1. Obsessive-Compulsive Disorder: Pharmacotherapy
Flavio Guzman, MD

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

3. 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

4. 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

5. 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),

6. Medications used for OCD

7. SRIs
SSRIs
Clomipramine
Trial of efficacy: weeks

8. 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.

9. 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

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

11. 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.

12. 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),

13. Sertraline More robust efficacy seen with doses closer to 200 mg
Doses of 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.

14. 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):

15. 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:

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

17. 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.

18. Practical considerations

19. 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

20. 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.

21. 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.

22. Treatment resistance / Augmentation

23. 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),

24. 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),

25. 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),

26. Augmentation options Augmentation Pharmacological treatments
Psychotherapy
Other somatic treatments

27. 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),

28. 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),

29. End of presentation