Ketamine is being actively investigated as a rapid-acting treatment for many conditions with a stress-related psychopathology, including post-traumatic stress disorder (PTSD). The majority of studies regarding ketamine treatment for PTSD to date (including open-label and randomised control trials) have focused on intravenous (IV) ketamine administration. This administration route has limitations that can be overcome with oral ketamine. As such, this study undertook the first open-label low dose Oral Ketamine Trial on PTSD (OKTOP) to determine the safety and feasibility of sub-anaesthetic ketamine for PTSD symptom reduction. Participants with PTSD (n = 22 adults, aged 22-77 years, 55% female, 82% with comorbid depression) followed a weekly treatment course of low dose oral ketamine (titrated from 0.5 mg/kg to a maximum of 3.0 mg/kg) for six weeks. The primary outcome measure was the PTSD Checklist (PCL-5), with secondary measures including scales for depression, anxiety, stress, suicidality, sleep, and wellbeing. Mean PCL-5 scores were significantly reduced from a pre-ketamine baseline score of 40 to a post-ketamine score of 17 and remained at a reduced score (21) at follow-up, 1-month post-treatment. This reduction resulted in a response rate (defined as a ≥50% reduction in PCL-5 score from baseline) of 73% post-ketamine and 59% at follow-up. This response rate is comparable with IV ketamine trials for PTSD and suggests oral ketamine administration is a feasible and tolerable treatment for PTSD.

The authors have declared no competing interest.

Clinical Trials Registry of Australia and New Zealand (ACTRN12618001965291)

The funding for this project was provided by the internal budget of the Thompson Institute, University of the Sunshine Coast, Australia.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Metro North Health Human Research Ethics Committee (HREC) granted ethical approval for this study (Project ID: 42836; HREC/18/QPCH/28), and the University of the Sunshine Coast HREC subsequently confirmed that ethical approval (A181190)

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Yes

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All data produced in the present study are available upon reasonable request to the authors