Anxiety Disorders

1. Anxiety Disorders Sarah Melton, PharmD,BCPP,CGP Director of Addiction Outreach Associate Professor of Pharmacy Practice Appalachian College of Pharmacy Oakwood, VA

2. Objectives • Given a case example, evaluate whether the patient meets DSM-IV-TR criteria for an anxiety disorder [generalized anxiety disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD)]. • Interpret common rating scales in the evaluation and management of anxiety disorders. • Distinguish differences in pharmacology, kinetics, efficacy, dosing, adverse effects, and drug interactions of benzodiazepines in the management of anxiety disorders. • Compare the efficacy, dosing, and adverse effects of the serotonergic antidepressants, and the role of antipsychotics in the management of anxiety disorders.

3. Objectives • Evaluate whether patient and professional education is optimal to facilitate safe and effective drug therapy for anxiety disorders. (DII) • Using practice guidelines, develop a pharmacotherapy plan, including dosing and duration of therapy, and nonpharmacologic treatments, for a patient with anxiety disorders. • Discuss the role of pharmacotherapy in the management of anxiety disorders in special populations (e.g., children, elderly patients and pregnancy). • Resolve potential drug-related problems in patients with anxiety disorders.

4. Epidemiology of Anxiety Disorders • As a group - most frequently occurring psychiatric disorders • Over the past decade, prevalence has not changed, but rate of treatment has increased. • Patients are frequent users of emergency medical services, at high risk for suicide attempts, and substance abuse. • Costs for anxiety disorders represent one-third of total expenditures for mental illness. • In primary care, often underdiagnosed or recognized years after onset. • Median age of onset: GAD: 31 years SAD: 13 years OCD: 19 years PTSD: 23 years PD : 24 years • Lifetime prevalence: GAD: 5.7% SAD: 12.1% OCD: 1.6% PTSD: 6.8% PD: 4.7% WFSBP Guidelines for the Pharmacological Treatment of Anxiety, Obsessive Compulsive , and Post-Traumatic Stress Disorders- First Revision (2008), Data from the National Comorbidity Survey Replication(2005)

5. Treatment Plan • Patient preference • Severity of illness • Comorbidity • Concomitant medical illness • Complications like substance abuse or suicide risk • History of previous treatments • Cost issues • Availability of treatments in given area

6. Patient Education • Mechanisms underlying psychic and somatic anxiety should be explained. • Describe typical features of the disorder, treatment options, adverse drug effects. • Explain advantages and disadvantages of the drug: • Delayed onset of effect • Activation syndrome or initial jitteriness with SSRIs/SNRIs

7. Duration of Drug Treatment • Anxiety disorders typically have a waxing and waning course. • After treatment response, which often occurs much later in PTSD and OCD, treatment should continue for at least 12 months to reduce the risk of relapse.

8. Dosing • In RCTs, SSRIs and SNRIs have a flat response curve with the exception of OCD • 75% of patients respond to the initial (low) dose • In OCD, the dose must usually be pushed to maximally tolerated dosages • In elderly patients, treatment should be started with half the recommended dose or less to minimize adverse effects • Patients with panic disorder are very sensitive to serotonergic stimulation and often discontinue treatment because of initial jitteriness • Antidepressant doses should be increased to the highest recommended level if the initial low or medium dose fails

9. Dosing • Controlled data on maintenance treatment are scarce • Continue the same dose as in the acute phase • For improved compliance, administer medications in a single dose if supported by half-life data • Benzodiazepine doses should be as low as possible, but as high as necessary • In hepatic impairment, dose should be adjusted

10. Monitoring Treatment Efficacy • Use of symptom rating scales: • Panic and Agoraphobia Scale (PAS) • Hamilton Anxiety Scale (HAM-A) • Liebowitz Social Anxiety Scale (LSAS) • Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) • Clinician-Administered PTSD Scale (CAPS) • Scales are time-consuming and require training • Clinical Global Impression (CGI) or specific self-report measures may suffice in busy settings

11. Treatment Resistance • Many patients do not fulfill response criteria after initial treatment • Commonly used threshold for response is ≥ 50% improvement in total score of commonly used rating scale • Review diagnosis, assess for adherence, maximally tolerated dosages, sufficient trial period, assess for comorbidities • Change the dose or switch to another medication? • If no response after 4-6 weeks (8-12 weeks in OCD or PTSD), then switch medication • If partial response, reassess in 4-6 weeks • Issue of switching vs. augmentation is debated by experts and not clearly defined in the literature

12. Non-pharmacological Treatment • Psychoeducation is essential • Disease state, etiology, and treatment options • Effect sizes with psychological therapies are as high as the effect sizes with medications • Exposure therapy and response prevention • Agoraphobia, social anxiety, OCD, PTSD • Cognitive Behavioral Therapy – most evidence to support in all disorders • Response is delayed, usually later than medications • Prolonged courses are needed to maintain treatment response • Some evidence to show that treatment gains are maintained over time longer than medications • Expensive, not readily available in rural or remote areas

13. Selective Serotonin Reuptake Inhibitors (SSRIs) • First-line drugs for all anxiety disorders • Dose and education at initiation of therapy is important • Restlessness, jitteriness, insomnia, headache in the first few days/weeks of treatment may jeopardize compliance • Lower starting doses reduces overstimulation • Adverse effects include headache, fatigue, dizziness, nausea, anorexia • Weight gain and sexual dysfunction are long-term concerns • Discontinuation syndrome: paroxetine • Anxiolytic effect is delayed 2-4 weeks (6-8 weeks in PTSD, OCD)

14. Selective Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) • Efficacy of venlafaxine and duloxetine in certain anxiety disorders has been shown in controlled studies • Early adverse effects such as nausea, restlessness, insomnia and headache may limit compliance • Sexual dysfunction long-term • Modest, sustained increase in blood pressure may be problematic • Significant discontinuation syndrome with venlafaxine occurs, even with a missed dose • Antianxiety effects have latency of 2-4 weeks

15. Tricyclic Antidepressants (TCAs) • Efficacy in all anxiety disorders is well-proven, except in SAD • Imipramine, clomipramine have most evidence • Adverse effects: initially increased anxiety, anticholinergic, cardiovascular, sedation, impaired cognition, decreased seizure threshold, elevated LFTs (clomipramine) • Weight gain, sexual dysfunction are problematic long-term • Discontinuation syndrome • Avoid in elderly, patients with cardiovascular disease, seizure disorders, and suicidal thoughts • Second-line agents because of adverse effects/toxicity • Dosage should be titrated up slowly; onset of effect is 2-6 weeks, longer in OCD

16. MonamineOxidase Inhibitors (MAOIs) • Efficacy of phenelzine established in panic, SAD and PTSD • Last-line agent for treatment resistance; used by experienced psychiatrists • Risk of adverse effects • Life threatening drug and food interactions • Patient education on dietary restrictions and drug interactions imperative • Give doses in the morning and mid-day to avoid overstimulation and insomnia

17. Benzodiazepines • Anxiolysis begins in 30-60 minutes after oral or parenteral administration • Safe and effective for short-term use; maintenance requires evaluation of risks vs. benefits • Avoid in patients with history of substance or alcohol abuse • Most commonly used in combination with SSRI/SNRI during first few weeks of therapy • Guideline recommendations: Prescribe on scheduled, not prn basis • Not effective in depression

18. Hydrozyzine • Commonly used in community setting; anxiolytic effects that may be beneficial in treating GAD • There are controlled data supporting efficacy, but up to 40% of patients report adverse effects • This agent was similar to buspirone in anxiolytic effects in a short-term trial • Hydroxyzine is not associated with dependence

19. PREGABALIN Not FDA- approved for anxiety, but used commonly in Europe Effective in acute/long-term GAD and a few trials of SAD Typical doses of 300-600 mg/day Onset of activity was evident after 1 week Adverse effects: dizziness, sedation, dry mouth, psychomotor impairment Pregabalin was not associated with clinically significant withdrawal symptoms when tapered over 1 week ANTICONVULSANTS Not used in routine treatment of anxiety disorders, but may some utility as adjunctive agents in some disorders Carbamazepine, valproate, lamotrigine, and gabapentin have shown efficacy in preliminary studies for PTSD Other Agents

20. Buspirone • Beneficial only in GAD • Adverse Effects • Nausea, headache, dizziness, jitteriness and dysphoria (initial) • Dosing • Initial 5 mg tid up to maximum 60 mg/day • Advantages • Non-sedating • No abuse potential • Disadvantages • No antidepressant effect for comorbid conditions • Initial therapeutic effect delayed by 1-2 weeks, full effects occurring over several weeks • Ineffective in patients who previously responded to benzodiazepines??

21. ATYPICAL ANTIPSYCOTICS Quetiapine was effective as monotherapy for GAD Atypical antipsychotics have been used as adjunctive agents for non-responsive cases of anxiety associate with OCD and PTSD BETA-ADRENERGIC BLOCKERS β - blockers reduce autonomic anxiety symptoms such as palpitations, tremor, blushing However, double-blind studies have not shown efficacy in any disorder Recommended for use in nongeneralized SAD; given before a performance situation Other Agents

22. Differentiating Anxiety Disorders • Many anxiety disorders present similarly • Key to differentiation is rationale behind fear: • Panic attacks occur in both social anxiety and panic disorder • Fear of anxiety symptoms is characteristic of panic disorder • Fear of embarrassment is from social interactions typifies SAD • GAD is likely diagnosis if anxiety about social situations are part of a pattern of multiple worries • Anxiety may also be induced by medications or medical conditions

23. CASE 1 A 70-year-old man presents to his physician complaining of having trouble sleeping, “being nervous all the time,” and feeling like he is “going to lose control.” His wife died 2 years ago and the symptoms have been getting worse since that time. He is retired as an accountant, but lately cannot even concentrate to pay his own bills. He has seasonal allergies, COPD, angina, and Type II diabetes. Medications include albuterol/ipratropium inhaler, theophylline, enalapril, aspirin, metformin, and loratatadine with pseudoephedrine. He smokes 2 ppd (100 pack years). He drinks 8-10 drinks/day that are caffeinated and also drinks 2-3 beers nightly to help him fall asleep and relieve his “stress.” What factors should be considered in the assessment and differential diagnosis of this patient’s anxiety?

24. Substance-Induced Anxiety • CNS Stimulants • CNS depressant withdrawal • Psychotropic medications • Cardiovascular medications • Heavy metals and toxins

25. Anxiety Secondary to Medical Conditions • Endocrine • Addison’s disease • Cushing disease • Hyperthyroidism • Hypoglycemia • Pheochromocytoma • Cardiovascular • Angina, MI • CHF, MVP • Respiratory • Asthma, COPD • Hyperventilation, PE • Metabolic • Porphyria, Vitamin B12 deficiency • Neurologic • CNS neoplasms, chronic pain • Encephalitis, PD, epilepsy • Gastrointestinal • Crohns Disease, PUD • IBS, Ulcerative Colitis • Inflammatory • RA, SLE • Other • HIV, Malignancy McClure EB, Pine DS. (2009). Clinical Features of the Anxiety Disorders. In BJ Sadock, VA Sadock , P Ruiz (Eds.). Kaplan and Sadock’s Comprehensive Textbook of Psychiatry (9th ed, pp. 1844-1855). Philadelphia, PA: Lippincott, Williams and Wilkins.

26. CASE 1 (continued) • Factors that need further investigation before a diagnosis of an anxiety disorder can be made include: • Medical illness (COPD, angina) • Possible depression, adjustment to stressors • Medications/substances • Pseudoepehdrine • Theophylline • Caffeine • Nicotine

27. CASE 2 A 30-year-old woman presents to her PCP c/o of daily headaches, muscle tension, diarrhea and difficulty sleeping. She states that her husband says she is a “worry wart” and she admits that she has difficulty controlling her anxiety over her financial situation, job security, and the safety of her children. She has become irritable because she always “feels on the edge.” The symptoms started 7 months ago, following the death of her sister but she recalls her mother telling her that “she worried too much, just like her father” during her adolescent years. She is employed as an office manager, but has missed several days of work in the past month because of her anxiety, physical symptoms, and inability to concentrate. No significant past medical history and only medications include a multivitamin. PPH: Major Depression 2 years ago treated with fluoxetine 20 mg for 6 months. She is married with 2 children (ages 3 and 6), denies tobacco or alcohol use. Drinks 1 cup of coffee in the morning and an occasional soda in the afternoon.

28. Problem Identification • What symptoms does the patient exhibit that are consistent with Generalized Anxiety Disorder? • What risk factors are present in her history? • What are treatment options?

29. Diagnostic Criteria for GAD • The patient reports having excessive anxiety and worry occurring more days than not for at least 6 months about a number of events of activities (such as work or school performance). • The patient has difficulty in controlling worry. • The anxiety and worry are associated with 3 or more of the following 6 symptoms: • Restlessness or feeling keyed up and on edge • Easily fatigued • Difficulty concentrating, or mind going blank • Irritability • Sleep disturbance (difficulty falling asleep or staying asleep, or restless, unsatisfying sleep) Diagnostic and Statistical Manual of Mental Disorders-IV-TR, 2000.

30. CASE 2 (continued) • Risk Factors for GAD present in case • Gender (female) • Genetic factors (father) • Medication/substance induced (stimulant) • Stressful event (death of sister) • Treatment options • Nonpharmacologic - Psychoeducation, CBT • Pharmacologic (antidepressants, benzodiazepines, buspirone, others)

31. Pharmacological Treatment of GAD • First-line • Recommended daily doses: • Escitalopram 10-20mg Venlafaxine 75-225 mg • Paroxetine 20-50 mg Duloxetine 60-120 mg • Sertraline 50-150 mg • Second-line • Benzodiazepines when patient has no history of dependency; may combine with antidepressants for first 2-4 weeks • Pregabalin 150-600 mg; Imipramine 75-200 mg • Others • Hydroxyzine 37.5-75 mg– effective in trials for acute anxiety, but ADRs limit use • Buspirone 15- 60 mg– indicated for GAD, but efficacy results were inconsistent • Treatment resistance • Augmentation of SSRI with atypical antipsychotic (quetiapine, risperidone or olanzapine) • Quetiapine effective as monotherapy, but not FDA approved for anxiety because of metabolic and cardiac risks associated with chronic use WFSBP Guidelines for the Pharmacological Treatment of Anxiety, Obsessive Compulsive , and Post-Traumatic Stress Disorders- First Revision (2008)

32. CASE 3 A 24-year old college student presents to the student mental health facility for follow-up for treatment of panic disorder with agoraphobia. He presented 5 months ago complaining of attacks of chest pain, SOB, tingling fingers, dizziness, nausea. During the attacks, he felt like he was “outside his body” and “everything was crashing in on him.” He began staying in his apartment nearly all the time and was on the verge of being dismissed from college for not attending classes. He was started on paroxetine 5 mg daily and alprazolam 0.5 mg three times daily. His current doses are paroxetine 40 mg po daily and alprazolam 1 mg in the morning, 1 mg at lunch, and 2 mg at bedtime. He was doing so well that he decided to discontinue the alprazolam yesterday because his mother told him she thought he was “hooked” on it. Today, he feels quite anxious, his heart is racing, and his hands are tremulous. He wonders if he is getting ready to have a full-blown panic attack. What do you recommend at this point in his therapy?

33. Diagnostic Criteria for Panic Disorder • Presence of at least 2 unexpected panic attacks characterized by at least 4 of the following somatic or cognitive symptoms, which develop abruptly and peak within 10 minutes: • Cardiac, sweating, shaking, SOB or choking, nausea, dizziness, depersonalization, fear of loss of control, fear of dying, paresthesias, chills or hot flashes • The attacks are followed by one of the following for 1 month: • Persistent concern about having another attack • Worry about consequences of the attack • Significant change in behavior because of the attack • May occur with or without agoraphobia Diagnostic and Statistical Manual of Mental Disorders-IV-TR, 2000.

34. Panic Attack/Agoraphobia • Panic Attack • About 7% of the population will experience at least one panic attack • Types • Unexpected (uncued) • Situationally bound (cued) • Situationally predisposed • Can occur in the context of another anxiety or mental disorder • Agoraphobia • Anxiety about being in a situation where escape is difficult or help is unavailable in the event of a panic attack • Examples of feared situations: open spaces, trains, tunnels, bridges, crowded rooms • Situations are avoided or endured with significant anxiety about having a panic attack or symptoms • Can persist even after panic attacks abate

35. Panic Disorder - Treatment • Non-pharmacologic Treatment • Avoid trigger substances • Caffeine, OTC stimulants, nicotine, drugs of abuse • CBT • Correct avoidance behavior • Train individual to identify and control signals associated with panic attacks • Efficacy – 80-90% short term

36. Pharmacological Treatment of Panic Disorder • First-line • Recommended daily doses • Citalopram 20-60 mg Paroxetine 20-60 mg • Escitalopram 10-20 mg Sertraline 50-150 mg • Fluoxetine 20-40 mg Venlafaxine 75-225 mg • Fluvoxamine 100–300 mg • Second-line • Imipramine 75-250 mg , clomipramine 75-250 mg • Benzodiazepines when no history of dependency; may combine with antidepressants for first 2-4 weeks for more rapid response and to limit ADRs • Alprazolam 1.5-8 mg/day Diazepam 5-20 mg/day • Clonazepam 1-4 mg/day Lorazepam 2-8 mg/day • Treatment-resistance: phenelzine WFSBP Guidelines for the Pharmacological Treatment of Anxiety, Obsessive Compulsive , and Post-Traumatic Stress Disorders- First Revision (2008)

37. Panic Disorder:Therapeutic Use of Benzodiazepines • Antipanic effect begins within the first week • Effective in 55-75% of panic disorder patients • Effective in patients needing rapid relief of anticipatory anxiety • Breakthrough (interdose rebound) anxiety may occur 3-5 hours after a dose of shorter acting benzodiazepines such as alprazolam • Dependence/withdrawal are associated with long-term use or high dose

38. Benzodiazepines – Pharmacokinetics • Onset of Action • High lipophilicity – fastest absorption = faster onset but also “euporic rush” • Diazepam, clorazepate, alprazolam • Lower lipophilicity = longer onset, less euphoria • Chlordiazepoxide, clonazepam, oxazepam • Duration of Action (t1/2) • Long: diazepam, chlordiazepoxide, clonazepam • Short: alprazolam, lorazepam, oxazepam • Metabolic Pathway • Hepatic microsomal oxidation (Phase I metabolism) • Impaired by aging, liver disease, or meds that inhibit oxidative process • Prolonged half-life, accumulation • Alprazolam, clonazepam, chlordiazepoxide, clorazepate, diazepam • Glucuronide conjugation (Phase II metabolism) • Lorazepam, oxazepam

39. Benzodiazepines: Drug Interactions • Pharmacodynamic • CNS depressants [alcohol, barbiturates, opiates] • Pharmacokinetic • Inhibitors: cimetidine, nefazodone, fluoxetine, fluvoxamine, erythromycin, ketoconazole, oral contraceptives, protease inhibitors, grapefruit juice, isoniazid • Inducers: phenytoin, carbamazepine, phenobarbital, rifampin

40. Benzodiazepines: Dependence and Abuse • Physical dependence • Within 3-4 months, can lead to down-regulation of endogenous GABA production • Withdrawal symptoms common • Rebound anxiety, insomnia, jitteriness, muscle aches, depression, ataxia, blurred vision • Do not stop therapy abruptly – TAPER • Abuse • High risk in patients with substance or alcohol abuse history • Alprazolam, lorazepam, and diazepam

41. Benzodiazepine Withdrawal • Onset, duration and severity varies according to dosage, duration of treatment, and half-life, and speed of discontinuation • Short half-life, withdrawal begins in 1-2 days, shorter duration, more intense • Long half-life, withdrawal begins in 5-10 days, lasts a few weeks • Common symptoms: anxiety, insomnia, irritability, nausea, diaphoresis, systolic hypertension, tachycardia, tremor • Possible consequences: delirium, confusion, psychosis, seizures

42. CASE 3 (Continued) • The patient has had excellent response to pharmacotherapy; however, he has only been treated for 5 months. • Treatment guidelines recommend therapy for at least 1 year after resolutions of symptoms before considering discontinuation • Benzodiazepines are typically used in the first 2-4 weeks as acute therapy, so it is reasonable to consider slowly tapering the alprazolam at this point. • Abrupt discontinuation is not appropriate; he now has withdrawal symptoms that must be addressed, as well as his concern about addiction.

43. Benzodiazepine Discontinuation Typical tapering schedule for benzodiazepines: • 25% per week reduction in dosage until 50% of dose then reduce by one eighth every 4-7 days • Therapy > 8 weeks: taper over 2-3 weeks • Therapy > 6 months: taper over 4-8 weeks • Therapy > 1 year: taper over 2-4 months • For patients on high potency benzodiazepines for monotherapy of panic disorder, a very gradual discontinuation is recommended • Discontinue benzodiazepines slowly over 3-4 months to prevent relapse and emergence of withdrawal symptoms • Alprazolam doses >3 mg/d  by 0.5 mg every 2 weeks until 3 mg, then  by 0.25 mg every 2 weeks until 1 mg, then  by 0.125 mg every 2 weeks • Clonazepam  by 0.125 mg every 2 weeks • Diazepam  by 2.5 mg every 2 weeks • Lorazepam  by 0.5 mg every 2 weeks

44. Diagnostic Criteria for SAD • A marked and persistent fear of one or more social or performance situations involving exposure to unfamiliar people or possible scrutiny by others. The person fears that he or she will act in a way (or show symptoms of anxiety) that will be humiliating or embarrassing • Exposure to the feared social situation provokes anxiety or even a panic attack • The person recognizes that the fear is excessive or unreasonable • Feared social or performance situations are avoided or endured with intense anxiety or distress • The condition interferes significantly with the person's normal routine, occupational (or academic) functioning, or social activities or relationships, or there is marked distress about having the phobia • Specify the disorder as “generalized” if fears include most situations Diagnostic and Statistical Manual of Mental Disorders-IV-TR, 2000.

45. Social Anxiety DisorderTreatment • Early detection and treatment is important • Because of the nature of the illness, patients are reluctant to to seek treatment • Pharmacological and nonpharmacological therapy both effective

46. Social Anxiety DisorderNonpharmacologic Treatment • CBT • Change negative thoughts patterns • Repeated exposure to feared situation • Social skills training • 12-16 weekly sessions, each 60-90 minutes • Workbook with homework exercise • Clinical improvement within 6-12 weeks • Long term gains

47. Pharmacological Treatment of SAD • First-line • Recommended doses: • Escitalopram 10-20 mg Fluoxetine 20-40 mg • Fluvoxamine 100-300 mg Sertraline 50-150 mg • Paroxetine 20-50 mg Venlfaxine 75-225 mg • Second-line • Imipramine 75-200 mg • Clonazepam 1.5-8 mg/day, when patient has no history of dependency; may combine with antidepressants for first 2-4 weeks • Treatment resistance • Addition of buspirone to an SSRI effective in one open study; buspirone not effective as monotherapy. • Phenelzine WFSBP Guidelines for the Pharmacological Treatment of Anxiety, Obsessive Compulsive , and Post-Traumatic Stress Disorders- First Revision (2008)

48. Case 4 A 28-year old woman presents to the Anxiety Disorders Clinic after being referred by her PCP. The patient recently gave birth to a son 2 months ago. Within 2 weeks after delivery, she started having intrusive thoughts of harming her baby. Over and over again, she imagined herself dropping the baby, cutting or burning him. She checks the appliances in the house multiple times to make sure they are cut off because she fears starting a fire that will harm the baby. She will not use the kitchen knives or scissors. She spends 40 minutes every time she goes out checking and re-checking the baby’s car seat, so now she just stays at home. She reports some relief during the day when she knocks on hard objects in 3 sets of 5 knocks. She is so concerned about hurting her baby that she has started avoiding holding him except when nursing. She says that half of her days are consumed with her checking behavior. Past psychiatric history is positive for depression when she was in college that responded well to sertraline. YBOCS score = 32

49. Diagnostic Criteria for OCD • Obsessions • Recurrent and persistent thoughts, impulses or images that are intrusive and cause a great amount of anxiety • These thoughts, impulses, or images are not worries about daily life issues • Patient attempts to ignore or suppress the thoughts, impulses, images, or to neutralize them by applying special thoughts or actions • The thoughts, impulses, or images are recognized as a product of the patient’s mind • Compulsions • Repetitive behaviors that the person feels “compelled” to perform in response to an obsession, or according to rigid self-imposed rules • The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; but are not connected in a realistic or logical way with what they are designed to neutralize or prevent • The person has recognized that the obsessions or compulsions are excessive or unreasonable (this does not apply to children). Diagnostic and Statistical Manual of Mental Disorders-IV-TR, 2000.

50. OCD Comorbidities • Depression (75%) • Anxiety disorders • Tic Disorders (20-30%) • 5-7% have full Tourette’s syndrome • PANDAS (pediatric autoimmune neuropsychiatric disorders) • OCD spectrum disorders • Somatoform disorders (body dysmorphic disorder) • Eating disorders (anorexia, bulimia, binge-eating) • Impulse control disorders (trichotillomania, compulsive nail biting, kleptomania, compulsive buying)