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.

See Brief Summary for description.

Inclusion Criteria:

1. Participant must be 14-22 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 one adequate trial of SRI medications or clomipramine and a course of CBT unless the participant is unable to access or tolerate CBT treatment.

   • In order to meet criteria for having had at least one adequate trial of SRI medication, participants must have been on a stable and minimal adequate dose of at least one SRI medication or clomipramine 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. The exceptions are SRI medications and 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.

Adverse event data was collected during the ketamine infusion and for two hours post-infusion. Following the infusion, adverse events were assessed daily for a period of 14 days and at a 3-month follow-up visit.