Intranasal Ketamine and Cognitive-Behavioral Therapy for Treatment-Refractory Obsessive-Compulsive Disorder

This report describes a single-case, open-label treatment of a patient (pseudonym AL) with severe, treatment-refractory obsessive–compulsive disorder (OCD) treated with a combination of intensive cognitive–behavioural therapy (CBT) and intranasal ketamine. AL is a Caucasian male in his late 20s whose principal diagnosis was OCD with comorbid major depressive disorder (MDD) with chronic suicidal ideation, social anxiety disorder, and a history of bulimia nervosa. He had an extensive treatment history with multiple pharmacological agents and both residential and outpatient CBT without adequate response; the extracted text notes that detailed dose histories were incomplete for some prior medications. Treatment occurred across 16 weeks: 8 weeks as an inpatient on a psychiatric unit followed by 8 weeks as an outpatient. Intensive CBT was delivered throughout the inpatient stay, with weekday meetings and approximately 1–2 hours of CBT homework daily. Therapy emphasised exposure with response prevention (ERP); it was not manualised. Sessions generally reviewed homework and hierarchies and concluded with therapist-assisted exposures. Some mindfulness exercises and behavioural activation were included but constituted a small portion of therapy time. Intranasal racemic ketamine hydrochloride was added during weeks 3–6 of treatment. Ketamine was given twice weekly at a total dose of 50 mg per administration, delivered as five 10 mg aliquots (5 mg per nostril per aliquot) over 20 minutes using an LMA intranasal atomiser. The medication was used off-label and is not FDA‑approved for OCD. During and after ketamine administration, vital signs were monitored. Symptom severity was tracked with standard clinician-rated instruments: the Yale–Brown Obsessive–Compulsive Scale (YBOCS) for OCD and the Montgomery–Åsberg Depression Rating Scale (MADRS) for depression. Dissociative effects were assessed with the Clinician Administered Dissociative State Scale (CADSS); the extracted text reports baseline and 60‑minute post‑ketamine CADSS values and a t-test comparing them (t(7) = 1.87, p = .10). After discharge, the patient continued outpatient CBT twice weekly for one month and once weekly for an additional month.

Pre-treatment severity was high (YBOCS = 28; MADRS = 33). After two weeks of inpatient CBT but before ketamine initiation, OCD symptoms had reduced modestly to YBOCS = 23; the patient attributed part of this improvement to the absence of many symptom triggers on the inpatient unit. Following initiation of intranasal ketamine, further reductions in OCD severity were observed: after the first week of ketamine the YBOCS decreased to 20, and scores remained relatively stable through the end of the inpatient period. Suicidal ideation declined rapidly after the first ketamine dose and was reported to be nearly absent after the third administration. Dissociative and psychotomimetic effects were described as mild and transient, resolving within one hour of administration. CADSS scores reported in the extracted text indicate a baseline mean of 0 (SD = 0) and a 60‑minute post‑ketamine mean of 2.25 (SD = 3.19); the cited comparison (t(7) = 1.87, p = .10) did not reach conventional statistical significance. Vital signs remained stable during and after ketamine dosing. Clinically, the patient showed a noticeable improvement in ability to engage in response prevention shortly after beginning ketamine, with anecdotal reports of markedly better exposure engagement and homework compliance. After discharge and transition to outpatient CBT, both OCD and depressive symptoms—including suicidal ideation—worsened somewhat, but improved again with continued CBT. The patient continued to experience frequent obsessions and urges but reported reduced distress, improved capacity to dismiss or accept obsessions, better restraint of compulsions (notably delaying), and reduced OCD‑related functional impairment. Depressive symptoms improved relative to baseline but remained severe and at times interfered with ERP.

Adams and colleagues report that intranasal ketamine was well tolerated and temporally associated with further reductions in OCD symptoms, improved engagement with ERP, and a rapid reduction in suicidal ideation in this treatment‑refractory patient. The investigators acknowledge that causal attribution is not possible in a single-case, uncontrolled report. They note several plausible alternative explanations: ongoing intensive inpatient CBT begun prior to ketamine, and the reduced presence of typical obsessive–compulsive triggers while on the inpatient unit. These factors could account for at least part of the clinical improvement observed prior to ketamine administration. Despite these caveats, the study team advances reasons to consider a ketamine contribution: the patient reported additional symptom reduction temporally linked to the start of ketamine, there was a marked and rapid improvement in compliance with response prevention after ketamine began, and suicidality decreased quickly following initial doses. On this basis the authors propose that ketamine might augment extinction‑based psychotherapy such as ERP, potentially by improving patients’ capacity to engage with exposures, and they characterise the case as warranting further investigation. Key limitations acknowledged in the extracted text include the single‑case design, lack of a control condition or component separation (i.e. CBT alone versus ketamine plus CBT), incomplete prior medication dose histories in the report, and the potential confound of the inpatient milieu. The authors recommend component‑controlled trials to determine whether ketamine and ERP have synergistic effects on OCD symptoms and to clarify safety and efficacy in this population. They also note that intranasal racemic ketamine was used off‑label for OCD in this case.