Intranasal Esketamine Augmentation in Treatment-Resistant Obsessive–Compulsive Disorder with Comorbid Treatment-Resistant Depression: A Six-Month Case Report
Tommaso Barlattani, Giorgio Sernia, Chiara D’Amelio, Silvia Maritato, Davide Gabriele, Antony Bologna, Filippo Trebbi, Valerio Ricci, Carmine Tomasetti, Vassilis Martiadis, Fabiola Raffone, Alessandro Rossi, Francesca Pacitti, Domenico de Berardis
Psychiatry International September 10, 2026 DOI: 10.3390/psychiatryint7050207 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case study Case report Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | A 58-year-old woman with treatment-resistant depression and comorbid obsessive-compulsive disorder |
| Intervention | Esketamine |
| Dose | 56 mg initially and 84 mg thereafter |
| Duration | 6 months (twice weekly for 4 weeks, weekly in month 2, every 2 weeks during months 3–6) |
| Measures | MADRS, Y-BOCS |
| Topics | Depression Esketamine |
| Key findings | During six months of routine-care intranasal esketamine for treatment-resistant depression, the patient's obsessive-compulsive symptoms improved alongside her depression, with MADRS scores falling from 38 to 17 and Y-BOCS scores from 33 to 14. The authors state 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. |
Abstract
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.
In the evidence
This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.
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Over six months of intranasal esketamine, MADRS fell from 38 to 17 and Y-BOCS from 33 to 14, though the authors state the observation cannot distinguish a direct anti-obsessional effect from nonspecific factors.
Synthesized
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Six months of intranasal esketamine was accompanied by reductions in depression (MADRS 38 to 17) and obsessive-compulsive symptoms (Y-BOCS 33 to 14), though the authors state the observation is hypothesis-generating.
Synthesized
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State of the evidence: Ketamine Supports
During six months of intranasal esketamine, obsessive-compulsive symptoms improved alongside depression (MADRS 38 to 17, Y-BOCS 33 to 14), though the authors state the observation cannot distinguish a direct anti-obsessional effect from nonspecific factors.
Synthesized
Comparable studies
Other case reports and case series on esketamine for depression, most cited first.