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Antipsychotics for Obsessive-Compulsive Disorder: Weighing Risks Vs Benefits

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Savvy Psychopharmacology Antipsychotics for obsessive-compulsive disorder: Weighing risks vs benefits Taylor Modesitt, PharmD, Traci Turner, PharmD, BCPP, Lindsay Honaker, DO, Todd Jamrose, DO, Elizabeth Cunningham, DO, and Christopher Thomas, PharmD, BCPS, BCPP r. E, age 37, has a 20-year history uncontrollable, recurrent thoughts or urges of obsessive-compulsive disorder (obsessions) as well as actions (compulsions) M (OCD), with comorbid generalized in response to those thoughts and/or urges. anxiety disorder and hypertension. His medica- OCD symptom severity is commonly mea- tion regimen consists of lisinopril, 40 mg/d, to sured using the Y-BOCS, a 10-item clinician- control his blood pressure, and escitalopram, rated scale. The Y-BOCS score ranges from 0 40 mg/d, for OCD and anxiety symptoms, which to 40, with higher scores indicating greater Vicki L. Ellingrod, he started taking 12 weeks ago. Mr. E also has severity of symptoms. First-line treatment for PharmD, FCCP completed cognitive-behavioral therapy (CBT) OCD includes selective serotonin reuptake Department Editor with Exposure Response Prevention (ERP) inhibitors (SSRIs) and CBT. The use of anti- therapy for his OCD symptoms. Although esci- psychotics for treating OCD is indicated in talopram and CBT have reduced Mr. E’s OCD treatment guidelines (Box,1-3 page 48) and has symptoms, he still exhibits obsessions, such as been the subject of multiple studies.1-4 fear of contamination, and compulsions, includ- ing handwashing, that are time-consuming Efficacy and cause significant social and occupational The 2013 National Institute for Health distress. His Yale-Brown Obsessive Compulsive Care and Excellence Evidence Update Scale (Y-BOCS) score is 24. Mr. E asks his psychia- included a 2010 Cochrane Review of 11 trist if there is anything else that may provide randomized controlled trials (RCTs) of benefit. He is started on risperidone, 0.5 mg at bedtime, in addition to his existing medications. Practice Points After 8 weeks of treatment with risperidone, • In patients with a partial response to Mr. E’s Y-BOCS score decreases to 21. selective serotonin reuptake inhibitors (SSRIs) and/or cognitive-behavioral therapy (CBT), American Psychiatric OCD, a chronic illness with a prevalence of Association guidelines recommend that approximately 1% to 2%, is characterized by augmentation may be preferable to Dr. Modesitt is PGY-2 Psychiatric Pharmacy Resident, Dr. Turner switching treatments. is Clinical Pharmacy Specialist, and Dr. Honaker is Staff Psychiatrist, Chillicothe VA Medical Center, Chillicothe, Ohio. Dr. Jamrose is Staff • Assessing the potential harms related Psychiatrist, Appalachian Behavioral Healthcare, Athens, Ohio. to the use of antipsychotics in treating Savvy Psychopharmacology Dr. Cunningham is Associate Program Director, Community Health obsessive-compulsive disorder (OCD) is is produced in partnership Network Psychiatry Residency Program, Indianapolis, Indiana. complicated, because this information is with the College Dr. Thomas is Director, PGY-1 and PGY-2 Residency Programs, Clinical of Psychiatric Pharmacy Specialist in Psychiatry, Chillicothe VA Medical Center, not always assessed in trials. and Neurologic Chillicothe, Ohio, and is Clinical Associate Professor of Pharmacology, Pharmacists Ohio University College of Osteopathic Medicine, Athens, Ohio. • Although most evidence supports using cpnp.org Exposure Response Prevention (ERP) over mhc.cpnp.org (journal) Disclosures The contents of this article do not represent the views of the U.S. antipsychotics for treating OCD symptoms Department of Veterans Affairs or the United States Government. that have not responded to SSRIs, ERP This material is the result of work supported with resources and poses its own challenges that may limit the use of facilities at the Chillicothe Veterans Affairs Medical clinical utility. Current Psychiatry Center in Chillicothe, Ohio. Vol. 17, No. 2 47 Savvy Psychopharmacology Box Antipsychotics for OCD: What the guidelines recommend he 2013 American Psychiatric Association medication is discontinued. If the patient has T(APA) obsessive-compulsive disorder a partial response to ERP, intensification of (OCD) treatment guidelines include therapy also can be considered based on recommendations regarding the use of patient-specific factors. In non-responders, antipsychotics in patients who do not switching therapies may be necessary. respond to first-line treatment with selective Alternative treatments including a different serotonin reuptake inhibitors (SSRIs) and/or SSRI; an antidepressant from a difference cognitive-behavioral therapy (CBT). The APA class, such as clomipramine or mirtazapine; recommends evaluating contributing factors, an antipsychotic; or CBT. including comorbidities, family support, and The 2006 National Institute for Health ability to tolerate psychotherapy or maximum and Clinical Excellence guidelines for OCD recommended drug doses, before augmenting recommend additional high-intensity CBT, Clinical Point or switching therapies.1 adding an antipsychotic to an SSRI or In patients with a partial response to clomipramine, or combining clomipramine In patients with a SSRIs and/or CBT, the APA suggests that with citalopram in non-responders. There is no augmentation may be preferable to switching guidance regarding the order in which these partial response to treatments. Augmentation strategies for treatments should be trialed. Antipsychotics SSRIs and/or CBT, SSRIs include antipsychotics or CBT with are recommended as an entire class, and there Exposure Response Prevention (ERP); are no recommendations regarding dosing or the APA suggests augmentation strategies for CBT include long-term risks. These guidelines are based that augmentation SSRIs. Combining SSRIs and CBT may on limited evidence, including only 1 trial of decrease the chance of relapse when quetiapine and 1 trial of olanzapine.2,3 may be preferable to switching treatments antipsychotics as adjunctive treatment to there was a significant difference between SSRIs.5 All trials were <6 months, and most groups (n = 80, 2 RCTs, OR 0.27; 95% CI 0.09 were limited regarding quality aspects. to 0.87; effect size d = 0.27 [0.09, 0.87]). Two trials found no statistically signifi- Adjunctive treatment with risperidone cant difference with olanzapine in efficacy was superior to antidepressant mono- measures (Y-BOCS mean difference [MD] therapy for participants without a signifi- −2.96; 95% confidence interval [CI] −7.41 cant response in OCD symptom severity of to 1.22; effect size d = −2.96 [−7.14, 1.22]). at least 25% with validated measures (OR Among patients with no clinically signifi- 0.17; 95% CI 0.04 to 0.66; effect size d = 0.17 cant change (defined as ≤35% reduction in [0.04, 0.66]), and in depressive and anxi- Y-BOCS), there was no significant difference ety symptoms. Mean reduction in Y-BOCS between groups (n = 44, 1 RCT, odds ratio scores was not statistically significant with [OR] 0.76; 95% CI 0.17 to 3.29; effect size risperidone (MD −3.35; 95% CI −8.25 to d = 0.76 [0.17, 3.29]). Studies found increased 1.55; effect size d = −3.35 [−8.25, 1.55]).5 weight gain with olanzapine compared with antidepressant monotherapy. A 2014 meta-analysis by Veale et al3 Statistically significant differences were included double-blind, randomized trials demonstrated with the addition of que- that examined atypical antipsychotics com- Discuss this article at tiapine to antidepressant monotherapy as pared with placebo for adults with OCD www.facebook.com/ shown in Y-BOCS score at endpoint (Y-BOCS that used an intention-to-treat analysis. CurrentPsychiatry MD −2.28; 95% CI −4.05 to −0.52; effect Unlike the Cochrane Review, these stud- size d −2.28 [−4.05, −0.52]). Quetiapine ies used the Y-BOCS as a primary outcome also demonstrated benefit for depressive measure. Participants had a Y-BOCS score and anxiety symptoms. Among patients of ≥16; had at least 1 appropriate trial of an with no clinically significant change SSRI or clomipramine (defined as the maxi- Current Psychiatry 48 February 2018 (defined as ≤35% reduction in Y-BOCS), mum dose tolerated for at least 8 weeks); Savvy Psychopharmacology and had to continue taking the SSRI or OCD severity (16 to 23). Those with higher clomipramine throughout the trial, which baseline Y-BOCS scores had a larger effect was a duration of at least 4 weeks. Of 46 size for risperidone and quetiapine.3 published antipsychotic papers that were Two studies included in the meta- identified, 20 were excluded and 12 were analysis classified OCD symptoms by sub- duplicates. The primary reason for trial type, such as by dimensions of checking; exclusion was open-label study design. symmetry, ordering, counting, and repeat- Fourteen articles were included in the ing; contamination and cleaning; and meta-analysis, but all had small sample hoarding. Currently, no clinically signifi- sizes and no long-term follow-up data.3 cant predictor of outcome of antipsychotic Antipsychotics in the meta-analysis included therapy has been identified. Two studies risperidone (4 studies), quetiapine (5 stud- included in the meta-analysis assessed ies), olanzapine (2 studies), aripiprazole (2 patients with comorbid tic disorders and Clinical Point studies), and paliperidone (1 study). found no difference by treatment. One A 2015 study found no The overall difference in Y-BOCS score study demonstrated benefit of haloperi- change between drug and placebo groups dol in patients with comorbid tic disorders
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