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Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series.

Maryam I Al Shirawi, Sidney H. Kennedy, Keith T. Ho, Roisin Byrne, Jonathan Downar

Journal of Clinical Psychopharmacology August 2017 DOI: 10.1097/jcp.0000000000000717 (opens in new tab)

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Characteristics Retrospective case series Open-label Case report Peer reviewed
Sample size 22
Population Adults with treatment-resistant depression who had failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation
Intervention Oral ketamine
Dose commenced at 50 mg every 3 days, titrated up by 25 mg every 3 days
Measures Beck Depression Inventory II
Topics Depression Esketamine Ketamine
Key findings Oral ketamine produced greater than 50% reduction in Beck Depression Inventory II scores in 18% of patients and partial improvement in 14%, while 45% had no response and 23% had mild worsening of depressive symptoms. The authors report that oral ketamine was safe and well tolerated, with no serious adverse effects, abuse, or dependence, but conclude that effectiveness was modest and that further exploration is warranted given the limitations of this small, open-label case series.

Abstract

The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression. We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained. Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed. Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.

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
Oral Administration of the NMDA Receptor Antagonist S-Ketamine as Add-On Therapy of Depression: A Case Series Four depressed patients taking standard antidepressants 2009 Case series n = 4
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

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