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OCD and Psychiatric Co-morbidities : 

OCD and Psychiatric Co-morbidities Deepak Joshi Med/Psych PGY-4



Learning Objectives : 

Learning Objectives Neuro-circuitry of OCD in the context of an anxiety disorder. Discuss similarities between OCD and the OCD spectrum disorders. Demonstrate awareness of the high co-morbidity of psychiatric disorders in OCD and OCD Spectrum disorders. Understand treatment responsiveness along the compulsive – Impulsive dimension, keeping OCD spectrum disorders in mind.

Outline : 

Outline Neuro circuits in Anxiety. Neuro circuits in OCD. OCD Spectrum disorders. Co-morbidities with OCD. Treatment options for OCD.

Prevalence : 

Prevalence 2% to 3% afflicted worldwide. [5]. The rates are consistent across most cultures. Males with an earlier onset - have a worse course than females. Symptoms are present an average of 10 years prior to clinical presentation. Patients with OCD often feel shame regarding their symptoms and put great effort into concealing them from family, friends, and health care providers.

Prevalence Contd. : 

Prevalence Contd. Sex: Equal in males and females. Childhood-onset OCD is more common in males and more likely to be linked genetically with ADHD and Tourette syndrome. Age: Symptoms usually begin in individuals aged 10-24 years.

Introduction : 

Introduction OCD is an anxiety disorder. For diagnosis, either obsessions and/or compulsions must be present. Although many different types of cognitive and behavioral symptoms are present in OCD, anxiety appears to underlie both obsessive thoughts and compulsive behaviors.

Anxiety disorders : 

Anxiety disorders Fear Worry

Anxiety : 

Anxiety Start from Amygdla. Fear – Ventro-Medial prefrontal cortex. Worry – Dorsolateral PFC.

Anxiety : 

Anxiety Fear: If episodic – Panic attacks or panic disorder. Social phobia etc. Generalized anxiety.

Anxiety : 

Anxiety Worry: like a thought. Can be random or evoke fear. Cortico Striatal Thalamo Cortical loop. (Worry loop). If afraid – Paranoia. If excessive – Obsession.

Worry vs Obsession : 

Worry vs Obsession Worry: Perceived, as triggered by internal or external event. Content – normal everyday experiences (family, finances etc) - Worry: is in the form of a thought. Obss: as thoughts, images or impulses. Worry does not appear to be resisted as strongly nor it is as intrusive, as obsessional thinking.

Associated Symptoms : 

Associated Symptoms Amygdla ? different structures in the brain stem. Hypothalamus – Cortisol. Locus Ceruleus – Tachycardia. Parabrachial Nuclei – Tachypnea. Periaqueductal gray – Fight, Flight or Flee.

Slide 16: 

Neuro circuits in Anxiety Neuro circuits in OCD. OCD Spectrum disorders. Co-morbidities with OCD. Treatment options for OCD.

DSM Classification : 

DSM Classification Obsession &/Compulsion. Recognized as excessive or unreasonable. Causes marked distress, time consuming (> 1hr/day) or interferes with functioning. Content is not due to Axis I disorder. Not due to substance abuse or Gen medical condition. Specify: Poor insight type (--10% of pts).

Major Symptom factor of OCD. : 

Major Symptom factor of OCD. Aggression / Harm obsession and checking compulsion. Contamination obsession and cleaning compulsion. Symmetry / order obsession and arranging or precision compulsion. Saving / Collecting obsession and hoarding/saving compulsion.

Neural correlates of OCD Symptom factors : 

Neural correlates of OCD Symptom factors Aggression / Harm Contamination Symmetry / Order Saving / Collection Increased activity of striatum Increased activity of Orbito frontal cortex & Anterior Cingulate Gyrus. Decreased activity of striatum Decreased activity of Cingulate gyrus. Ranch et al 1998; Saxena et al 2003.

Etiology of OCD. : 

Etiology of OCD. Is not known. Genetic: In some cohorts, OCD, ADHD, and Tourette syndrome/tic disorders co-vary in an autosomal dominant fashion with variable penetrance. Infectious: PANDAS - group A streptococcal infections, herpes simplex virus. These infections trigger a CNS immune response that produces neuropsychiatric symptoms.

Etiology contd. : 

Etiology contd. Stress: worsens OCD symptoms. Interpersonal relationships: OCD symptoms can interact negatively with interpersonal relationships, and families can become involved with the illness in a counterproductive way. Parenting style or upbringing does not appear to be a causative factor in OCD

Slide 25: 

Self Stimulation PleasureImpulse control disorder-Gambling-Sex-Shopping-Hair pulling-Fire setting StereotypesAutism-Rocking-Head banging-Echolalia Tourettes -Tics Reward deficient statesADHDAddiction disorders-Substance use-Sexual addictions Self Stimulation & Repetitive Behaviors

Slide 26: 

CompulsivityDrive: Discomfort ImpulsivityDrive: Pleasure/Pain Inability to delay Repetitive Behavior

Slide 27: 

Neuro circuits in Anxiety Neuro circuits in OCD. OCD Spectrum disorders. Psychiatric Co-morbidities with OCD. Treatment options for OCD.

Slide 28: 

OCD Neurologic Tourettes Sydenhams ch. Torticolis Autism Preoccupation with bodily sensation or appearance Impulsive disorders Sexual Compulsions Trichotillomania Pathological gambling Kleptomania Self injurious behaviors BDD Depersonalization Anorexia Nervosa Hypochondriasis OCD Spectrum disorders

OCD Spectrum : 

OCD Spectrum OCD BDD A.N. DEP HYPO. T.S. Trich Binge Eating Comp. Buy Klep PG Sexual Comp. BPD. Anti Social PD Compulsive Impulsive Risk Aversive Risk Seeking

Slide 30: 

Awareness of the high co-morbidity of these d/o with one another and with other psychiatric d/o, esp mood d/o. Trt responsiveness will also vary along the compulsivity-impulsivity dimension. Consideration of an OCD spectrum d/o in pt inadequately responsive to standard trt might lead to consideration of other, possibly more effective intervention (eg. Delusional d/o not responsive to antipsychotic might be in fact a delusional OCD spectrum d/o preferentially responsive to SRIs). Clinical Implications

Slide 31: 

Neuro circuits in Anxiety Neuro circuits in OCD. OCD Spectrum disorders. Psychiatric Co-morbidities with OCD. Treatment options for OCD.

Psychiatric co-morbidities : 

Psychiatric co-morbidities Personality disorders MDD Simple phobia Social phobia Eating disorders Bipolar disorder Alcohol abuse Comorbidities Estimated prevalence 63 % 28 to 31% 7 to 48% 11 to 16% 15% 8 to 13% 8% Panic disorder 6 to 12 %

Is OCD Primary : 

Is OCD Primary OCD-like obsessive thoughts or repetitive behaviors may be evident in a number of psychiatric disorders. Distinguishing OCD from masquerading or co-occurring conditions is important because interventions can differ.

OCD contd. : 

OCD contd. GAD - ruminative, anxious thoughts that mimic obsessions. Somatoform conditions : (hypochondriasis or body dysmorphic disorder) - intense preoccupation with illness or appearance. Repetitive or compulsive behaviors may be seen in impulse control or developmental disorders such as pathologic gambling, trichotillomania, and Asperger’s disorder.

How to differentiate : 

How to differentiate Consider the function of a patient’s symptoms. In OCD, obsessions - ego-dystonic ? great anxiety. OCD patients perform compulsive rituals to alleviate anxiety but do not gain pleasure from their actions. Trichitollomania’s — commonly experienced as pleasurable or gratifying. GAD’s ruminative thoughts — seen as ego-syntonic worries about real-life situations.


ASSESSING OCD, COMORBID CONDITIONS In specialty OCD clinics, the Structured Clinical Interview for DSM-IV (SCID-IV)15 or Anxiety Disorders Interview Schedule for the DSM-IV (ADIS-IV)10 are routinely given to assess the most common comorbid conditions. In clinical practice, however, these instruments can take up to several hours to perform, especially for patients who meet criteria for several disorders.


ASSESSING OCD, COMORBID CONDITIONS Anxiety Disorders Interview Schedule-IV (ADIS-IV) Mini-International Neuropsychiatric Interview (MINI) 15 to 30 min 2+ hrs Detailed assessment of anxiety disorders Brief screen for diagnosis Structured clinical interviews Time Use

OCD-specific measures : 

OCD-specific measures Yale-Brown Obsessive Compulsive Scale (YBOCS) Obsessive Compulsive Inventory-Revised (OCI-R) 5 to 10 min 30 min Severity and OCD symptom types Self-report severity of OCD symptoms Structured clinical interviews Time Use

OCD Severity : 

OCD Severity The Yale-Brown Obsessive Compulsive Scale (YBOCS) is widely used.12,13 It includes a checklist of common obsessions and compulsions plus 10 items measuring interference with daily living, distress, resistance, control, and time spent on symptoms. Each item is scored from 0 to 4, for a total score of 0 to 40.

OCD Severity : 

OCD Severity The YBOCS has good reliability and validity. Is available in both clinician-rated and self-rated versions. Can be given repeatedly to measure treatment progress. A Children’s Yale-Brown Obsessive-Compulsive Scale (CYBOCS) is useful for patients ages 6 to 17.16


TREATING UNCOMPLICATED OCD CBT: first line treatment for only OCD, w/o other concurrent diagnosis (expert consensus guidelines) 17. Exposure and response prevention (ERP) therapy which is the specialized CBT for reducing anxiety that triggers obsessive-compulsive symptoms — report reduced symptoms and often maintain those gains over time.18


TREATING UNCOMPLICATED OCD ERP for 2 hours / day, 3 to 5 times per week for about 3 weeks (Specialty clinics). Although studies find excellent outcomes with intensive OCD treatment,18 it is not always practical or indicated (as in patients with moderate symptoms). Less-intensive protocols, such as biweekly sessions, have also shown promise in studies.19

Behavioral therapy : 

Behavioral therapy 20% to 25% refuse to go through the therapy. The patient may not comply with the therapeutic directions, including homework. Pt may substitute ritualistic thoughts in place of overt behaviors to diminish the anxiety. (This will defeat the purpose of the behavioral interventions, although it might appear on the surface that the individual is improving). Finally, - limited availability of behavioral programs.

Other treatments : 

Other treatments Functional imaging studies suggest that OCD results from dysregulation in the so called “OCD circuit”—the orbitofrontal cortex, anterior cingulate, and caudate nucleus. In patients with OCD, metabolic activity in this region is increased at rest relative to controls, increases further with symptoms, and decreases after successful treatment.21

OCD : 

OCD The serotonin hypothesis—which emerged from observation that OCD symptoms responded to serotonergic medications but not to noradrenergic ones—suggests serotonin system dysregulation in patients with OCD.

Medications : 

Medications High dosages of SSRIs or Clomipramine (TCA) — are first-line OCD medications. However Clomipramine is rarely used. Double-blind clinical trials have found: Clomipramine, Fluoxetine, Sertraline, Paroxetine, Fluvoxamine, Citalopram (Not FDA approved)

SSRIs : 

SSRIs Clomipramine Fluoxetine Fluvoxamine Paroxetine Sertraline Drug Starting dose 25 mg / day 20 mg /day 50 mg / day 20 mg / day 50 mg / day Target dosage (adults) 150 to 200 mg / d 150 to 200 mg / d 150 to 300 mg / d 60 to 80 mg/d 40 to 60 mg / d * 10- to 12-week medication trials at target doses; sequential trials may be required to achieve treatment response.

Side effects : 

Side effects Sedation Insomnia GI side effects Sexual dysfunction. Clomipramine is rarely used as a first-line agent because of its anticholinergic side effects.

Non Response : 

Non Response 10 to 12 weeks at target dosages. Sequential medication trials may be needed to achieve a response. Complete remission is rare, and relapse rates are high when medication is discontinued.22 Up to 40% of patients who do not respond to SSRI, require alternate strategies:

When augmenting an SSRI : 

When augmenting an SSRI Adding Clomipramine, 25 to 50 mg/d, is a reasonable choice. Fluoxetine or paroxetine can inhibit clomipramine metabolism by cytochrome P-450 (CYP) 2D6, with potential for cardiac arrhythmias or seizures. Sertraline or fluvoxamine are less likely to elevate clomipramine levels.

Augmentations : 

Augmentations Fluvoxamine, is most, compatible with clomipramine because it inhibits CYP 1A2—the enzyme that demethylates clomipramine to its inactive desmethyl metabolite, thereby preserving more of the active parent compound. Augmentation’s success may depend in part on a patient’s co-morbidities. Eg. clonazepam may be particularly helpful for children with co-morbid panic symptoms.

Augmentations : 

Augmentations SSRI + low-dose atypical antipsychotic. Risperidone - 1 to 2 mg bid. Olanzapine - 5 to 10 mg/d. Effective even in patients without a comorbid psychotic or tic disorder.23,24 Trials using atypicals as adjunctive therapy for OCD have been brief (12 weeks), and long-term use of these medications carries a risk of metabolic side effects such as weight gain, diabetes, and hyperlipidemia.

Augmentation : 

Augmentation Venlafaxine - 225 mg/d or higher, showed efficacy in a naturalistic study of patients who did not respond to SRIs.25

Augmentation : 

Augmentation Pindolol Lithium Buspirone Trazodone Tryptophan Thyroid hormone has shown mixed results.24


FACTORING IN COMORBIDITIES Acute risk?: Suicidal risk and Self-mutilating behaviors, for instance, must be addressed before a patient can engage in ERP therapy. Active psychosis also would exclude ERP and may be best handled by augmenting with an antipsychotic.17


FACTORING IN COMORBIDITIES Interference with CBT?: Treat Substance abuse and alcohol first. Exposure therapy can exacerbate symptoms in patients who self-medicate their anxiety with alcohol or other substances. In turn, alcohol or other substance abuse may interfere with habituation by ameliorating the anxiety necessary for effective exposure therapy.


FACTORING IN COMORBIDITIES Depression: Could be secondary to their OCD symptoms and may spontaneously decrease with successful OCD treatment. Patients with mild to moderate depression can usually engage in and benefit from ERP without depression specific interventions.


FACTORING IN COMORBIDITIES Patients with comorbid depression may not respond to OCD interventions as well as non-depressed OCD patients do.26 For concurrent OCD and Major depression, expert consensus guidelines suggest combining CBT with an SSRI.17


OTHER COMORBIDITIES OCD + PTSD responded poorly to ERP. Exposure therapy reduced OCD symptoms but increased PTSD symptoms in some patients.27 (one study). Some Axis II disorders Schizotypal, Avoidant, Paranoid, and Borderline personality disorder — have also been found to predict poorer outcome in patients treated with clomipramine.3


OTHER COMORBIDITIES Concurrent treatment? In PTSD with OCD: Preliminary evidence suggests that treatment can or should be simultaneous rather than sequential.27 Likewise, CBT can be used to treat OCD concurrent with other anxiety disorders with only slight modifications, such as:

Concurrent treatment : 

Concurrent treatment Constructing exposures for SAD, at least initially, which minimize extraneous social contact. For panic disorder pts: Treating Anxiety management skills first, so that exposures do not trigger anxiety attacks and reinforce their fears.

Concurrent treatment : 

Concurrent treatment Depression with anxiety: Same medications. OCD + Bipolar disorder: as the antidepressants used to treat OCD can induce mania or hypomania and worsen the mood disorder.28 In these patients, stabilize mood before starting an antidepressant.

Summary : 

Summary OCD is a special kind of anxiety disorder. Circuits are intermixed. Take care of acute risk first. Substance abuse treatment gets first priority. Treat the bigger co-morbid disease first. Give pt tools to manage anxiety. CBT + SSRI +- Atypicals.

References : 

References Weissman MM, Bland RC, Canino GJ, et al. The cross national epidemiology of obsessive-compulsive disorder: The Cross National Collaborative Group. J Clin Psychiatry 1994;55(suppl 3):5–10. Overbeek T, Schruers K, Vermetten E, Griez E. Comborbidity of obsessive-compulsive disorder and depression: Prevalence, symptom severity, and treatment effect. J Clin Psychiatry 2002;63(12):1106–12. Baer L, Jenike MA, Black DW, Treece C. Effects of Axis II diagnosis on treatment outcome with clomipramine in 55 patients with obsessive compulsive disorder. Arch Gen Psychiatry 1992;49(11):862–6. Rasmussen SA, Eisen JL. The epidemiology and clinical features of obsessive compulsive disorder. Psychiatr Clin North Am 1992;15(4):743–58. Rubenstein CS, Pigott TA, L’Heureux F, et al. A preliminary investigation of the lifetime prevalence of anorexia and bulimia nervosa in patients with obsessive compulsive disorder. J Clin Psychiatry 1992;53(9):309–14. Perugi G, Akiskal HS, Pfanner C, et al. Clinical impact of bipolar and unipolar affective comorbidity on obsessive compulsive disorder. J Affect Disord 1997;46(1):15–23. March J, Frances A, Kahn D, Carpenter D. Expert consensus guidelines: treatment of obsessive compulsive disorder. J Clin Psychiatry 1997;58(suppl 4):1–72. Foa EB, Liebowitz MR, Kozak MJ, et al. Randomized, placebo-controlled trial of exposure and response prevention, clomipramine, and their combination in the treatment of obsessive compulsive disorder. Am J Psychiatry 2005;162(1):151–61. Kozak MJ, Liebowitz MR, Foa EB. Cognitive behavior therapy and pharmacotherapy for OCD: The NIMH-sponsored collaborative study.In: Goodman W, Rudorfer M, Maser J (eds). Obsessive compulsive disorder: Contemporary issues in treatment. Mahwah, NJ: Lawrence Erlbaum Associates,2000;501:30. Brown TA, DiNardo PA, Barlow DH.  Anxiety Disorders Interview Schedule for DSM-IV. New York: Graywind Publications, 1994. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The MiniInternational Neuropsychiatric Interview (M.I.N.I): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(suppl 20):22–33. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: I. Development, use, and reliability. Arch Gen Psychiatry 1989;46(11):1006M–11. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: II.Validity. Arch Gen Psychiatry 1989;46(11):1012–6. Foa EB, Huppert JD, Leiberg S, et al. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess 2002;14(4):485–96.

References : 

References First MB, Spitzer RL, Gibbon M, Williams JBW.  Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition New York: New York State Psychiatric Institute, Biometrics Research Department, 1996. Scahill L, Riddle M, McSwiggin-Hardin M, et al. Children’s Yale-Brown Obsessive-Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry 1997;36(6):844–52. Frances A, Docherty JP, Kahn DA. Treatment of obsessive compulsive disorder. J Clin Psychiatry 1997;58(suppl 4):5–72. Foa EB, Franklin ME. Psychotherapies for obsessive-compulsive disorder: A review.In: Maj M, Sartorius N, Okasha A, Zohar J (eds). Obsessive-Compulsive Disorder New York: Wiley,2000;93:115. Abramowitz JS, Foa EB, Franklin ME. Exposure and ritual prevention for obsessive-compulsive disorder: Effect of intensive versus twice weekly sessions. J Consult Clin Psychol 2003;71(2):394–8. Franklin ME, Abramowitz JS, Kozak MJ, et al. Effectiveness of exposure and ritual prevention for obsessive-compulsive disorder: Randomized compared with nonrandomized samples. J Consult Clin Psychol 2000;68(4):594–602. Graybiel A, Rauch SL. Toward a neurobiology of obsessive compulsive disorder. Neuron 2000;28:343–7. Pigott TA, Seay S. Pharmacology of obsessive compulsive disorder: overview and treatment-refractory strategies.In: Goodman MK, Rudorfer MV, Maser JD (eds). Obsessive compulsive disorder: contemporary issues in treatment Mahwah, NJ: Lawrence Erlbaum Associates,2000;277:302. McDougle CJ, Epperson CN, Pelton GH, et al. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 2000;57(8):794–801. Hollander E, Bienstock CA, Koran LM, et al. Refractory obsessive-compulsive disorder: state-of-the-art treatment. J Clin Psychiatry 2002;63(suppl 6):20–9. Hollander E, Friedberg BS, Wasserman S, et al. Venlafaxine in treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2003;64(5):546–50. Abramowitz JS, Foa EB. Does major depressive disorder influence outcome of exposure and response prevention for OCD? Behavior Ther 2001;31(4):795–800. Gershuny BS, Baer L, Jenike MA, et al. Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive-compulsive disorder. Am J Psychiatry 2002;159(5):852–4. Perugi G, Toni C, Frare F, et al. Obsessive-compulsive-bipolar comorbidity: a systematic exploration of clinical features and treatment outcome. J Clin Psychiatry 2002;63(12):1129–34.