Obsessive-Compulsive Disorder: Pharmacotherapy Flavio Guzman, MD

Overview General concepts Using SSRIs and clomipramine for OCD Practical considerations Treatment resistance / Augmentation

Use scales for rating the severity of OCD Y-BOCS Y-BOCS II Florida Obsessive Compulsive Inventory (FOCI) American Psychiatric Association (2013).Guideline Watch: Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder. Washington, DC. American Psychiatric Press

Defining treatment response in OCD trials Y-BOCS score: 25-35% or greater decrease Clinical Global Impressions-Improvement (CGI-I) score of: 1 (very much improved) 2 (much improved) American Psychiatric Association (2013).Guideline Watch: Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder. Washington, DC. American Psychiatric Press

General concepts What percentage of patients improve? 40-60% How much do they improve? 20-40 % reduction in their symptoms Pigott, T. A., & Seay, S. M. (1999). A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder. Journal of Clinical Psychiatry. Jefferson, J. W., Kobak, K. A., Katzelnick, D. J., & Serlin, R. C. (1995). Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder: a meta-analysis. Archives of General psychiatry, 52(1), 53-60.

Medications used for OCD

SRIs SSRIs Clomipramine Trial of efficacy: 10-12 weeks

Not approved, but efficacious: SSRIs for OCD Generally considered equally effective Higher doses are frequently used FDA-approved for OCD: Fluvoxamine Fluoxetine Paroxetine Sertraline Not approved, but efficacious: Citalopram Escitalopram Hudak, R. & Dougherty, D. (2011). Clinical obsessive-compulsive disorders in adults and children. Cambridge New York: Cambridge University Press.

Fluvoxamine 250 - 300 mg/day Average dose: Earlier onset Allows more rapid dose titration CR formulation approved in 2008: American Psychiatric Association (2013).Guideline Watch: Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder. Washington, DC. American Psychiatric Press

Fluvoxamine CYP1A2 inhibitor CYP3A4 inhibitor Greater potential for DDI Luvox CR (Fluvoxamine CR) [Prescribing Information]. Palo Alto, CA: Jazz Pharmaceuticals, Inc. Accessed Sep 2014

Fluoxetine More benefit in OCD: 40-60 mg/day Fluoxetine: 2 to 4 days Norfluoxetine: 7 to 15 days Hudak, R. & Dougherty, D. (2011). Clinical obsessive-compulsive disorders in adults and children. Cambridge New York: Cambridge University Press.

Paroxetine Advantage Studied for long-term effectiveness Disadvantages CYP2D6 interactions AISD More benefit in OCD: 40-60 mg/day Hollander, E., et al (2003). Acute and long-term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine. The Journal of clinical psychiatry, 64(9), 1113-1121.

Sertraline More robust efficacy seen with doses closer to 200 mg Doses of 250-400 mg/day: additional benefit Ninan, P. T., et al (2006). High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial. Journal of Clinical Psychiatry. Hudak, R. & Dougherty, D. (2011). Clinical obsessive-compulsive disorders in adults and children. Cambridge New York: Cambridge University Press.

Citalopram - Escitalopram Not FDA-approved Evidence from several open label trials One RCT demonstrated citalopram efficacy at all dosages (20,40, 60 mg), trend for greater efficacy at the 60 mg dosage Montgomery, S. A., et al. "Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder."International clinical psychopharmacology 16.2 (2001): 75-86.

Citalopram Advantage: Disadvantage: Less potential for DDI FDA recommends a maximum citalopram dose of 40 mg/day In geriatric patients the maximum should be 20 mg/day FDA safety information Citalopram – Accessed online: http://1.usa.gov/1kC0jOg

Clomipramine Tolerability: blockade of H1, M1, alpha 1 receptors and Na channels Metabolized to an active metabolite by demethylation via CYP1A2 Fluvoxamine inhibits CYP1A2

Clomipramine for OCD Clomipramine dose: 200-250 mg/day Does clomipramine perform better than SSRIs? Meta-analyses: Larger effect size for clomipramine than SSRIs (compared with placebo( Not based on head-to head comparisons Head-to-head comparison trials: Mixed results Hudak, R. & Dougherty, D. (2011). Clinical obsessive-compulsive disorders in adults and children. Cambridge New York: Cambridge University Press.

Practical considerations

Recommendations for the acute phase CBT (ERP) alone: Not too depressed, anxious or severely ill to cooperate SRI alone: Previously responded Not able to cooperate with the demands of CBT CBT (ERP) + SRI More effective than monotherapy Not necessary for all patients American Psychiatric Association (2007). Practice Guidelines for the treatment of Patients with Obsessive Compulsive Disorder. Washington, DC. American Psychiatric Press American Psychiatric Association (2013).Guideline Watch: Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder. Washington, DC. American Psychiatric Press

How to choose a specific medication Choice not based on efficacy (SSRIs and clomipramine considered to be equally efficacious) Based on: Side effects profile Comorbid condition Family history of response Potential for drug-drug interactions Hudak, R. & Dougherty, D. (2011). Clinical obsessive-compulsive disorders in adults and children. Cambridge New York: Cambridge University Press.

How to dose Starting dose: Titrate to highest tolerated dose Typically not different than for other indications Start lower if comorbid PD or GAD Titrate to highest tolerated dose Usually titrated weekly Adequate trial of efficacy 10-12 weeks on highest tolerated dose Hudak, R. & Dougherty, D. (2011). Clinical obsessive-compulsive disorders in adults and children. Cambridge New York: Cambridge University Press.

Treatment resistance / Augmentation

Treatment resistance What percentage do not show adequate response ? 40-60% No standard definition of treatment resistance Arumugham, S. S., & Reddy, J. Y. (2013). Augmentation strategies in obsessive compulsive disorder. Expert Review of Neurotherapeutics, 13(2), 187-203.

Treatment resistance, according to most studies: Y-BOCS score: Less than 25-35% reduction Failure to respond Trial of 12 weeks Not having a (CGI-I) score of: 1 (very much improved) 2 (much improved) Arumugham, S. S., & Reddy, J. Y. (2013). Augmentation strategies in obsessive compulsive disorder. Expert Review of Neurotherapeutics, 13(2), 187-203.

Strategies for non-responding patients If no response to initial trial of SSRI Switching to a different SSRI If no response to two SSRIs Switching to clomipramine Partial response to treatment with an SSRI Poor response to multiple SSRIs Augmentation Arumugham, S. S., & Reddy, J. Y. (2013). Augmentation strategies in obsessive compulsive disorder. Expert Review of Neurotherapeutics, 13(2), 187-203.

Augmentation options Augmentation Pharmacological treatments Psychotherapy Other somatic treatments

Antipsychotic augmentation First choice Risperidone Next options Aripiprazole Haloperidol Use at moderate doses Risperidone 2 mg/day Arumugham, S. S., & Reddy, J. Y. (2013). Augmentation strategies in obsessive compulsive disorder. Expert Review of Neurotherapeutics, 13(2), 187-203.

Other options More evidence required: Not effective 5HT3 antagonists Glutamatergic drugs Topiramate Not effective Buspirone Lithium Clonazepam Arumugham, S. S., & Reddy, J. Y. (2013). Augmentation strategies in obsessive compulsive disorder. Expert Review of Neurotherapeutics, 13(2), 187-203.

End of presentation