Intranasal racemic ketamine in treatment-resistant depression: Efficacy and tolerability in outpatient treatment

Background and aim: Intranasal racemic ketamine is an off-label alternative for treatment-resistant depression (TRD), offering a non-invasive and compared to esketamine less expensive option. However, its efficacy and safety in outpatient settings remain underexplored. This study aimed to assess the...

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Main Authors: Jan Sarlon, Timur Liwinski, Annette Beatrix Bruehl, Deanne Thomi, Undine Emmi Lang
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Journal of Affective Disorders Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666915325000848
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author Jan Sarlon
Timur Liwinski
Annette Beatrix Bruehl
Deanne Thomi
Undine Emmi Lang
author_facet Jan Sarlon
Timur Liwinski
Annette Beatrix Bruehl
Deanne Thomi
Undine Emmi Lang
author_sort Jan Sarlon
collection DOAJ
description Background and aim: Intranasal racemic ketamine is an off-label alternative for treatment-resistant depression (TRD), offering a non-invasive and compared to esketamine less expensive option. However, its efficacy and safety in outpatient settings remain underexplored. This study aimed to assess the safety, tolerability, and efficacy of intranasal racemic ketamine in patients with TRD. Methods: This retrospective analysis included 45 patients (mean age 50.7 years, 21 women) who completed an induction phase of eight treatments with intranasal racemic ketamine over four weeks. Symptom severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). A complete response was defined as a ≥ 50 % reduction in MADRS scores from baseline, and a partial response as a 25–50 % reduction. Results: The mean racemic ketamine dose was 114.0 mg, the mean MADRS score reduction after four weeks was 34.5 %. The mean increase in blood pressure was 7.4 mmHg systolic and 6.9 mmHg diastolic. A paired t-test comparing baseline and week 8 MADRS scores revealed a statistically significant reduction in scores, with a mean difference of 10.04. Cohen’s d for MADRS reduction was 1.30, indicating a large effect. A total of 31.1 % of patients achieved a complete response, and 33.3 % had a partial response. Euphoria was a significant predictor of treatment response (p < 0.001). Adverse events requiring medical intervention occurred in four patients, and the drop-out rate due to adverse effects was 4.2 %. Conclusions: Intranasal racemic ketamine is an effective, well-tolerated treatment for TRD, with favorable safety outcomes and substantial antidepressant effects.
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spelling doaj-art-ebe89851310d4004adc6e25026bdcb6a2025-08-20T03:55:53ZengElsevierJournal of Affective Disorders Reports2666-91532025-07-012110095410.1016/j.jadr.2025.100954Intranasal racemic ketamine in treatment-resistant depression: Efficacy and tolerability in outpatient treatmentJan Sarlon0Timur Liwinski1Annette Beatrix Bruehl2Deanne Thomi3Undine Emmi Lang4University Psychiatric Clinics (UPK) Basel, Switzerland; University of Basel, Switzerland; Corresponding author at: Centre of Affective, Stress- and Sleep Disorders (ZASS), University Psychiatric Clinics (UPK) Basel, Switzerland.University Psychiatric Clinics (UPK) Basel, Switzerland; University of Basel, SwitzerlandUniversity Psychiatric Clinics (UPK) Basel, Switzerland; University of Basel, SwitzerlandUniversity Psychiatric Clinics (UPK) Basel, Switzerland; University of Basel, SwitzerlandUniversity Psychiatric Clinics (UPK) Basel, Switzerland; University of Basel, SwitzerlandBackground and aim: Intranasal racemic ketamine is an off-label alternative for treatment-resistant depression (TRD), offering a non-invasive and compared to esketamine less expensive option. However, its efficacy and safety in outpatient settings remain underexplored. This study aimed to assess the safety, tolerability, and efficacy of intranasal racemic ketamine in patients with TRD. Methods: This retrospective analysis included 45 patients (mean age 50.7 years, 21 women) who completed an induction phase of eight treatments with intranasal racemic ketamine over four weeks. Symptom severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). A complete response was defined as a ≥ 50 % reduction in MADRS scores from baseline, and a partial response as a 25–50 % reduction. Results: The mean racemic ketamine dose was 114.0 mg, the mean MADRS score reduction after four weeks was 34.5 %. The mean increase in blood pressure was 7.4 mmHg systolic and 6.9 mmHg diastolic. A paired t-test comparing baseline and week 8 MADRS scores revealed a statistically significant reduction in scores, with a mean difference of 10.04. Cohen’s d for MADRS reduction was 1.30, indicating a large effect. A total of 31.1 % of patients achieved a complete response, and 33.3 % had a partial response. Euphoria was a significant predictor of treatment response (p < 0.001). Adverse events requiring medical intervention occurred in four patients, and the drop-out rate due to adverse effects was 4.2 %. Conclusions: Intranasal racemic ketamine is an effective, well-tolerated treatment for TRD, with favorable safety outcomes and substantial antidepressant effects.http://www.sciencedirect.com/science/article/pii/S2666915325000848DepressionNasal racemic ketamineResponseTolerabilityCost-effectiveness
spellingShingle Jan Sarlon
Timur Liwinski
Annette Beatrix Bruehl
Deanne Thomi
Undine Emmi Lang
Intranasal racemic ketamine in treatment-resistant depression: Efficacy and tolerability in outpatient treatment
Journal of Affective Disorders Reports
Depression
Nasal racemic ketamine
Response
Tolerability
Cost-effectiveness
title Intranasal racemic ketamine in treatment-resistant depression: Efficacy and tolerability in outpatient treatment
title_full Intranasal racemic ketamine in treatment-resistant depression: Efficacy and tolerability in outpatient treatment
title_fullStr Intranasal racemic ketamine in treatment-resistant depression: Efficacy and tolerability in outpatient treatment
title_full_unstemmed Intranasal racemic ketamine in treatment-resistant depression: Efficacy and tolerability in outpatient treatment
title_short Intranasal racemic ketamine in treatment-resistant depression: Efficacy and tolerability in outpatient treatment
title_sort intranasal racemic ketamine in treatment resistant depression efficacy and tolerability in outpatient treatment
topic Depression
Nasal racemic ketamine
Response
Tolerability
Cost-effectiveness
url http://www.sciencedirect.com/science/article/pii/S2666915325000848
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