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Intravenous ketamine for treatment-resistant depression patients who have failed to respond to transcranial magnetic stimulation: A case series.

Olivier Payette, Paul Lespérance, V. D. Jodoin, Christophe Longpré-poirier, Laurent Elkrief, Maxime Richard, Nicolas Garel, J. Miron

Journal of Affective Disorders April 1, 2023 DOI: 10.1016/j.jad.2023.04.019 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Case series Open-label Case report Peer reviewed
Sample size 21
Population Adults with treatment-resistant depression who had failed to respond to TMS
Intervention Ketamine
Dose 0.5 mg/kg over 60 min
Duration 2-week intervention period
Measures MADRS
Topics Depression Esketamine Ketamine
Citations 7
Key findings Intravenous racemic ketamine reduced depression severity in patients with treatment-resistant depression after TMS failure, with 19% responding and 9.5% achieving remission.

Abstract

Background: For individuals with treatment-resistant depression (TRD), transcranial magnetic stimulation (TMS) has become a well-established approach. In the past decade, intravenous (IV) racemic ketamine has also emerged as a potential treatment for TRD. Currently, little data is available on the clinical effects of IV racemic ketamine in TRD patients who experienced TMS-failure.

Methods: Twenty-one (21) TRD patients who had failed to respond to a standard course of high-frequency left-dorsolateral prefrontal cortex TMS were subsequently scheduled to received IV racemic ketamine infusions. The IV racemic ketamine protocol consisted of 0,5 mg/kg infusions over 60 min, 3 times a week over 2 weeks.

Results: Treatment was safe with minimal side-effects. Mean baseline MADRS score was 27.6 ± 6.4 (moderate depression), decreasing down to 18.6 ± 8.9 (mild depression) post-treatment. Mean percent improvement was 34.5 % ± 21.1 from baseline to post-treatment. Paired sample t-test showed significant MADRS score decrease pre- to post-treatment [t(20) = 7.212, p < .001]. Overall, four (4) patients (19.0 %) responded and two (2) of those achieved remission (9.5 %).

Limitations: Limitations of this case series include its retrospective and uncontrolled open-label nature, the lack of self-rating and standardized adverse events questionnaires, as well as follow-ups beyond the immediate treatment period.

Conclusions: Novel ways to increase the clinical effects of ketamine are being explored. We discuss potential combination approaches of ketamine with other modalities to augment its effects. Given the global burden of TRD, novel approaches are needed to curb the current mental health epidemic around the world.

Comparable studies

Other case reports and case series on ketamine for depression, most cited first.

Study Year Design Participants
Electroconvulsive Therapy, Ketamine, and Esketamine in a Patient with Major Depressive Disorder and Multiple Comorbidities: A Case Report over 10-year Treatment from Adolescence to Adulthood. A patient with treatment-resistant depression and comorbid generalized anxiety... 2025 Case report n = 1
A longitudinal case series of IM ketamine for patients with severe and enduring eating disorders and comorbid treatment‐resistant depression Patients with enduring eating disorders and treatment-resistant depression 2021 Case series n = 4
Effects of intranasal (S)-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series Veterans with co-morbid depression and PTSD 2022 Retrospective case series n = 35
Case report: Intramuscular ketamine or intranasal esketamine as a treatment in four patients with major depressive disorder and comorbid anorexia nervosa Patients with anorexia nervosa and a comorbid depressive disorder treated at a private... 2023 Case report n = 4
Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder Patients with treatment-resistant depression and comorbid PTSD 2023 Case series n = 5

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