Intranasal Esketamine Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder with Comorbid Major Depressive Disorder: A Case Series of Eight Patients

Background: Intranasal esketamine has gained attention as a rapidly acting intervention for treatment-resistant depression, and there is growing interest in its potential anti-obsessional effects. To our knowledge, no published case series has focused on intranasal esketamine in patients with both treatment-resistant obsessive–compulsive disorder (TR‑OCD) and comorbid major depression (MD). Methods: We present eight adult cases at Bellvitge University Hospital who met criteria for TR‑OCD with comorbid MD and received intranasal esketamine augmentation between summer 2023 and 2024. Eligibility required inadequate response to at least two adequate SSRI trials, clomipramine plus one pharmacological augmentation strategy, Y‑BOCS ≥24, and MADRS ≥35. Esketamine was administered intranasally at 56–84 mg per session according to standard protocol for 12 weeks. Response for OCD was defined as ≥35% reduction from baseline Y‑BOCS; depression response as ≥50% reduction from baseline MADRS; depression remission as MADRS ≤10 at endpoint. Results: The mean MADRS score decreased from 37.5±3.8 at baseline to 19.8±13.3 at Week 12 (t(7)=4.55, p=0.0026), reflecting a 48.8% improvement. Y‑BOCS scores declined from 30.1±4.8 to 21.3±8.0 (t(7)=4.16, p=0.0042), a 30.4% reduction. Four participants (50.0%) achieved depression response, of whom two (25.0%) achieved remission; three participants (37.5%) met the OCD response criterion. Conclusions: Esketamine augmentation may exert dual efficacy in reducing both depressive and obsessive–compulsive symptoms in TR‑OCD with comorbid MD. Prospective controlled trials are warranted to confirm these preliminary findings, refine dosing and frequency, and evaluate the role of concurrent psychotherapy in sustaining gains.