PS
Psychiatry

Obsessive-Compulsive Disorder

October 21, 2013.
John H. Greist, MD,

Educational Objectives

The goal of this program is to improve diagnosis and management of obsessive-compulsive disorder (OCD). After hearing and assimilating this program, the clinician will be better able to:

1. Describe manifestations of obsessing and ritualizing and their impact on the lives of patients with OCD.

2. Reduce time spent obsessing and ritualizing through the use of medications and cognitive behavioral therapy.

3. Augment pharmacotherapy to improve symptoms or address treatment resistance in patients with OCD.

Summary

Background: lifetime prevalence 2.5%; runs waxing and waning course; onset typically at ≈20 yr of age (earlier in men than in women); homogenous themes — worries and concerns about harm, risk, or danger; feeling of incompleteness (ie, not having done something satisfactorily); subtypes — heterogenous (patients can obsess over anything)

Comorbidity in OCD: rule rather than exception; depression most common comorbid condition (patients with OCD have two-thirds lifetime risk of developing major depressive disorder [3-4 times greater than general population]); increased prevalence of other anxiety disorders

Obsessions: unwanted and intrusive ideas, images, and impulses associated with profound distress; patients may describe obsessions as senseless, goofy, dumb, stupid, crazy, insane, irrational, or asinine; distress results in compulsive actions intended to lessen obsessions, most typically through repetitive, purposeful behavioral rituals (eg, hand washing, checking locks or stoves, ritualistic thinking or counting)

Yale-Brown Obsessive Compulsive Scale (Y-BOCS): 10 items (5 for obsessions; 5 for rituals or compulsions); items — time spent obsessing or ritualizing; interference; distress from obsessions; distress individuals would experience if rituals prevented; resistance to obsessions and rituals; success when resisting; score — 0 to 4 points for each item (depends on severity); total score ranges from 0 to 40; with total score of 30, adults typically stop working and children stop going to school; with total score ≤10, patients typically feel and function quite well; most patients who seek treatment score between 20 and 29

Typical case: first treatment typically at 31 yr of age (11 yr after average age of onset); patient (age 20 yr) with typical Y-BOCS score of 25 spends ≤7 hr/day obsessing and ritualizing; after treatment, reduction of Y-BOCS score to 17 limits obsessing and ritualizing to 4 hr/day; if patient treated from onset, >12,000 hr (1.375 yr) saved over 11 yr; extremely few patients cured of OCD, but many can be helped substantially

Pharmacotherapy: clomipramine, fluoxetine, fluvoxamine, paroxetine, and sertraline approved for adults with OCD (all approved for children and adolescents except paroxetine); all selective serotonin reuptake inhibitors (SRIs) show equal efficacy (effect size 0.45-0.70); clomipramine (tricyclic antidepressant) has effect size of 1.48 (from large registration trials submitted to Food and Drug Administration [FDA] for approval); these patterns consistent in children and adolescents (from meta-analysis of >10,000 participants in 12 placebo-controlled double-blinded studies [Gellar et al, 2003]); some individuals have similar or superior responses with selective SRIs compared with clomipramine; selective SRIs have fewer side effects, greater safety in overdose, and used as first-line treatment

Dosing: flat dose-response curve seen with OCD (as well as depression) for all approved selective SRIs; tendency to prescribe excessive doses of well-tolerated selective SRIs for OCD results in more side effects; start at low dose and wait for tolerance of side effects to develop; after improvements plateau, dosages may be increased; decrease dosage if no further improvement; with effective treatment, patients must stay on medication to maintain benefits; 89% of patients relapse to baseline levels within 7 wk after discontinuation of clomipramine; studies of fluoxetine and fluvoxamine found half-doses preserved majority of efficacy, whereas stopping medication eliminated nearly all benefits

Other monotherapies: most data from open trials with small population sizes; no FDA-approved options

Inositol (Fux et al, 1996): randomized, cross-over design; 13 patients received inositol 18 g/day or placebo for 6 wk each; Y-BOCS score decreased by 9 points with inositol (compared to 1 point with placebo)

St. John’s wort (Taylor and Kobak, 2000): open trial with 8 participants for 9 wk; Y-BOCS scores decreased by 7 points; however, in subsequent placebo-controlled trial with 60 participants enrolled for 12 wk, St. John’s wort showed no advantage over placebo

Venlafaxine: potent SRI at high doses; however, placebo-controlled double-blind trial had negative results; paroxetine-controlled trial showed no difference in efficacy; found inferior to clomipramine

Augmentation of SRIs: pro-serotonergic approaches using tryptophan, fenfluramine, lithium, or buspirone may be effective in select individuals, but have failed to surpass placebo in controlled trials; limited evidence supports combining SRIs

Haloperidol (McDougle et al, 1994): added after 12 wk of treatment with fluvoxamine in patients with Y-BOCS score of 25 or 26; individuals with multiple motor tics or Gilles de la Tourette syndrome clearly benefited from comparatively small doses of haloperidol; other patients showed no improvement

Risperidone (McDougle et al, 2000): all SRIs included; mean dose 2.2 mg; 50% of patients had Y-BOCS scores reduced by ≥8 points (not predicted by presence of tics)

Olanzapine and quetiapine: efficacy supported by limited evidence (mostly from open-label trials); due to significant side effects associated with antipsychotics, take extreme caution with long-term use; no antipsychotic approved for augmentation of SRIs; atypical antipsychotics may exacerbate symptoms of OCD in patients with schizophrenia

Combinations of SRIs: clomipramine plus fluvoxamine — best studied; fluvoxamine inhibits pathways for metabolism of clomipramine, and thus increases blood levels of clomipramine and decreases levels of its metabolite (desmethylclomipramine); addition of fluvoxamine improved poor response to clomipramine in patients with depression or OCD (Szegedi et al, 1996); citalopram plus clomipramine (Pallanti et al, 1999) — 16 participants with poor response to either medication underwent 90-day trial of citalopram alone or citalopram plus clomipramine; monotherapy reduced Y-BOCS score by 6 points; combination reduced score by 18 points; side effects mild to moderate in both groups

Glutamate: in patients with OCD, increased glutamate found in cerebrospinal fluid and prefrontal cortex and striatum; glutamate antagonists should theoretically augment SRIs in patients with inadequate response; riluzole (Coric et al, 2005) — FDA-approved for amyotrophic lateral sclerosis; open-augmentation trial for patients with OCD who failed to respond to SRIs; riluzole 100 to 200 mg/day used for 6 to 12 wk in profoundly treatment-refractory patients with baseline Y-BOCS score of 31; riluzole reduced mean score to 18 points

Other augmentation

Inositol (Fux et al, 1999): failed to show improvement over placebo as augmentation for SRIs

Cognitive behavioral therapy (CBT): in study comparing CBT to clomipramine, Y-BOCS score decreased by 5.3 with medication alone, 10.8 with CBT alone, and 12.1 with combination; in Pediatric OCD Treatment Study (POTS), Y-BOCS score decreased by 3.3 with sertraline alone, 8.3 with CBT alone, and 8.9 with combination; addition to SRI therapy (Simpson, 2008) — after 64 wk on adequate dose of SRI, patients had Y-BOCS score of 26; randomization to 8-wk augmentation with stress management training, relaxation, deep breathing, or exposure (to triggers of discomfort) and ritual prevention; stress management training decreased Y-BOCS score to 17, and exposure and ritual prevention to 14 (effect size 1.31 [≥0.8 considered large]); 30 hr of CBT self-administered and therapist-coached

Exposure and ritual prevention: leads to habituation; patients can adjust to annoying triggers; effective but not widely available; free through computer program by Jazz Pharmaceuticals; randomized controlled trial of computerized therapy and 12 hr of therapist-directed CBT produced equal 8-point improvements in Y-BOCS scores, compared to 2 points with relaxation (used as control); single session of exposure and ritual prevention reduced Y-BOCS score by 6 points (9 points with ≤20 sessions; 13 points with ≥20 sessions)

Other treatment modalities: electroconvulsive therapy — not recommended for OCD unless used for severe or psychotic depression, or as alternative to neurosurgery; vagus nerve stimulation (VNS) — in study of VNS in 7 patients with no response to multiple SRIs and >19 hr of CBT, Y-BOCS score decreased from 30 to 25 at 6 mo; VNS well-tolerated; neurosurgery — used for decades to treat OCD; study found mean Y-BOCS score decreased to 22 after 12 mo when prospective anterior cingulotomy (some bilateral) performed on patients with mean Y-BOCS score of 35 (Kim et al, 2003); deep brain stimulation (DBS) — rapidly supplanting neurosurgery; in study of 26 individuals who failed to respond to ≥1 SRI, clomipramine, augmentation with antipsychotics, and ≥20 hr of CBT, DBS reduced Y-BOCS score from 34 to 21 at 36 mo; studies of DBS had more adverse events compared to neurosurgery

Conclusions: CBT has greatest short-term effects, without high relapse rates after discontinuation (possibly since patients learn to self-administer therapy); SRIs effective if continued; augmentation helpful to some individuals through trial and error; surgery can be life-saving for patients with most severe OCD

Readings

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Greist receives grant/research support from AstraZeneca, Eli Lilly and Company, Forest Laboratories, and Janssen Pharmaceuticals; and is on the Speakers’ Bureau for Novo Nordisk. The planning committee reported nothing to disclose. In this lecture, Dr. Greist presents information that is related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

PS422001

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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