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

Summary

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 6 youth (ages 14-22) who are diagnosed with clinically significant OCD and have failed at least one adequate trial of a Serotonin Reuptake Inhibitor (SRI) medication and a course of Cognitive-Behavioral Therapy (CBT) (unless unable to access or tolerate) 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.

Timeline

Start

2015-03

Primary completion

2018-02-21

Completion

2020-07-31

Outcome

Missed primary endpoint

registry analysis (superiority test); Ketamine Treatment Group; p = .20; Mean Difference (Final Values) 1.53 (95% CI -2.27 to 7.87); t-test, 2 sided NCT02422290 ↗

registry analysis (superiority test); Ketamine Treatment Group; p = .18; Mean Difference (Final Values) 1.63 (95% CI -.56 to 2.16); t-test, 2 sided NCT02422290 ↗

Publications

• Background Rauch SL, Wedig MM, Wright CI, Martis B, McMullin KG, Shin LM, Cannistraro PA, Wilhelm S. Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder. Biol Psychiatry. 2007 Feb 1;61(3):330-6. doi: 10.1016/j.biopsych.2005.12.012. Epub 2006 Feb 21.
• Background Atmaca M, Yildirim H, Ozdemir H, Tezcan E, Poyraz AK. Volumetric MRI study of key brain regions implicated in obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jan 30;31(1):46-52. doi: 10.1016/j.pnpbp.2006.06.008. Epub 2006 Jul 20.
• Background Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000 Nov;28(2):343-7. doi: 10.1016/s0896-6273(00)00113-6. No abstract available.
• Background Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology. 2005 Sep;30(9):1735-40. doi: 10.1038/sj.npp.1300733.
• Background Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry. 2000 Sep;39(9):1096-103. doi: 10.1097/00004583-200009000-00008.
• Background 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.
• Background Coric V, Milanovic S, Wasylink S, Patel P, Malison R, Krystal JH. Beneficial effects of the antiglutamatergic agent riluzole in a patient diagnosed with obsessive-compulsive disorder and major depressive disorder. Psychopharmacology (Berl). 2003 May;167(2):219-20. doi: 10.1007/s00213-003-1396-z. Epub 2003 Mar 26. No abstract available.
• Background Stewart SE, Jenike EA, Hezel DM, Stack DE, Dodman NH, Shuster L, Jenike MA. A single-blinded case-control study of memantine in severe obsessive-compulsive disorder. J Clin Psychopharmacol. 2010 Feb;30(1):34-9. doi: 10.1097/JCP.0b013e3181c856de.
• Background Hezel DM, Beattie K, Stewart SE. Memantine as an augmenting agent for severe pediatric OCD. Am J Psychiatry. 2009 Feb;166(2):237. doi: 10.1176/appi.ajp.2008.08091427. No abstract available.
• Background Rynn M, Puliafico A, Heleniak C, Rikhi P, Ghalib K, Vidair H. Advances in pharmacotherapy for pediatric anxiety disorders. Depress Anxiety. 2011 Jan;28(1):76-87. doi: 10.1002/da.20769.
• Background Kararmaz A, Kaya S, Turhanoglu S, Ozyilmaz MA. Oral ketamine premedication can prevent emergence agitation in children after desflurane anaesthesia. Paediatr Anaesth. 2004 Jun;14(6):477-82. doi: 10.1111/j.1460-9592.2004.01224.x.
• Background Dahmani S, Michelet D, Abback PS, Wood C, Brasher C, Nivoche Y, Mantz J. Ketamine for perioperative pain management in children: a meta-analysis of published studies. Paediatr Anaesth. 2011 Jun;21(6):636-52. doi: 10.1111/j.1460-9592.2011.03566.x. Epub 2011 Mar 29.
• Background 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. doi: 10.1016/j.jpain.2007.02.429. Epub 2007 Apr 16.
• Background 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.
• Background 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. doi: 10.1016/s0006-3223(99)00230-9.
• Background 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. doi: 10.1001/archpsyc.63.8.856.
• Background 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. doi: 10.1093/oxfordjournals.bja.a013585.
• Background Aspinall RL, Mayor A. A prospective randomized controlled study of the efficacy of ketamine for postoperative pain relief in children after adenotonsillectomy. Paediatr Anaesth. 2001 May;11(3):333-6. doi: 10.1046/j.1460-9592.2001.00676.x.
• Background 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. doi: 10.1001/jama.292.16.1969.
• Background 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. doi: 10.1038/sj.mp.4001823. Epub 2006 Apr 4.
• Background 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.
• Background 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.
• Ishimuro HS, Yanes-Lukin PK, Goldberg PH, Simpson HB, Rynn MA. Ketamine Treatment for Pediatric Refractory Obsessive: Five Open Label Cases. J Child Adolesc Psychopharmacol. 2025 Apr;35(3):167-170. doi: 10.1089/cap.2024.0127. Epub 2025 Feb 3.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ketamine	Small molecule	0.5 mg/kg	Intravenous

Indications