A recent open-label clinical trial conducted at the University of the Sunshine Coast (UniSC) in Australia indicates that low doses of oral ketamine can significantly alleviate symptoms of post-traumatic stress disorder (PTSD). The study, conducted at the National PTSD Research Centre at UniSC, explored the feasibility, safety, and tolerability of oral ketamine as a treatment option, potentially offering a more accessible alternative to intravenous (IV) administration.
The research involved 22 participants aged 22-77 years, including individuals with lifelong PTSD and comorbid depression. Participants received weekly doses of oral ketamine for six weeks. The results, published in European Neuropsychopharmacology, revealed that 73% of participants experienced a reduction of more than 50% in their PTSD symptoms one week post-treatment. Moreover, 59% maintained this improvement one month after the final dose.
Oral vs. Intravenous Ketamine
Ketamine, a short-acting anesthetic, is being investigated for its rapid antidepressant and anti-PTSD effects. Traditionally, ketamine is administered via injections or infusions in a clinical setting. Senior investigator Professor Dan Hermens noted that the oral administration of ketamine could address existing gaps in understanding optimal dosage and delivery methods. "Despite extensive studies on IV ketamine infusions, there are gaps in understanding the most effective dosage levels and the best way to administer the drug as a treatment," Professor Hermens stated.
Lead author Dr. Bonnie Quigley highlighted the advantages of oral ketamine over IV ketamine. "Oral ketamine patients can be treated at their doctor's office – while IV ketamine needs to be administered in a hospital or clinic setting under medical supervision," Dr. Quigley explained. "This limits its use, especially for treatment programs that require daily or intermittent dosing schedules."
Improved Mental Health Outcomes
Beyond PTSD symptom reduction, participants reported improvements in several mental health domains. These included decreased depression, stress, and suicidal ideation, along with enhanced sleep quality, social and occupational functioning, and overall wellbeing. Professor Hermens emphasized the significance of these broad improvements, noting that "over 90 percent of people diagnosed with PTSD also experience a psychiatric disorder such as suicidal ideation, anxiety, alcohol use disorders and depression."
Safety and Tolerability
The study also highlighted the safety and tolerability of oral ketamine. Participants reported fewer side effects compared to IV ketamine, such as headaches, dizziness, breathing difficulties, irregular heartbeat, and feelings of dissociation. "Importantly, all participants reported that side effects from oral ketamine had resolved before their discharge from the study," Dr. Quigley added. The gradual increase in ketamine dosage throughout the trial was designed to optimize tolerability while maximizing therapeutic benefits.
Future Directions
The researchers believe these findings warrant further investigation into oral ketamine as a viable treatment strategy for PTSD. The UniSC's National PTSD Research Centre is continuing research in this area, including studies on Reconsolidation Therapy, a non-invasive approach to reduce the emotional impact of traumatic memories.
