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Revised Mar 1, 2008 Obsessive Compulsive Disorder (OCD): Medication Guide for Primary Care Physicians Compiled by Michael Cheng, MD, FRCP(C) Note that there is also an accompanying family handout: “Obsessive Compulsive Disorder: Information for Families” (available from http://www.drcheng.ca) Disclaimer The content of this document is for general information and education only. The accuracy, completeness, adequacy, or currency of the content is not warranted or guaranteed. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should always seek the advice of physicians or other qualified health providers with any questions regarding a health condition. Any procedure or practice described here should be applied by a health professional under appropriate supervision in accordance with professional standards of care used with regard to the unique circumstances that apply in each practice situation. The authors disclaim any liability, loss, injury, or damage incurred as a consequence, directly or indirectly, or the use and application of any of the contents of this document. This work is “licensed” under a Creative Commons License (Attribution-Non Commercial-Sharelike 2.0, http://creativecommons.org/licenses/by-nc-sa/2.0/) which means that you are free to copy, distribute, display and perform the work, and make derivative works as long as you give the original author credit, the work is not used for commercial purposes, and if you alter, transform, or build upon this work, you may distribute the resulting work only under a license identical to this one. Where to Get this Handout This handout is available from http://www.drcheng.ca in the Mental Health Information section. Any comments and suggestions are welcome and will help ensure this handout is helpful. 1 of 8 Table of Contents Sequence of Treatment ...........................................................................................................2 Medication Treatment for OCD .................................................................................................2 Duration of Treatment .............................................................................................................5 Second-Generation Antidepressants: Dosing in Children and Adolescents ...................................3 If SSRI monotherapy is insufficient ..........................................................................................4 Addendum: PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection) ...........................................................................................................5 Overview of Treatment Strategies for OCD ...............................................................................7 References .............................................................................................................................8 Treatment Guidelines ..............................................................................................................8 Sequence of Treatment For mild to moderate OCD in children and youth, it is usually felt best to commence with nonmedication interventions: Specific anti-OCD interventions such as Cognitive Behavioral Therapy (CBT) General health interventions such as ensuring adequate sleep, adequate diet General coping interventions such as stress management, i.e. identifying sources of stress (e.g. with school, work, family, relationships), and using conflict resolution or problemsolving to deal with stresses Medication Treatment for OCD Medication can be helpful for OCD that is causing severe distress, or for OCD that has not responded sufficiently to non-medication interventions: Start with any single SSRI agent, which includes: Fluoxetine, Fluvoxamine, Sertraline, Paroxetin, Citalopram (Geller’s 2003 meta-analysis suggested it doesn’t matter which SSRI one starts with) Due to controversy about self-harm, it might be simpler to not start a patient on Paroxetine On the other hand, if you have a patient who is doing well on Paroxetine, do not necessarily feel you have to automatically discontinue their medication. If they are doing well, consider obtaining informed consent, and continuing them on the medication. 2 Second-Generation Antidepressants: Dosing in Children and Adolescents Many children and teenagers may require adult dosages of medications, due to their metabolism. Note that (as with adult conditions), many psychiatric medications are prescribed ‘off-label’ as not every medication use has been fully documented with clinical trials. (Note that in general, over 60% of all medications prescribed are felt to be used ‘off-label’). Agent Fluoxetine (Prozac) Sertraline (Zoloft) Fluvoxamine (Luvox) Paroxetine (Paxil) Citalopram (Celexa) Comments FDA approval: Major Depression, OCD (age 7-17) Start at 5 mg daily for child; 10 mg daily for adolescent Target dosage range 20-60 mg daily, aim for higher end dosage for OCD Maximum 80 mg daily FDA approval: OCD (age 6-18) Start at 25 mg daily for child; 50 mg daily for adolescent Target dosage range 50-200 mg daily, aim for higher end dosage for OCD Maximum 200-300 mg daily FDA approval: OCD (age 6-18) Start at 25 mg daily for child; 25-50 mg daily for adolescent Target dosage 25-200 mg daily, aim for higher end dosage for OCD Maximum 300 mg daily Note: although FDA is currently recommending against its use in major depressive disorder in youth, note Geller’s recent positive study in JACAAP Nov 2004 journal showing efficacy in OCD in youth Start 5-10 mg q daily Target dosage 20-40 mg daily, aim for higher dosage for OCD Maximum 60 mg daily FDA: FDA Approval for OCD No official indication for children/adolescents, though used off-label Start 10 mg q daily for child; 10 mg daily for adolescent Target dosage 10-40 mg daily, aim for higher end dosage for OCD Maximum 60 mg daily Source: Adapted from Bostic et al, 2003. Retrieved Oct 3, 2003 from http://www.psychiatrictimes.com/p030988.html 3 If SSRI monotherapy is insufficient If there is poor response despite monotherapy with an SSRI, then other options include: Switching to Clomipramine (Anafranil) Clomipramine (Anafranil), supplied in 10, 25, 50 mg tablets In children aged 10 to 17 years, an initial dose of 25 mg/day is recommended. Dosage may be increased by 25 mg increments, as tolerated, at 3 to 4 day intervals. By the end of 2 weeks, patients may be titrated up to 100 to 150 mg/day or 3 mg/kg, whichever is lower. Thereafter, the dose may be gradually increased to 200 mg or 3 mg/kg whichever is lower. Maximum dosage 200 mg daily for children or adolescents. Augmentation – evidence in adults supports adding a second agent (which by itself is not felt to be a primarily anti-OCD agent) in order to provide a synergistic anti-OCD effect. Typically, medication dosages for an augmenting agent tend to be on the lower dosage range for that agent. Typical augmenting agents reported for OCD include: Dopamine antagonists (i.e. antipsychotics), particular if patient has comorbid tics, such as: Risperidone (0.5-3 mg daily): double-blind, placebo controlled studies in adults showing efficacy (Hollander et al., 2003). Olanzapine (5-10 mg daily): double-blind, placebo controlled studies in adults showing efficacy (Bystritsky et al., 2004). Quetiapine (using up to 300 mg daily): double blind study in adults (Denys D et al., 2004) Psychostimulant: possible efficacy for Dextroamphetamine (but Methylphenidate) suggested by Joffe et al., 1991; Insel et al., 1983. Pindolol (7.5 mg/day): double-blind, placebo controlled studies showing efficacy (Dannon et al., 2000). Naltrexone (Revia) at 25-50 mg daily reported as anecdotally helpful. Mood stabilizer: Lithium has been reported to augment imipramine, clomirpamine, desipramine and doxepin, however double-blind studies have not shown overwhelming success with lithium augmentation in OCD. Buspirone (Buspar) reported as being helpful in open trials, but not in double-blind studies. Eicosapentaenoic acid (EPA) (an Omega 3 fatty acid) has been reported anecdotally as being helpful, but of note, Fux failed to find any additional benefit using adjunctive EPA (Fux et al., 2004) not for 4 Novel-agent strategies Second-messenger systems: Inositol shown helpful in six-week, double-blind, controlled crossover trial (Fux et al., Am. J. Psychiatry, 1996). Topiramate (Topamax) Open study in 2004 by Dr. Michael Van Ameringen, n=16 adults, showed 70% of patients had improvement with mean dosage of Topiramate 250 mg/day added for 14-16 weeks to SSRI therapy (abstract, not yet published) Dual therapy with two serotonin agents Duration of Treatment for at least 1-year Daniel Pine recommends that after at least 1-year of remission of symptoms, one can consider stopping the medication during the first low stress period that occurs. (For students, this low stress period usually means the summer, as opposed to during the school year). When the decision has been made to stop, the medication should be tapered down gradually (e.g. reduce by 25% of the dosage per week, so that a medication can thus be stopped over a month or so) until completely stopped. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection) In about <5% of cases of OCD in children, it is felt that a contributory medical condition causing OCD symptoms is PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). It is characterized by sudden onset or exacerbation of OCD symptoms in the presence of streptococcal upper respiratory tract infections. The mechanism is believed to be caused by antineuronal antibodies formed against group, beta-hemolytic streptococcal cell wall antigens, which cross-react with caudate neural tissue with the consequence of initiation of obsessive-compulsive symptoms. The official criteria for PANDAS, as established in 1998 by Dr. Susan Swedo1 from the NIMH are: presence of obsessive-compulsive disorder, tic disorder, or both; with prepubertal onset; sudden, severe symptom onset and an episodic course characterized by remissions and abrupt exacerbations; a link in time between either the symptom onset or exacerbation and a GABHS infection; adventitious movements or clumsiness. The following suggestions have been cited for children who may appear to be vulnerable to PANDAS: 1 Treat all streptococcal infections aggressively with antibiotics Be sure to complete the course of antibiotic treatment to avoid development of resistant strains of bacteria. Retrieved Nov 4, 2006 from http://www.medscape.com/viewarticle/547096?rss 5 Make use of proven therapies such as cognitive/behavioral therapy and serotonin medication (SSRI's) as are utilized to treat the more usual forms of OCD. Diagnostic investigations recommended include throat culture for streptococcus, antistreptolysin O titer (ASOT) and anti-streptococcal DNase B titer. Consult a neurologist if you suspect PANDAS 6 Overview of Treatment Strategies for OCD Mild to Moderate OCD Psychotherapy (e.g. Cognitive-Behavioral Therapy) or Psychosocial Interventions Moderate to Severe OCD If unsatisfactory response In addition to Psychotherapy, also consider medications Medication Strategies Start with any of the following SSRIs for children/youth (Fluoxetine, Fluvoxamine, Sertraline, Paroxetine, Citalopram) If unsatisfactory response Consider Clomipramine If unsatisfactory response Consider Augmentation with antipsychotic, stimulant, pindolol, naltrexone, lithium Switching to alternate monotherapy Dual therapy with two serotonin agents 7 References Bystritsky A, Ackerman DL, Rosen RM, Vapnik T, Gorbis E, Maidment KM, et al.: Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial. J Clin Psychiatry, 2004 Apr;65(4):5658. Christopher M: Update on pharmacologic management of OCD: agents and augmentation, J. Clin. Psychiatry 1997;58(suppl 12): 11-17. Denys D, de Geus F, van Megan HJ, Westenberg, HG. A double-blind, randomized, placebocontrolled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors. J Clin Psychiatry 2004;65:1040-8. Fux et al.: A placebo-controlled cross-over trial of adjunctive EPA in OCD. J Psychiatr Res. 2004 May-Jun;38(3):323-5. Geller et al.: Which SSRI? A Meta-Analysis of Pharmacotherapy Trials in Pediatric ObsessiveCompulsive Disorder, Am J Psychiatry 160:1919-1928, November 2003 http://ajp.psychiatryonline.org/cgi/content/abstract/160/11/1919 Kaplan A, Hollander E: A review of pharmacologic treatments for obsessive-compulsive disorder, Psychiatric Services, August 2003, 54(8): 1111-1118. Soomro GM, et al "Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD) (Review)" Cochrane Database of Systematic Reviews 2008; Issue 1: DOI: 10.1002/14651858.cd001765.pub 3. Tynan WD: Obsessive Compulsive Disorder, last updated May 16, 2005, retrieved May 16, 2005 from http://www.emedicine.com/ped/topic2794.htm Treatment Guidelines and Interesting Reviews See http://www.psychguides.com for the Expert Consensus Guideline Series on the Treatment of OCD See http://www.aacap.org for the Practice Parameters of the Treatment of OCD in Children and Youth. As of July 16, 2005, the direct link is at http://www.aacap.org/clinical/parameters/summaries/Ocdsum.htm Geller’s metanalysis, 2003 For the four serotonin reuptake inhibitors (SSRIs) of paroxetine (Paxil), fluoxetine (Prozac), fluvoxamine (Luvox) and sertraline (Zoloft), all these four SSRIs were equivalent in efficacy In comparing efficacy of those four SSRIs to clomipramine (Anafranil), clomipramine was superior – however, it still cannot be recommended as first-line due to a higher risk of adverse effects with clomipramine 8