Six weeks open-label oral ketamine for patients with treatment-resistant depression, post-traumatic stress disorder, or obsessive-compulsive disorder.

In an open-label extension of a prior crossover trial, oral ketamine was given for six weeks to people with treatment-resistant depression, post-traumatic stress disorder, or obsessive-compulsive disorder. Doses started at 1-1.5 mg/kg and increased to 1.5-2.5 mg/kg, taken one to three times per week. Symptom scores remained low throughout the six weeks, and the oral formulation was well tolerated with few side effects. The findings suggest that oral ketamine can sustain improvements in these treatment-resistant conditions and offers a practical alternative for maintenance therapy.

Study at a glance

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.