Ketamine Treatment for Pediatric-Refractory Obsessive-Compulsive Disorder (OCD)

Condition(s) targeted: Obsessive-Compulsive Disorder

Intervention: Ketamine (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: New York State Psychiatric Institute

Official(s) and/or principal investigator(s):
Moira Rynn, M.D., Principal Investigator, Affiliation: Columbia University/NYSPI

Overall contact:
Moira Rynn, M.D., Phone: (646) 774-5805, Email: RynnM@nyspi.columbia.edu

This pilot study is proposed to determine the acceptability, feasibility and potential efficacy of ketamine, a medication that modulates glutamate in the brain, as a rapid treatment for obsessive-compulsive disorder (OCD) symptoms in adolescents and young adults with OCD. This study will recruit 5 youth (ages 14-20) who are diagnosed with clinically significant OCD and have failed at least two adequate trials of Serotonin Reuptake Inhibitor (SRI) medications and a course of Cognitive-Behavioral Therapy (CBT) for OCD in the past. Participants will receive a single infusion of intravenous ketamine and be assessed at regular intervals post-infusion for up to 14 days. At the end of the 14-day treatment phase, all participants will be offered three months of open treatment for OCD with medication and/or CBT.

Official title: Ketamine Treatment for Pediatric-Refractory Obsessive-Compulsive Disorder (OCD)

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Yale-Brown Obsessive Compulsive Scale, Child version (CYBOCS)

Clinical Global Impressions Scale (CGI-S)

Secondary outcome:

OCD Visual Analogue Scale (OCD-VAS)

Yale-Brown Obsessive Compulsive Challenge Scale (YBOCCS)

Detailed description: See Brief Summary for description.

Minimum age: 14 Years. Maximum age: 20 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Participant must be 14-20 years of age at the time of consent (post-pubertal) 2. Participant and a parent/guardian must be able to read and understand English 3. Participant must be physically healthy and weigh at least 25kg. If female, must not be pregnant. 4. Participant must fulfill DSM-V criteria for OCD, OCD being the principal disorder (i. e., currently the most severe and in need of treatment) and have had OCD for at least six months. 5. Participant must score ≥ 16 on the Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS) prior to entering the study, report at least moderate severity of obsessions and/or compulsions.. 6. Participant must have tried and failed at least two adequate trials of SRI medications and a course of CBT unless the participant is unable to tolerate CBT treatment.

- In order to meet criteria for having had at least two adequate trials of SRI

medication, participants must have been on a stable and minimal adequate dose of at least two SRI medications as defined by the literature for at least 12 weeks, and have a documented history of intolerable adverse effects at a higher dose as evaluated by the study psychiatrist and are therefore unable to increase the dose or complete the full 12 weeks, or have refused further SRI trials. Congruent with the literature, the range of minimally adequate doses to treat OCD are as follows: Clomipramine (Anafranil) 75-100 mg/day; Fluoxetine (Prozac) 20-60 mg/day; Paroxetine or Paroxetine CR (Paxil) 20-40 mg/day; Sertraline (Zoloft) 50-100 mg/day; Fluvoxamine (Luvox) 100-200 mg/day; Citalopram (Celexa) 20-40 mg; Escitalopram (Lexapro) 10-20 mg/day for a minimum of 12 weeks.

- In order to meet criteria for having had an adequate course of CBT for OCD,

patients should have received at least 8 sessions of Exposure and Response Prevention Therapy (EX/RP) by a licensed clinician trained in doing CBT for OCD. A CBT expert on our team will ensure that the clinician administering these exposures has had adequate training and experience in providing this treatment. 7. Participant is off all psychotropic and other types of drugs likely to interact with glutamate for at least 14 days before starting the study. One exception is short acting benzodiazepines for distressing anxiety or insomnia (which can be taken up to 24 hours prior to ketamine infusion). Participants will be off neuroleptics for 1 month and off fluoxetine for 6 weeks prior to the study. 8. For participants younger than 18, written informed assent by the participant and consent by the parent. For participants 19 and older, written consent by the participant and permission for legal guardian/parent to provide information. Exclusion Criteria: 1. Family history of psychosis or substance abuse/dependence. 2. History of violence 3. Presence of psychotic symptoms or lifetime diagnosis of schizophrenia including any auditory or visual hallucinations or presence of delusional thinking, bipolar disorder, substance-induced psychotic disorder, psychosis due to general medical condition. 4. Severely depressed patients with the Children's Depression Rating Scale (CDRS) ≥ 60 or judged clinically to be at risk of suicide. 5. Current diagnosis of an eating disorder. 6. Current or past history of PTSD or significant trauma. 7. Current or past diagnosis of substance abuse/dependence. 8. Current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS). This will be defined by the following criteria: abrupt onset of OCD symptoms (often with comorbid tics) with a relapsing-remitting symptom course, a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection, association with neurological abnormalities during exacerbations (adventitious movements, motoric hyperactivity, urinary hesitancy), and prepubertal age of onset. 9. Participants planning to commence cognitive-behavioral therapy during the period of the study or those who have begun CBT within 8 weeks prior to enrollment. 10. Documented history of hypersensitivity or intolerance to ketamine. 11. Female participants who are either pregnant or nursing or female participants of child bearing age who are sexually active and not taking hormonal birth control. 12. History of significant medical condition that might increase the risk of participation. This would include hypertension (BP > 140/90), chronic congestive heart failure, tachyarrhythmias, myocardial ischemia, intracranial mass lesions, head injury, globe injuries, or hydrocephalus. 13. Concurrent use of any medications that might increase the risk of participation. This would include: St. John's Wort, Tramadol or atracurium, due to potential adverse drug-drug interactions. 14. Positive urine screen for illicit drugs 15. Inability of participant or parent/guardian to read or understand English. 16. Documented history of adverse reaction to anesthesia.

Moira Rynn, M.D., Phone: (646) 774-5805, Email: RynnM@nyspi.columbia.edu

New York State Psychiatric Institute/Columbia University, New York City, New York 10032, United States; Recruiting
Dylan Braun, B.A., Phone: 646-774-5713, Email: braundy@nyspi.columbia.edu
Moira A Rynn, M.D., Principal Investigator

Related publications:

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Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000 Nov;28(2):343-7. Review.

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Rodriguez CI, Bender J Jr, Marcus SM, Snape M, Rynn M, Simpson HB. Minocycline augmentation of pharmacotherapy in obsessive-compulsive disorder: an open-label trial. J Clin Psychiatry. 2010 Sep;71(9):1247-9. doi: 10.4088/JCP.09l05805blu.

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Rynn M, Puliafico A, Heleniak C, Rikhi P, Ghalib K, Vidair H. Advances in Pharmacotherapy for Pediatric Anxiety Disorders. FOCUS: The Journal of Lifelong Learning in Psychiatry. June 2011;9(3): 299-310.

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Finkel JC, Pestieau SR, Quezado ZM. Ketamine as an adjuvant for treatment of cancer pain in children and adolescents. J Pain. 2007 Jun;8(6):515-21. Epub 2007 Apr 16.

Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, Flood P, Simpson HB. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013 Nov;38(12):2475-83. doi: 10.1038/npp.2013.150. Epub 2013 Jun 19.

Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4.

Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64.

Marcus RJ, Victoria BA, Rushman SC, Thompson JP. Comparison of ketamine and morphine for analgesia after tonsillectomy in children. Br J Anaesth. 2000 Jun;84(6):739-42.

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Pediatric OCD Treatment Study (POTS) Team. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. JAMA. 2004 Oct 27;292(16):1969-76.

Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006 Jul;11(7):622-32. Epub 2006 Apr 4. Review. Erratum in: Mol Psychiatry. 2006 Aug;11(8):795.

Correll CU. Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. J Clin Psychiatry. 2008;69 Suppl 4:26-36. Review.

Papolos DF, Teicher MH, Faedda GL, Murphy P, Mattis S. Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype. J Affect Disord. 2013 May;147(1-3):431-6. doi: 10.1016/j.jad.2012.08.040. Epub 2012 Nov 30.

Starting date: March 2015
Last updated: April 16, 2015