Six weeks open-label oral ketamine for patients with treatment-resistant depression, post-traumatic stress disorder, or obsessive-compulsive disorder.
Ben Beaglehole, Paul Glue, Shona Neehoff, Shabah M. Shadli, Neil McNaughton, Bridget Kimber, Chrissie Muirhead, Aroha de Bie, Rachel Day-Brown, Natalie J Hughes-Medlicott
Journal of Psychopharmacology June 5, 2025 DOI: 10.1177/02698811251344710 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label extension study Randomized Double-blind Peer reviewed |
|---|---|
| Sample size | 43 |
| Population | Participants with treatment-resistant depression (TR-D), post-traumatic stress disorder (TR-PTSD), or obsessive-compulsive disorder (TR-OCD) |
| Intervention | Oral ketamine |
| Dose | 1-1.5 mg/kg increasing to 1.5-2.5 mg/kg, 1-3 times per week |
| Duration | 6-week course |
| Topics | Depression Ketamine PTSD Esketamine |
| Keywords | Psychopharmacology Ketamine therapy OCD Trd Maintenance treatment Oral Mental health treatment Treatment-resistant conditions Psychiatric medicine |
| Citations | 19 |
| Key points | Oral ketamine sustained low symptom scores over six weeks in treatment-resistant depression, PTSD, and OCD, and was well tolerated. |
Abstract
We previously completed a double-blind randomised crossover study assessing intramuscular ketamine for treatment-resistant depression (TR-D), post-traumatic stress disorder (TR-PTSD) and obsessive-compulsive disorder (TR-OCD). Here, we report an extension study to explore the ongoing benefits and tolerability of maintenance oral ketamine. All participants from the original study were eligible to receive a 6-week open-label course of oral ketamine once-thrice weekly. Racemic ketamine for injection was diluted in orange juice and sipped over 30-60 min. Dose amount and frequency were adjusted individually to maximise benefits and tolerability. Effectiveness was assessed by disorder-specific scales. Side effects and tolerability were assessed using reported adverse events and scales for dissociation and urinary/bladder symptoms. Seventeen participants with TR-D, 18 participants with TR-PTSD and 8 participants with TR-OCD commenced oral ketamine. Nine participants with TR-D, 16 participants with TR-PTSD and 5 participants with TR-OCD completed all 6 weeks of dosing. Ketamine dose increased over time from 1-1.5 mg/kg to 1.5-2.5 mg/kg, with a dosing frequency of 1-3 times/week, with an average total dose rising from 1.9 to 3.0 mg/kg/week over the first 3 weeks. Symptom rating scores for TR-D, TR-PTSD and TR-OCD were low at week 1 of oral dosing (compared to scores at entry into the original study) and remained low throughout the six-week course of oral ketamine. Oral ketamine was well tolerated with minimal side effects. The 6-week extension of oral ketamine appeared to sustain improvements for TR-D, TR-PTSD and TR-OCD. Oral ketamine was well tolerated and offers an alternative option for patients, researchers and clinicians.
Comparable studies
Other non-randomized and open-label trials on ketamine for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Efficacy and Safety of Intranasal Esketamine in Patients With Treatment-Resistant Depression and Comorbid Chronic Post-traumatic Stress Disorder: Open-Label Single-Arm Pilot Study Patients with treatment-resistant major depressive disorder and comorbid post-traumatic... | 2022 | Open-label, single-arm, retrospective pilot study | n = 11 |
| Ketamine for treatment-resistant post-traumatic stress disorder: double-blind active-controlled randomised crossover study Community sample of individuals with PTSD | 2025 | Clinical trial | |
| Clinical indicators of the suicide crisis and response to ketamine. Adults across the continuum of suicide risk, including 14 high-risk individuals who had... | 2025 | Observational cohort with open-label intervention | n = 118 |
| Ketamine-assisted psychotherapy provides lasting and effective results in the treatment of depression, anxiety and post traumatic stress disorder at 3 and 6 months: Findings from a large single-arm retrospective effectiveness trial Adults with a history of depression, anxiety, or PTSD who had not responded to prior... | 2023 | Retrospective single-arm effectiveness trial | n = 1,806 |
| Brain State Dynamics in Ketamine-Induced Dissociation Resemble Those in Posttraumatic Stress Disorder. Healthy volunteers and patients with PTSD | 2026 | Observational cohort with experimental manipulation and secondary analysis of clinical trial data | n = 108 |
Citations in the library
Cited by 9
- Esketamine/Ketamine: Dual‐Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology Advanced Science December 14, 2025
- Intranasal Esketamine Augmentation in Treatment-Resistant Obsessive–Compulsive Disorder with Comorbid Treatment-Resistant Depression: A Six-Month Case Report Psychiatry International September 10, 2026
- Ketamine for the Treatment of Obsessive-Compulsive Disorder (OCD): A Systematic Review on Efficacy and Tolerability. Clinical Neuropharmacology June 19, 2026
- Ketamine and Esketamine in Obsessive-Compulsive Disorder: A Scoping Review of Clinical and Mechanistic Evidence. Pharmaceuticals April 16, 2026
- Hope for Neurotic Disorders: A Summary of New Zealand Research on the Development of Biomarkers and Novel Treatments. Journal of the Royal Society of New Zealand February 1, 2026
and 4 more in the library
Cites 14
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Blinding and expectancy confounds in psychedelic randomized controlled trials Expert Review of Clinical Pharmacology May 26, 2021
and 9 more in the library