Intranasal Esketamine Augmentation in Treatment-Resistant Obsessive–Compulsive Disorder with Comorbid Treatment-Resistant Depression: A Six-Month Case Report

Background: Evidence for repeated intranasal esketamine in obsessive–compulsive disorder (OCD) remains preliminary, particularly when OCD co-occurs with treatment-resistant depression (TRD). Methods: We report a 58-year-old woman treated with intranasal esketamine in routine clinical care for TRD; change in obsessive–compulsive symptoms was followed as a secondary observational outcome. Her history aligned with the eligibility framework of a 2026 prospective intranasal esketamine series: primary Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) OCD, baseline Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score of 33, a comorbid major depressive episode with a Montgomery–Åsberg Depression Rating Scale (MADRS) score of 38, sequential inadequate response to two high-dose selective serotonin reuptake inhibitor (SSRI) trials, clomipramine 250 mg/day for 6 months, eight cognitive-behavioral therapy (CBT) sessions incorporating exposure and response prevention (ERP), and brexpiprazole augmentation. The CBT/ERP course was time-limited and did not overlap with esketamine. Esketamine was administered at 56 mg initially and 84 mg thereafter, twice weekly for 4 weeks, weekly in month 2, and every 2 weeks during months 3–6. Results: MADRS/Y-BOCS scores were 23/18 at month 1, 19/15 at month 3, and 17/14 at month 6, corresponding to reductions of 55.3% and 57.6%. The OCD response threshold was met from month 1 and the depression response threshold from month 3. Adverse effects were transient and required no medical intervention or treatment discontinuation. Conclusions: During 6 months of routine-care intranasal esketamine augmentation for TRD, obsessive–compulsive improvement accompanied antidepressant improvement. The observation is hypothesis-generating and cannot distinguish a direct anti-obsessional effect from improvement related to depression, ongoing oral treatment, repeated clinical contact, or other nonspecific factors.