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Ocd a hidden_epidemic

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OCD overview

OCD overview

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  • Convergent evidence from functional and structural neuroimaging suggests that abnormalities in the circuitry interconnecting the cortex, basal ganglia, and thalamus. The canonical connections forming these cortico-striato-thalamo-cortical (CSTC) loops is shown in simplified form here. Projections in this circuit use both the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA, as shown. Modulatory dopamine critically modulates information flow through this circuit. Other important modulatory neurotransmitters, such as acetylcholine, serotonin, and histamine, are excluded for clarity.
  • Changes in vmPFC/OFC/dACC activity have been linked to fear conditioning and recall in normal subjects with vmPFC activity and structure particularly relevant for fear extinction recall. Overlap in the circuits associated with fear conditioning and OCD dysfunction suggests that these patients may be less flexible in adjusting adverse responses based on new information.Dysfunction of the vmPFC/OFC/dACC network may lead to an increase in incentive-based fear learning and habit formationPFC regions associated with OCD pathology are not only involved in aversive behaviors and avoidance; they also mediate reward processing. Indeed, OCD patients are also impaired on tasks using rewarding outcomes
  • Presentation of OCD symptoms is similar in children and adults.Younger children will not be able to recognize that their obsessions and compulsions are both unnecessary (e.g., you don’t really need to wash your hands) and extreme (e.g., washing hands for 15-20 s is fine, but 5 min in scalding water is too much) in nature.In young children, compulsions often occur without the patient being able to report their obsessions, while adolescents are often able to report multiple obsessions and compulsions. Children and adolescents are also more likely to include family members in their rituals and can be highly demanding of adherence to rituals and rules, leading to disruptive and oppositional behavior and even episodes of rage.Youth with OCD are generally more impaired than adults with the same type of symptoms
  • Presentation of OCD symptoms is similar in children and adults.Younger children will not be able to recognize that their obsessions and compulsions are both unnecessary (e.g., you don’t really need to wash your hands) and extreme (e.g., washing hands for 15-20 s is fine, but 5 min in scalding water is too much) in nature.In young children, compulsions often occur without the patient being able to report their obsessions, while adolescents are often able to report multiple obsessions and compulsions. Children and adolescents are also more likely to include family members in their rituals and can be highly demanding of adherence to rituals and rules, leading to disruptive and oppositional behavior and even episodes of rage.Youth with OCD are generally more impaired than adults with the same type of symptoms
  • OCS might manifest at different time points during the course of schizophrenia illness. In addition, the clinical course is highly variable. Blue symbols indicate the onset and severity of OCS, red ones are related to psychotic symptoms. (A) Pre-existing and persistent OCS. (B) Intermittent OCS during ARMS or later in the clinical course. (C) OCS-onset during ARMS and persistent course, strongly associated to the psychotic symptoms (schizo-obsessive concept). (D) Fluctuating course of OCS. (E) Second-onset OCS during antipsychotic treatmentApart from OCS during the ARMS a growing body of evidence investigated the co-occurrence of OCS during manifest schizophrenia. A significant subgroup within these patients reports OCS development after treatment-start with second generation antipsychotic agents (SGA). The order of the three events “onset of psychosis,” “start with SGA treatment” and subsequent “de novo development of OCS” hints toward the involvement of pharmacodynamic mechanisms (
  • Approaching the co-occurrence from the OCD spectrum, the concept of “schizotypic OCD” has been described (Poyurovsky and Koran, 2005; Poyurovsky et al., 2008). This concept assumes that primary OCD-patients present beliefs, which can be classified on a spectrum between obsessions and delusions emphasizing the similarities as being irrational thoughts, the first with insight and the latter lacking insight. In line with this concept, the category of “obsessions without insight” was integrated into the fourth edition of the Diagnostic and Statistical Manual (DSM IV). OCD-patients without insight might therefore represent a subgroup with genetic, phenotypic and therapeutic vicinity to the schizophrenia-like spectrum
  • MA Psychiatry. 2013 Nov;70(11):1190-9. doi: 10.1001/jamapsychiatry.2013.1932.Cognitive-behavioral therapy vsrisperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: a randomized clinical trial.Simpson HB, Foa EB, Liebowitz MR, Huppert JD, Cahill S, Maher MJ, McLean CP, Bender J Jr, Marcus SM, Williams MT, Weaver J, Vermes D, Van Meter PE, Rodriguez CI, Powers M, Pinto A, Imms P, Hahn CG, Campeas R.Author information Department of Psychiatry, Columbia University, New York, New York2New York State Psychiatric Institute, New York, New York.AbstractIMPORTANCE: Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).OBJECTIVE: To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.INTERVENTIONS: While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.MAIN OUTCOME AND MEASURE: The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.RESULTS: Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vsrisperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.CONCLUSIONS AND RELEVANCE: Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.
  • J Clin Psychiatry. 2006 Jan;67(1):15-22.High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial.Ninan PT, Koran LM, Kiev A, Davidson JR, Rasmussen SA, Zajecka JM, Robinson DG, Crits-Christoph P, Mandel FS, Austin C.Author information Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1841 Clifton Road, Atlanta, GA 30329, USA. pninan@emory.eduAbstractOBJECTIVE: To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment.METHOD: Sixty-six nonresponders to 16 weeks of sertraline treatment who met DSM-III-R criteria for current OCD were randomly assigned, in a double-blind continuation phase of a multicenter trial, either to continue on 200 mg/day of sertraline or to increase their dose to between 250 and 400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were collected from July 26, 1994, to October 26, 1995.RESULTS: The high-dose (250-400 mg/day, mean final dose = 357, SD = 60, N = 30) group showed significantly greater symptom improvement than the 200-mg/day group (N = 36) as measured by the YBOCS (p = .033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011). Responder rates (decrease in YBOCS score of > or = 25% and a CGI-I rating < or = 3) were not significantly different for the 200-mg/day versus the high-dose sertraline group, either on completer analysis, 34% versus 52%, or on endpoint analysis, 33% versus 40%. Both treatments showed similar adverse event rates.CONCLUSION: Greater symptom improvement was seen in the high-dose sertraline group compared to the 200-mg/day dose group during continuation treatment. Both dosages yielded similar safety profiles. Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment
  • Psychother Psychosom. 2012;81(6):366-74. doi: 10.1159/000339369. Epub 2012 Sep 6.Cognitive therapy versus fluvoxamine as a second-step treatment in obsessive-compulsive disorder nonresponsive to first-step behavior therapy.van Balkom AJ, Emmelkamp PM, Eikelenboom M, Hoogendoorn AW, Smit JH, van Oppen P.Author information Department of Psychiatry and EMGO Institute, VU University Medical Center, Academic Outpatient Clinic for Anxiety Disorders, GGZinGeest, Amsterdam, The Netherlands. t.vanbalkom@ggzingeest.nlAbstractBACKGROUND: To compare the effectiveness of second-step treatment with cognitive therapy (CT) versus fluvoxamine in patients with obsessive-compulsive disorder (OCD) who are nonresponsive to exposure in vivo with response prevention (ERP).METHODS: A 12-week randomized controlled trial at an outpatient clinic in the Netherlands comparing CT with fluvoxamine in OCD. Of 118 subjects with OCD treated with 12 weeks of ERP, 48 appeared to be nonresponders (Y-BOCS improvement score of less than one third). These nonresponders were randomized to CT (n = 22) or fluvoxamine (n = 26). The main outcome measure was the Y-BOCS severity scale. Statistical analyses were conducted in the intention-to-treat sample (n = 45) on an 'as randomized basis' and in the per-protocol sample (n = 30). Due to selective dropout in the fluvoxamine group, two additional sensitivity analyses were performed.RESULTS: Complete data could be obtained from 45 subjects (94%) after 12 weeks. Fifty percent of the patients refused fluvoxamine after randomization compared to 13% who refused CT [χ(2)(1) = 7.10; p = 0.01]. CT as a second-step treatment did not appear to be effective in this sample of nonresponders. Fluvoxamine was significantly superior to CT in the intention-to-treat sample, in the per-protocol sample and in the two separately defined samples in which the sensitivity analyses were performed.CONCLUSIONS: OCD patients who are nonresponsive to ERP may benefit more from a switch to treatment with an antidepressant instead of switching to CT. In clinical practice, it may be important to motivate this subgroup of patients to undergo psychopharmacological treatment, as this may improve their outcome considerably.
  • J Clin Psychiatry. 2004 Oct;65(10):1365-71.Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors.Maina G, Albert U, Salvi V, Bogetto F.Author information Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin, Torino, Italy. giuseppemaina@hotmail.comAbstractBACKGROUND: The effect of extended anti-depressant treatment on weight has been poorly investigated. Also unknown is whether different compounds have differential effects. The aim of the present study was to assess changes in weight in obsessive-compulsive disorder (OCD) patients treated for 2.5 years with clomipramine or selective serotonin reuptake inhibitors.METHOD: 138 DSM-IV OCD patients who responded to 6-month acute treatment at the Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin, Italy, were followed-up for 2 years while receiving open-label clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline. Patients were consecutively recruited and followed from May 1998 to March 2003. The mean percentage change in weight was compared for each group, as was the proportion of patients who had a > or = 7% weight increase from baseline.RESULTS: At the end of the 2.5-year study period, patients had gained a mean of 2.5% of their body weight with respect to baseline (1.58 kg); 14.5% of the total sample experienced a significant (> or = 7%) weight increase. Within each but the fluoxetine treatment group, paired t tests showed a significant increase in weight from baseline to final visit. Analysis of variance showed a significant difference between treatment groups (p = .009), with clomipramine being associated with the highest weight increase and fluoxetine and sertraline with the lowest. A higher proportion of clomipramine-treated patients (34.8%) gained > or = 7% in weight as compared with sertraline and fluoxetine, which accounted for the lowest percentage of patients with a significant weight gain (4.5% and 8.7%, respectively), although this difference was not statistically significant.CONCLUSION: Risk of weight gain during extended serotonin reuptake inhibitor treatment for OCD differs depending on which compound is used. The differences among antiobsessive drugs may affect compliance with medication and health risks.
  • 19.J Psychiatr Res. 2010 Mar;44(4):193-200. doi: 10.1016/j.jpsychires.2009.08.007. Epub 2009 Sep 15.Predictors of treatment response to fluvoxamine in obsessive-compulsive disorder: an fMRI study.Sanematsu H, Nakao T, Yoshiura T, Nabeyama M, Togao O, Tomita M, Masuda Y, Nakatani E, Nakagawa A, Kanba S.Author information Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.AbstractRecent neuroimaging studies suggest that the pathophysiology of obsessive-compulsive disorder (OCD) may involve more widely distributed large-scale brain systems, including the parietal, occipital, and cerebellar areas, rather than the conventional orbitofronto-striatal model. We hypothesized that not only orbitofrontal cortex and caudate nucleus activities but also posterior brain regions might be associated with subsequent treatment response to serotonin reuptake inhibitors in OCD. The participants were 17 patients with OCD. Each patient was required to undergo fluvoxamine pharmacotherapy for 12 weeks. Before treatment, fMRI images of the subjects were obtained in the context of a symptom-provocation paradigm. The percentage changes in total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, from pre- to post-treatment, served as the index of treatment response. Statistical Parametric Mapping was used to identify brain loci where pre-treatment brain activation significantly correlated with the subsequent treatment response. Fifteen of 17 patients completed the 12-week treatment. During the symptom provocation task, patients showed brain activation in the left superior temporal gyrus (STG), left precuneus, left frontal cortices, right cerebellum, and right frontal cortices. We found that pre-treatment activation in the right cerebellum (Z-score=5.10, x,y,z=22,-84,-18) and the left STG (Z-score=4.95, x,y,z=-62,-22,0) was positively correlated with the improvement in the Y-BOCS score. Our results suggest that pre-treatment activation in the right cerebellum and in the left STG predict subsequent reduction in OCD symptom severity. There is every possibility that fMRI can be used as a tool to predict treatment response.
  • The glutamate modulator riluzole acts (i) by inhibiting axonal voltage-gated sodium channels (Na+) – a mechanism shared with the antiepileptic agent lamotrigine – thereby limiting glutamate release; and (ii) by enhancing glial uptake of extrasynaptic glutamate. The antioxidant N-acetylcysteine (NAC) also modulates extrasynaptic glutamate; it is converted into cystine and drives the extrusion of glutamate from astrocytes via the cystine-glutamate antiporter. The NMDA blockers memantine and ketamine block the pore of the NMDA receptor, preventing cation influx. Glycine, D-serine, and D-cycloserine (D-CS), in contrast, bind to the NMDA receptor coagonist site and potentiate activation of the receptor. Sarcosine (not shown) inhibits the glycine receptor Gly-T, increasing the endogenous levels of glycine
  • Stereotactic placement of bilateral lesions in the anterior cingulate cortex: 28% response rate, with an additional 17% showing a partial response. A deep brain stimulation technique consists of implanting a device to electrically stimulate the subthalamic nucleus. There was significantly more improvement during the active stimulation periods. However, serious adverse events were substantial and included intracerebralhemorrhage and infection.In February 2009, the FDA approved the use of Reclaim Deep Brain Stimulation Therapy for individuals with chronic, severe OCD. This device is an implanted medical device that is designed to target a region called the ventral capsule/ventral striatum, which is in the anterior limb of the internal capsule of the brain

Transcript

  • 1. OCD : A Hidden Epidemic
  • 2. 30 years ago…..  Being diagnosed with obsessive-compulsive disorder (OCD) was about the closest thing the psychiatric world had to being given a life sentence…..  In addition to being seen as extremely rare, ….prognosis for those with a diagnosis of OCD was very poor….,  …..with no effective truly pharmacological or psychological treatments
  • 3. OCD  OCD is characterized by intrusive, troubling thoughts (obsessions), and repetitive, ritualistic behaviors (compulsions) which are time consuming, significantly impair functioning and/or cause distress  When an obsession occurs, it almost always corresponds with a massive increase in anxiety and distress. Subsequent compulsions serve to reduce this associated anxiety/distress. Lack CW, World J Psychiatry. 2012 Dec 22;2(6):86-90
  • 4. Prevalence of OCD  The lifetime prevalence rate of OCD is estimated at( USA)  2.3% in adults and  around 1%-2.3% in children and adolescents under 18.  Sub-clinical” cases of OCD (around 5% of the population)  Few epidemiological differences across different countries and even between European and Asian populations 1  Notably, 30-50% of patients develop OCD starting in childhood 2 1. Lack CW , World J Psychiatry. 2012 Dec 22;2(6):86- 2. Brian P. Brennan et al, Biol Psychiatry. 2013 Jan 1;73
  • 5. OCD in children and adolescents  Early-onset obsessive- compulsive disorder (OCD) is one of the more common mental illnesses of children and adolescents, with prevalence of 1% to 3%.  Its manifestations often lead to severe impairment and to conflict in the family Walitza S et al, Dtsch Arztebl Int. 2011 Mar;108(11
  • 6. OCD pathophysiology
  • 7. The CSTC circuitry implicated in OCD Pittenger C et al, Pharmacol Ther. 2011 Dec;132(3):314
  • 8.  Wu et al. [16] summarized the prior literature on the pivotal role of glutamate in corticostriatal- thalamocortical (CSTC) models of OCD.  One of the leading OCD models is based on the balance between direct and indirect pathways within CSTC circuits.  According to this theory, reciprocal interaction between direct (ultimately leads to thalamic stimulation of the cortex) and indirect (ultimately leads to thalamic inhibition of the cortex) pathways normally resulted in a dynamic balance with no one pathway predominating.  Hyperactivity of the direct pathway or hypoactivity of the indirect pathway would disinhibit CSTC circuits and promote consequent release of hardwired behaviors (compulsions) and cognitions (obsessions) that were normally held in check
  • 9. Pathophysiology of OCD  As yet Unknown  Abnormalities in the orbital (OFC), ventromedial (vmPFC-subgenual cingulate and medial OFC), and dorsal anterior cingulate (dACC) cortical-basal ganglia circuits  OCD-linked patterns of activity in these PFC regions are accentuated during provocation of symptoms  They can predict treatment response  They tend to normalize following successful treatment Haber SN et al, Neuropsychopharmacology. 2013 Ja
  • 10. Neurotransmitter alterations in OCD??  Linkage of OCD risk with polymorphisms in the serotonin transporter  Increased serotonin in peripheral blood has been reported in OCD  Abnormalities in dopamine neurotransmission in OCD: A reduction in the dopamine D2 receptor  Abnormalities in glutamate neurotransmission and homeostasis, especially in the CSTC circuitry Pittenger C et al, Pharmacol Ther. 2011 Dec;132(3):314
  • 11. NeuroCircuitry Abnormalities in OCD  Changes in vmPFC/OFC/dACC activity  Overlap in the circuits  Dysfunction of the vmPFC/OFC/dACC network  PFC regions associated with OCD pathology Haber SN et al, Neuropsychopharmacology. 2013 J
  • 12. Genetic factors and OCD  Twin studies reveal a higher concordance of OCD in  monozygotic twins (80–87%) than in dizygotic twins (47–50%)  Genetic factors appear to have a substantial role in the etiology of early- onset OCD. Wu K et al, Pharmacol Biochem Behav. 2012 Feb;100(4):726-3
  • 13. Glutamate Related Genes implicated in OCD Several glutamate-related genes have been associated with OCD risk.  The glutamate transporter gene Slc1A1  The Sapap3 gene, is critical to the normal localization of ionotropic glutamate receptors  The Grin2B gene may be associated with OCD transmission  The Grik2 locus is involved in glutamate neurotransmission Pittenger C et al, Pharmacol Ther. 2011 Dec;132(
  • 14. Disrupted neurotransmission of glutamate in OCD  Disrupted neurotransmission of glutamate within corticalstriatal- thalamocortical (CSTC) circuitry  Plays a role in OCD pathogenesis.  Associations between variants for SLC1A1 Wu K et al, Pharmacol Biochem Behav. 2012 Feb;1
  • 15. Proinflammatory cytokines in OCD  Significant reduction in IL-1β levels  Lower plasma IL-6 levels.  Elevated TNF-α levels in individuals with comorbid depression. Gray SM et al, Curr Psychiatry Rep. 2012 Jun;14(3)
  • 16. Diagnosis of OCD
  • 17. ICD-10 criteria for obsessive-compulsive disorder (age-independent)*  For a definite diagnosis, obsessional symptoms or compulsive acts, or both, must be present on most days for at least 2 successive weeks and be a source of distress or interference with activities.
  • 18. ICD-10 criteria for obsessive-compulsive disorder (age-independent)* The obsessional symptoms should have the following characteristics:  They are acknowledged as originating in the mind of the patient, and are not imposed by outside persons or influences.  At least one obsession or compulsion must be present which is unsuccessfully resisted.  Carrying out the obsessive thought or compulsive act is not in itself pleasurable.  The thoughts, images, or impulses must be unpleasantly repetitive
  • 19. ICD-10 criteria for obsessive-compulsive disorder (age-independent)*  The patient must suffer from obsessions and/or compulsions, i.e., thoughts and/or behavioral impulses.  At least one of these obsessions and/or compulsions must be resisted.  The patient does not perceive the manifestations of the disorder as being pleasurable.  The obsessions and/or compulsions occur repetitively; the patient is troubled by them and is markedly impaired by them.
  • 20. DSM V and OCD changes : Unnecessay but harmless?  The APA is considering changing the name of this category to Anxiety and Obsessive-Compulsive Spectrum Disorders.  Obsessive-Compulsive Disorder removed from the Anxiety Disorders category, and reclassified in its own category.  Reason : OCD has a neurological basis. …
  • 21. DSM V and OCD changes  The DSM-IV focus was not on the cause of the but rather on the presenting symptoms that define the conditions.  One of the primary defining characteristics of OCD is anxiety.  The one common factor - they are highly anxious about their obsessive and compulsive symptoms.
  • 22. OCD and DSM-V: Taking the “anxiety” out of OCD  Psychiatrists and psychologists debate whether or not OCD should continue to be classified as an “anxiety disorder.”  In some ways, OCD overlaps with other anxiety-related conditions, such as  panic disorder  Phobias  social anxiety disorder  generalized anxiety disorder, and  post-traumatic stress disorder (PTSD).
  • 23. DSM V and OCD  The new Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)  Has a number of changes to obsessive-compulsive and related disorders, such as hoarding and body dysmorphic disorder.  A separate chapter for OCD and related disorders  They are no longer considered “anxiety disorders.  Disorders in this chapter include  obsessive-compulsive disorder,  body dysmorphic disorder and  trichotillomania (hair-pulling disorder), as well as two new disorders:  hoarding disorder and excoriation (skin-picking) disorder.
  • 24. DSM-5  Obsessive-compulsive and related disorders can include  body-focused repetitive behavior disorder and  obsessional jealousy, or unspecified obsessive- compulsive and related disorder.  Body-focused repetitive behavior disorder, is characterized by recurrent behaviors other than hair pulling and skin picking (e.g., nail biting, lip biting, cheek chewing) and repeated attempts to decrease or stop the behaviors.  Obsessional jealousy is characterized by nondelusional preoccupation with a partner’s perceived infidelity.
  • 25. Diagnosis with the Y-BOCS  Define the range and severity of OCD symptoms  The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a good tool  Complete Mental Status Examination  Look for comorbid symptoms and
  • 26. Imaging studies  Functional MRI and PET scanning demosntrate  increase in blood flow and metabolic activity in the orbitofrontal cortex, limbic structures, caudate, and thalamus  with a trend toward right-sided predominance.  Areas of overactivity have been shown to normalize following successful treatment with either SSRIs or CBT.  These imaging modalities, are of value for research  They are not indicated for normal workups.
  • 27. OCD Presenting Features
  • 28. Common obsessions  Contamination fears  Worries about harm to self or others  The need for symmetry, exactness and order,  Religious/moralistic concerns  Forbidden thoughts (e.g., sexual or aggressive), or  A need to seek reassurance or confess Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 29. Common obsessions  Safety  Doubting one's memory or perception  Scrupulosity (need to do the right thing, fear of committing a transgression, often religious)  Need for order or symmetry  Unwanted, intrusive sexual/aggressive thought
  • 30. Common compulsions  Cleaning/washing  Checking  Counting  Repeating  Straightening  Routinized behaviors  Confessing  Praying  Seeking reassurance  Touching  Tapping or rubbing, and  Avoidance Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 31. Common compulsions  Checking (eg, locks, stove, iron, safety of children)  Counting/repeating actions a certain number of times or until it "feels right"  Arranging objects  Touching/tapping objects  Hoarding  Confessing/seeking reassurance  List making
  • 32. Gender differences  More common in males in pediatric patients.  There are some differences in comorbidity as well.  Among men, hoarding symptoms are most often associated with GAD and tic disorders.  In women social anxiety, PTSD, body dysmorphic disorder, nail biting, and skin picking are more often observed Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 33. Cultural influences on symptom expression  Bali: Heavy emphasis on somatic symptoms and need to know about members of their social network  Jews: Emphasis on cleanliness and order  Muslims : Religious obsessions in Muslim communities  South America : Aggressive aggressions  USA : Dirt and contamination worries Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 34. OCD in children
  • 35. OCD in children  Presentation of OCD symptoms is similar in children and adults.  Younger children will not be able to recognize that their obsessions and compulsions are both unnecessary  In young children, compulsions often occur without the patient being able to report their obsessions  Adolescents are often able to report multiple obsessions and compulsions. Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 36. OCD in children  Children and adolescents are also more likely to include family members in their rituals  Can be highly demanding of adherence to rituals and rules, leading to disruptive and oppositional behavior and even episodes of rage.  Youth with OCD are generally more impaired than adults with the same type of symptoms Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 37. OCD and comorbid disorders
  • 38. Comorbid disorders with OCD  Up to 75% of persons with OCD present with comorbid disorders.  In pediatric cases : ADHD, disruptive behavior disorders, major depression, and other anxiety disorders.  In adults: Social anxiety, major depression, and alcohol abuse. Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 39. Comorbid disorders with OCD  Primary symmetry/ordering symptoms are often seen with  comorbid tics  bipolar disorder  obsessive-compulsive personality disorder  panic disorder, and agoraphobia  Those with contamination/cleaning symptoms are more likely to be diagnosed with an eating disorder.  Those with hoarding cluster symptoms, are likely to be diagnosed with personality disorders, particularly Cluster C disorders Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 40. OCD and schizophrenia  The mean OCD prevalence is 13.6%  The prevalence rate of OCS, defined as any obsession or compulsion is 30.7%  The prevalence of OCS and OCD in schizophrenia is substantial, specifically in more chronic patient populations  It is influenced by the method of assessment Swets M, Schizophr Res. 2013 Dec 19. pii: S0920-9964(13)00
  • 41. Prevalence estimations of OCS and OCD within different samples of patients Schirmbeck F, Front Pharmacol. 2013 Aug 9;4:99.
  • 42. Onset of OCS  First onset of OCS has been described at different stages during the course of psychotic illness:  Before psychosis as independent, co-existing symptoms or diagnosed OCD.  Prior to psychotic manifestation as part of the at risk mental state (ARMS).  Simultaneously with the first manifestation of psychosis.  After the first psychotic episode during the course of chronic schizophrenia.  As de novo OCS after initiation of antipsychotic treatment. Schirmbeck F, Front Pharmacol. 2013 Aug 9;4:99.
  • 43. OCS might manifest at different time points during the course of schizophrenia illness (A) Pre-existing and persistent OCS. (B) Intermittent OCS during ARMS or later in the clinical course. (C) OCS-onset during ARMS and persistent course, strongly associated to the psychotic symptoms (schizo-obsessive concept). (D) Fluctuating course of OCS. (E) Second-onset OCS during antipsychotic treatment Schirmbeck F, Front Pharmacol. 2013 Aug
  • 44. Identification of obsessive-compulsive symptoms in schizophrenia. Insight-criterion Patients suffering from OCD typically fulfill three symptom characteristics: they attribute the obsessions, impulsive symptoms and compulsions to their own thinking, declare with insight their unreasonableness and show some degree of resistance against them. In particular the first two properties allow a differentiation from hallucinations and delusions. Ruminations or stereotypic ego-dystonic cognitions with direct relation to the contents to psychotic thinking should not be diagnosed as obsessions. OCS not solely related to the psychotic content Cleaning or checking behavior should be diagnosed as compulsions only if it is accompanied by typical obsessions and not, if the patient currently suffers from delusions of contamination, intoxication or infection. Re-evaluation of OCS after remission of psychotic symptoms If first manifestation of OCS occurs simultaneously with the first psychotic exacerbation, the final decision on a valid comorbid condition should be postponed until the remission of psychotic symptoms. Schirmbeck F, Front Pharmacol. 2013 Aug 9;4
  • 45. Identification of obsessive-compulsive symptoms in schizophrenia. Differentiation from catatonic symptoms Repetitive behavior or stereotypic actions should carefully be discriminated from catatonic symptoms most importantly in patients with so- called “manieristic catatonia.” Obsessions presented as pseudohallucinations A subgroups of OCS patients, who experience their obsessions as extremely aversive and burdening may try to distance themselves by using expressions such as “voices” or “foreign thought content”, but in most cases these phenomena can be characterized as pseudohallucinations. SGA-induced OCS Patients without a previous history of OCS might develop these phenomena during antipsychotic treatment. This constellation hints toward the unfavorable effect of second-onset OCS induced by SGAs. Schirmbeck F, Front Pharmacol. 2013 Aug 9;4:99.
  • 46. Factors for occurrence of OCS  The additional occurrence of OCS is associated with  high subjective burden of disease  additional neurocognitive impairment  poorer social and vocational functioning  greater service utilization  high levels of anxiety and depression. Schirmbeck F,Front Pharmacol. 2013 Aug 9;4
  • 47. Hypothesis for OCD + Schizophrenia  Patients with schizophrenia develop OCS as an attempt to reduce psychotic symptoms ??  The presence of OCS was proposed to have protective effects??  Negative correlations between specific OCS and the severity of psychotic disorganization in thinking and behavior, may be due to compensating mechanisms?? Schirmbeck F,Front Pharmacol. 2013 Aug 9;4
  • 48. Schizotypic OCD  Primary OCD-patients present beliefs, which can be classified on a spectrum between obsessions and delusions emphasizing the similarities as being irrational thoughts, the first with insight and the latter lacking insight. Schirmbeck F,Front Pharmacol. 2013 Aug
  • 49. Neurobiological mechanisms in OCD and schzophrenia  Pronounced cognitive deficits reflect an underlying neurobiological risk factor for schizophrenia patients to develop OCS and mirror at least partially overlapping neurobiological mechanisms with OCD  Serotonergic dysfunctions, alterations in dopaminergic activity and in glutamatergic neurotransmission, have also been related to OCD Schirmbeck F,Front Pharmacol. 2013 Aug
  • 50. Impact of OCD on QoL  Almost all adults and children with OCD report that their obsessions cause them significant distress and anxiety  A pervasive decrease in QOL  Youth show problematic peer relations, academic difficulties, sleep problems, and participate in fewer recreational activities Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 51. OCD and bipolar disorder  Obsessive compulsive features occurring in mania have been well documented.  There are very few case reports and studies in India  This is a complex comorbidity to treat as OCD requires high doses of SSRIs which precipitates mania.  A sound knowledge of etiology and the pathology operating gives an insight into the comorbidity Annigeri B, Indian J Psychol Med. 2011 Jan;33(1):83-5
  • 52. Treatment of OCD and bipolar disorder  Treatment guidelines may differ as compared with that of pure cases.  BPD also responds poorly to mood stabilizing antipsychotics like olanzapine in the presence of OCD.  BPD receives preference with regards to treatment Annigeri B, Indian J Psychol Med. 2011 Jan;33(1):83-5
  • 53. Treatment options for OCD
  • 54. Cognitive-behavioral therapy (CBT)  The psychological treatment of choice for OCD  Effective in both adults and children  Is backed by numerous clinical trials  Particularly exposure with response prevention (EX/RP) Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 55. CBT  It is superior to medications alone, with effect sizes ranging from 1.16-1.72  There is a lower relapse rate than in medications (12% vs 24%-89%)  Up to 25% of patients will drop out prior to completion of treatment due to the nature of treatment.  The course of therapy generally lasts between 12-16 sessions Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 56. Differing responses to CBT  Those with hoarding cluster symptoms respond less well to CBT  Accommodation by family members in pediatric clients is predictive of poorer treatment response as well.  Intriguingly, group therapy that uses CBT and EX/RP has been shown to be equally as effective as individual therapy  For persons with mild OCD, computer-assisted self-treatment has been shown to be very effective Lack CW , World J Psychiatry. 2012 Dec 22;2
  • 57. Pharmacological treatment  Treatment is targeted primarily at monoaminergic neurotransmission, particularly at the serotonin and dopamine systems.  The SSRIs are the mainstay of pharmacotherapy  The SSRIs are of benefit in 50–60% of patients Pittenger C et al, Pharmacol Ther. 2011 Dec;132
  • 58. Drug therapy First-line pharmacologic treatments consist of  5-HT reuptake inhibitors, such as the SSRIs (fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram),  Clomipramine  TCA with 5-HT and NE reuptake inhibition.  Venlafaxine (SNRI).
  • 59. SSRIs  SRIs can be successfully supplemented with adjunctive antipsychotics  Only a third of patients will show improvements and there are serious health concerns with their long-term usage. Lack CW, World J Psychiatry. 2012 Dec 22;2(6):86-90
  • 60. Indian experience with SSRIs in OCD  The study examined the 5-year course prospectively in 115 OCD outpatients who were mostly treated with serotonin reuptake inhibitors (SRIs).  The outcome of OCD seems to be better than generally assumed, at least in moderately ill outpatients.  Regular treatment over extended period may enhance likelihood of remission.  Full remission should be the goal of treatment since it is associated with lesser propensity for relapse.  Most patients remit in the first 2 years of treatment; therefore, early detection and intervention may improve the outcome. Cherian AV et al, J Affect Disord. 2014 Jan;152- 154:387-94
  • 61. Clinical Pearls  Adding ERP to SRIs was superior to both risperidone and pill placebo.  Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered ERP before antipsychotics given its superior efficacy and less negative adverse effect profile. Simpson HB JAMA Psychiatry. 2013 Nov;70(11):1190
  • 62. Clinical Pearls  Augmenting SRIs with exposure and ritual prevention versus stress management training leads to better outcome after acute treatment and 24 weeks later  The response in combination group was significantly higher starting from 9th week, continuing up to 13th week. Mean symptom reduction and mean percentage reduction of symptoms were also higher in the case of combination group. Foa EB, J Clin Psychiatry. 2013 May;74(5):464-9 Giasuddin NA, Pak J Pharm Sci. 2013 Jan;26(1):95-8
  • 63. Clinical Pearls  About one-third of SRI-resistant OCD patients benefited from an augmentation strategy with antipsychotics.  Based on the favourable risk:benefit ratio, risperidone can be considered as the agent of first choice and should be preferred to quetiapine and olanzapine. Dold M, Int J Neuropsychopharmacol. 2013 Apr;16(3):5
  • 64. Sertraline for non responders of OCD  Greater symptom improvement was seen in the high-dose sertraline group compared to the 200- mg/day dose group during continuation treatment.  Both dosages have similar safety profiles.  Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment Ninan PT, J Clin Psychiatry. 2006 Jan;67(1):15
  • 65. Fluvoxamine Vs Clomipramine in OCD 67
  • 66. Fluvoxamine Vs Clomipramine in OCD Presentation Title Date 68  Study objective: To directly compare the efficacy and safety of fluvoxamine and clomipramine in patients with OCD  Study Design: Double-blind, randomised, multicentre study  Patient population: 227 patients with a primary diagnosis of OCD  Evaluation parameters:  Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)  National Institute of Mental Health Obsessive-Compulsive (NIMH-OC) scale  Global Improvement item of the Clinical Global Impression (CGI) scale Mundo E. Hum Psychopharmacol. 2001 Aug;16(6):461-468.
  • 67. Fluvoxamine Vs Clomipramine in OCD 69 Fluvoxamine and clomipramine were equally effective, both resulting in clinically significant improvement Mundo E. Hum Psychopharmacol. 2001 Aug;16(6):461-468.
  • 68. Fluvoxamine Vs Clomipramine in OCD 70 Mundo E. Hum Psychopharmacol. 2001 Aug;16(6):461-468. Fluvoxamine and clomipramine were equally effective on secondary endpoints variable
  • 69. Fluvoxamine Vs Clomipramine in OCD 71 Mundo E. Hum Psychopharmacol. 2001 Aug;16(6):461-468. Fluvoxamine was better tolerated than clomipramine The overall incidence of premature withdrawal due to adverse events was twice as high as with clomipramine than with fluvoxamine (16% Vs 8%)
  • 70. Cognitive therapy versus fluvoxamine as a second- step treatment in obsessive-compulsive disorder nonresponsive to first-step behavior therapy  OCD patients who are nonresponsive to ERP (exposure in vivo with response prevention) may benefit more from a switch to treatment with an antidepressant instead of switching to CT  In clinical practice, it may be important to motivate this subgroup of patients to undergo psychopharmacological treatment, as this may improve their outcome considerably van Balkom AJ, Psychother Psychosom. 2012;81(6):366-
  • 71. Weight gain with SSRIs  Clomipramine,, citalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline  At the end of the 2.5-years patients had gained a mean of 2.5% of their body weight with respect to baseline (1.58 kg)  Higher proportion of clomipramine-treated patients (34.8%) gained > or = 7% in weight as compared with sertraline and fluoxetine  Sertraline and fluoxetine had the lowest percentage of patients with a significant weight gain (4.5% and 8.7%, respectively),Maina G, J Clin Psychiatry. 2004 Oct;65(10):1365-71.
  • 72. Clinical Pearls : Treatment predictors for fluvoxamine  Pre-treatment activation in the  right cerebellum (Z-score=5.10, x,y,z=22,-84,- 18) and  the left STG (Z-score=4.95, x,y,z=-62,-22,0) was positively correlated with the improvement in the Y-BOCS score.  Pre-treatment activation in the right cerebellum and in the left STG predict subsequent reduction in OCD symptom severity.  There is every possibility that fMRI can be used as a tool to predict treatment response. Sanematsu H et al, J Psychiatr Res. 2010 Mar;44(4):193-20
  • 73. Major sites of action of glutamate- modulating drugs Pittenger C et al, Pharmacol Ther. 2011 Dec;132
  • 74. Differing responses  The presence of tics appears to decrease selective SRI effects in children, but it is unclear if it has the same effect in adults.  Another known difference is that patients who have OCD with comorbid tics respond better to neuroleptic drugs than those who have OCD without tics Lack CW, World J Psychiatry. 2012 Dec 22;2(6):86-90
  • 75. Clinical Pearls  Unlike in the case of major depression, complete or near-complete remission of OCD symptoms is rare with only serotonergic antidepressant treatment.  More typically, perhaps half of patients may experience symptom reductions of 30-50%, with many other patients failing to achieve even this degree of relief.  Doses above those needed for treatment of depression may be more effective for some patients.  A therapeutic dose for 6-10 weeks may be required to observe a clinical response.  Response tends to be slow and continues for at least 12 weeks
  • 76. Clinical Pearls  For reasons that remain unclear, higher doses than those used for depression are often required for OCD  In disease refractory to these agents, pharmacological augmentation with neuroleptic drugs, which antagonize the D2 dopamine receptor, can be efficacious Pittenger C et al, Pharmacol Ther. 2011 Dec;132
  • 77. Clinical Pearls Role of life events in obsessive compulsive disorder.  Life events are significantly more frequent in OCD patients  The severity of OC symptoms is directly proportional to the number of stressful life events experienced in the last six months prior to onset. Sarkhel S et al, Isr J Psychiatry Relat Sci. 2011;48(3):182-5.
  • 78. Alternative agents  Use of specific glutamatergic agents (eg, memantine, N -acetylcysteine, riluzole, topiramate, glycine) Sarkhel S et al, Isr J Psychiatry Relat Sci. 2011;48(3):182-5.
  • 79. ERP treatment  ERP is now usually administered as part of a broader program of CBT specifically designed for OCD.  After making the patient aware of his or her irrational thoughts, the therapist works to have the patient counter them with more rational thoughts and do cost/benefit analyses regarding performing his or her rituals.
  • 80. Treatment resistance strategies  Strategies should always include an assessment of  complicating diagnoses  medication compliance  drug dose, and  duration of therapy.  Comorbid diagnosis such as depression or panic disorder, can interfere with clinical recovery, and identification may guide the choice of interventions. William M Greenberg, Obsessive-Compulsive Disorder Treatment & Management.www.medscape.com
  • 81. Treatment resistance strategies  Interventions for patients with treatment resistance include  Change or increase in medication  More intensive CBT  Other interventions, which have not received an FDA indication for OCD include the following:  Addition of an NE reuptake inhibitor, such as desipramine, to an SSRI, or a trial of venlafaxine  Addition of a typical or atypical antipsychotic, especially in patients with a history of tics William M Greenberg, Obsessive-Compulsive Disorder Treatment & Management.www.medscape.com
  • 82. Treatment resistance strategies  Interventions for patients with treatment resistance include  Augmentation with buspirone  Addition of inositol  Sole or augmented use of selected glutamatergic agents  Deep brain stimulation or cingulotomy neurosurgery or severe and intractable cases  Some clinicians feel that individuals with comorbid Tourette disorder or with hoarding as their principal OCD symptom may be more likely to be treatment resistant, although there is significant variation in treatment response, regardless of the particular presenting symptomatology. William M Greenberg, Obsessive-Compulsive Disorder Treatment & Management.www.medscape.com
  • 83. Low-frequency rTMS over the SMA for treatment-refractory patients of OCD  Novel treatment strategies like repetitive transcranial magnetic stimulation (rTMS) have been proposed for OCD refractory to standard treatments  Low-frequency rTMS over the SMA appears a promising treatment strategy as an add-on treatment in treatment-refractory patients of OCD. Kumar N et al,Indian J Psychiatry. 2011 Oct;5
  • 84. Neurosurgical treatment of OCD  Neurosurgical treatment of OCD is reserved for patients with severe and refractory symptoms.  The most common small series use a specific small lesion (eg, cingulotomy) or deep brain stimulation.  Current clinical trials are also exploring the application of transcranial magnetic stimulation (TMS), a noninvasive treatment, for OCD. William M Greenberg, Obsessive-Compulsive Disorder Treatment & Management.www.medscape.com
  • 85. Neurosurgical treatment of OCD  Stereotactic placement of bilateral lesions in the anterior cingulate cortex: 28% response rate, with an additional 17% showing a partial response.  A deep brain stimulation technique consists of implanting a device to electrically stimulate the subthalamic nucleus William M Greenberg, Obsessive-Compulsive Disorder Treatment & Management.www.medscape.com
  • 86. FUTURE DIRECTIONS FOR RESEARCH  Treatment dissemination, particularly for CBT and EX/RP, remains an issue  Steps can and should be undertaken to improve dissemination of CBT  Dissemination of both the safety and effectiveness of exposure-based therapies to both the general public and mental health clinicians  More research on how certain comorbidity patterns impact treatment
  • 87. Study further … New Promising approaches  Targeting the extinction learning core to EX/RP with d-cycloserine , a partial agonist at the NMDA receptor in the amygdala  Novel combinations of pre-existing treatments
  • 88. End Note  There is truly not a better time in history to have OCD than the present,….  …. given the multiple effective pharmacological agents, psychological therapy, and ….an ever- increasing understanding of the disorder itself.  This is not, however, the time to sit back and pat our collective backs in triumph.