of DRD4 variant • COMT variation • polymorphisms of MAOA genes
- 15. Course and prognosis • Adolescent onset~65% • <15% after 35 yrs of age • Nearly 70 percent of patients report a continuous course of symptoms, and 23 percent experience a waxing and waning course • Average time to treatment after meeting diagnostic criteria for OCD is 11 years (The Brown Longitudinal Obsessive
- 16. Naturalistic follow up studies from pre-sri/cbt era • Improvement in 66% recovery in 32% (lewis,1936) Pollitt study-101 patients • 3 months-15yrs(mean 3.4yrs) out come • 34 leucotomized • 67 non leucotomized • 40% good response;most of them with in 2 years • Most of the patients having waxing waning
- 17. • Skoog &skoog study 1999 • 250 patients admitted between 1947-1953 • Reexamined between 1989-1993 • 75 died,32 lost follow up • 144 patients data could be collected • Shneiders ocd criteria
- 18. • Improvement in 83% • Recovery 48% • Complete recovery 20% subclinical symptoms 28% • 38% recovered in first decade • Hal of them had illness for >30yrs
- 19. Recent studies • Full remission 20-45%(Y-BOCS <3) • Partial remission 20-55%( 4-14) • Clinical ocd10-60%(>15)
- 20. • 40-60% unsatisfactory response • Predictors of treatment response..?
- 21. • Hoarding disorder poor response to SSRI • High scores on sexual/religious obsessions poor response to SRI/CBT(Matix-colas et al) • Somatic obsessions had poorer insight and less response to drugs(expect MAO-I)
- 23. FDA approved drugs • Anafranil (clomipramine)-c10 • Prozac (fluoxetine)-c7 • Luvox (fluvoxamine)-c8 • Paxil (paroxetine hydrochloride) • Zoloft (sertraline)-c6
- 24. “Off-label" OCD medications • Celexa (citalopram) • Lexapro (escitalopram) • Effexor (venlafaxine) • Cymbalta (duloxetine) • Remeron (mirtazapine)
- 25. Augmenting agents • Antipsychotic medications(Risperdal (risperidone)Zyprexa (olanzapine)Seroquel (quetiapine)) • Other augmenting agents • B blocker • 5HT1 agonist • Ondansetron • Riluzole • Memantine
- 26. How to choose the right drug • Diagnosis;severity;comorbid illness • Medical history;the potential side effects of each medication, and the possibility of an adverse interaction with another drug the person is taking
- 27. drug Starting dose Target dose(mg/day ) Usual Maximum dose Occassional max dose Fluoxetine 20 40-60 80 120 Sertraline 50 200 200 400 Fluvoxamine 50 200 300 450 Paroxetine 20 40-60 60 100 escitalopram 10 20 40 60 clomipramine 25 100-250 300
- 28. Resistence vs refractoriness • Rauch and Jenike, in 1994, established the difference between "resistant" and "refractory" patients. • They defined as "resistant" those who participate in a trial with any first-line therapy and do not have a satisfactory response, while the "refractory" patients are those who do not respond appropriately to several treatments administered in an adequate manner
- 29. • Pallanti et al • No response -<25% reduction in YBOCS score CGI-I 4 • Refractory- failure to respond to all available treatments • Pseudo resistance..?
- 30. Predictors of treatment non-response • Early age of onset • Longer ocd • Mixed ocd • Sexual obsessions • Washing compulsons • Hoarding • Poor insight • Schizotypal pd
- 31. • Switching to another SSRI(~50%) • Switch to Clomipramine(upto300mg) (min 2 SSRI trails;NIMHANS ocd clinic) • IV Clomipramine (~43%) • Min 14 infusions • 250mg/day • More side effects
- 32. • SSRI to venlafaxine or Mirtazepine Augmentation • Best evidence with Risperidone(0.5-6mg) • First doc for augmentation • Other drugs haloperidol(1.5- 5mg),olanzepine(2.5-20),quetiapine(50- 300) • Clonazepam(upto 6.5mg) • Buspirone(60-90mg),
- 33. • Nicotine,cbzp,lamotrigene,gabapentine, reboxetine,psychostimulants,nac, Aripiprazole less evidence • Lithium, thyroid,l-tryptophan(2gm) ineffective;useful for comorbidities • once-weekly oral morphine sulfate • Other less well-supported monotherapies include dextroamphetamine (Dextrostat), tramadol (Ultram), monoamine oxidase inhibitors, ondansetron (Zofran)
- 34. • When to change augmentation? • no desired response by 6-8wks • Augmentation for how long?
- 35. Combination strategies • SSRI and clomipramine • Superior to switching(Pallanti et al) • Look for serotonin syndrome
- 36. Intensive residential therapy • IP treatment • Multidisciplinary approach • Pharmacotherapy • Daily CBT 2-4 hours • Group therapy
- 39. Other somatic therapies • r-TMS • DBS • ECT • Vagal stimulation
- 40. r-TMS • Since 1997, in published trials, a total of 110 OCD patients have been treated with rTMS • Greenberg et al.inhibition of the prefrontal activity with rTMS might reduce obsessive-compulsive symptoms.
- 41. • 1) stimulation of the dorsolateral prefrontal cortex (DLPFC) • 2) inhibition of the orbitofrontal cortex (OFC) directly • 3) inhibition of the supplementary motor area (SMA).
- 42. Deep brain stimulation • Nucleus accumbens • Anterior capsule • Caudate nucleus • Subthalamic nucleus
- 43. ECT • The primary indication would be the severe depression with which intractable OCD is often associated(Bulletin of Clinical Psychopharmacology • ECT Use in Refractory Obsessive-Compulsive Disorder Nesrin B. Tomruk Omer Saatcioglu)
- 45. Neurosurgical procedures Criteria • Diagnosis by standard criteria • Severe ocd • Long standing(>5 yrs) • At least 3 serotenergic(one should be clomipramine),2 augmenting agents, for 12 weeks • Adequate cbt (20hrs) • Less than 25% improvement with treatment
- 46. Procedures • Anterior capsulotomy • Anterior cingulotomy • Subcaudate tractotomy • Limbic leukotomy(subcaudate tractotomy with anterior cingulotomy) Gamma knife capsulotomy safer and non- invasive
- 47. Further reading on psycho surgery in OCD • Indian J Psychiatry. 2009 Jul-Sep; 51(3): 216–221 Surgical treatment of obsessive compulsive disorders: Current status Paresh K. Doshi
Editor's Notes
- 4th most common psychiatric condition(phobias,substance use, mdd) prevalance1.9%-3.3%(~1.6)
- Dd-gad, bdd,hoardind,hair pilling,skin pricking,stereotypic movement disorder,eating disorder,addictive disorder,illness anxiety disorder,paraphilias,impulse control disorder,schiz,asd, ocpd
- the Thalmus processes sensory images coming to the brain from the rest of the body, while the Caudate Nucleus, part of the Basal Gangli in the centre of the brain controls and sorts sensory information and does thought filtering. When these messages are being misinterpreted, ‘misfiring’, the thinking part of the brain is naturally confused and is responding chemically to a threat perceived by the primitive, non-reasoning part of the brain with rational doubt of the threat’s danger, but a major need to response as if the danger is real. In effect, the Caudate Nucleus is letting unnecessary thoughts and impulses through to the Cortex where the thoughts and emotions combine; and an over active Cingulate Nucleus at the brain’s centre, which helps shift attention from one thought or behaviour to another, becomes over active and gets stuck on certain behaviours, thoughts or ideas. The Cingulate is that part of the brain which tells the OCD sufferer that something terrible will happen if the compulsions are not carried out.
- In ocd cd losts the filtering functions;allows unnecessary thoughts n urges works as a poor doorman There is a convergence of evidence implicating the corticostriatothalamocortical (CSTC) loop involving orbitofrontal (OFC) cortex, anterior cingulated cortex (ACC) and basal ganglia as central to the pathophysiology of OCD.[4–6] Two distinct routes are conceptualized from the striatum to the thalamus; the so-called “direct” and “indirect” pathways. The direct pathway projects from the cortex to the striatum to the internal segment of globus pallidus and substantia nigra to the thalamus and then back to the cortex. The indirect pathway is similar from the cortex to the striatum but then projects to the external segment of the globus pallidus to the subthalamic nucleus, before returning to the internal segment of the the globus pallidus/substantia nigra, there joining the direct pathway to the thalamus and projecting back to the cortex. Impulses transmitted via the direct pathway disinhibit the thalamus, presumably resulting in a release of behaviors as necessary for an adaptive function. Activity in the indirect pathway inhibits the thalamus, resulting in the cessation of ongoing behavioral routine. The prevailing theory on OCD suggests that a hitherto unknown primary striatal pathologic process underlies a relative imbalance favoring striatothalamic inhibition leading to hyperactivity within OFC and ACC, the caudate nucleus (CN) and the thalamus
- Ofc tells us when something is wrong an when something should be avoided like an early warning system In ocd it does overtime In ocd cg becomes overactive
- Volume reduction proportionate to severity of illness
- Ht7 antagonism results in decreased oc syptoms
- Glu regulators are topiramate,riluzole n d-cycloserine
- seretonin transporter gene(5httlpr)
- When the initial treatment is unsatisfactory, several factors may be contributing to the lack of improvement: interference by concomitant conditions, inadequate patient adherence to the treatment plan, the presence of psychosocial stressors, the family&apos;s degree of accommodation for the patient&apos;s symptoms, and the patient&apos;s inability to tolerate psychotherapy or medication.
- CMI was first used in 1968 by Reynghe de voxrie
- should all be considered when deciding which medication to use Y-BOCs, Maudsley oc inventory, brown assessment of beliefs, Responsibility attitude scale, CGI scale
- Some patients may need to start at one half of this dosage or less to minimize undesired side effects such as nausea or to accommodate anxiety about taking medication. CMI less than 150mg subtherapeutic These dosages are sometimes used for rapid metabolizers or for patients with no or mild side effects and inadequate therapeutic response after eight weeks or more at the usual maximal dosage. Combined plasma levels of clomipramine plus desmethylclomipramine 12 hours after dosing should be kept below 500 ng per mL to minimize risk of seizures and cardiac conduction delay. Sertraline is better absorbed with food
- Trd defined by thase n rush treat,ment guidelines for trd fleck and horwath- optimization of dose,switching to another first line approach,augmentation,combination
- One study had shon 76% benefit in ssri non-responsers But if the pt not responded to paroxetine then venlaf not useful
- Relapse rate of 83% with in first 2 months after stoppinh augmentation;so better to continue with primary drug
- Aim for clomipramine levels of 225-350 ng/ml and combined clomipramine and desmethylclomipramine levels of &lt; or = to 500 ng/ml in blood samples drawn about 12 hours after a dose; steady state takes two to three weeks to achieve
- Massachusetts irt study administered for 3 months 30% improvement in ybocs score
- They applied rTMS (80% motor threshold, 20 Hz for 2 s/min) for 20 min to 12 patients with OCD and found significantly decreased compulsive urges for 8 h after stimulation
- The SMA was chosen as a useful target for rTMS because it has extensive connections with regions implicated in cognitive processes and motor control
- ECT has occasionally been used for the treatment of anxiety disorders and currently no existing guideline considers anxiety disorders as a primary indication for ECT
- Kumud Chawla Gamma Knife Centre in India :The 1st Centre of Gamma Knife Radiosurgery In India