Dr. Michael Verbora the medical director of Field Trip, holds a blister pack of Ketamine lozenges at … [+]
A phase 2 clinical trial of 231 patients with treatment-resistant depression found that the oral use of an extended-release tablet of ketamine could help prevent another depressive episode and is more effective and safer than the intravenous application of the medication. Patients reported side effects like headaches, dizziness, and anxiety.
While ketamine is more commonly used as an anesthetic medication, in the last twenty years, researchers have demonstrated its antidepressant properties, especially for patients who do not benefit from conventional anti-depressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). In most published studies, researchers administered ketamine to patients intravenously but because the medication gets absorbed a lot more rapidly in the bloodstream, it could cause severe side-effects like hypertension, dissociation, and a fast heart rate.
“We hypothesized that an extended-release tablet formulation of ketamine could be an effective and well-tolerated treatment option for patients with treatment-resistant depression,” wrote lead researcher Paul Glue, a professor of psychological medicine at the University of Otago, New Zealand, and colleagues, in their study that was published in Nature Medicine on June 24, 2024.
During the first phase of the clinical trial, Glue and team administered 120 mg of their new ketamine formulation to 231 study participants for five days. While 165 patients were using antidepressants, the other 60 were not on antidepressants.
In the second phase, 168 participants were divided into two groups. One group received placebo pills and the other was administered 180 mg of ketamine tablets twice per week.
The team observed that while 71% of the patients in the placebo group experienced a relapse of a depressive episode, in the group of patients who took 180 mg of ketamine tablets as prescribed, only 43% of patients reported a relapse.
The most common side effects were dizziness, headache, dissociation, feeling abnormal, fatigue, and nausea. Around 11.6% of the patients who used oral ketamine tablets experienced dissociation, a mental process where a person feels disconnected or cut off from their sense of identity and thoughts, feelings, or memory. The good news was that none of the patients experienced any cardiovascular side effects like increased blood pressure.
“A common concern about most currently available ketamine and esketamine formulations is the risk of abuse. The extended-release ketamine tablets used in this study are exceptionally hard and difficult to shatter, due to annealing of polyethylene oxide during their manufacturing process,” the researchers explained.
“This property may make this formulation less likely to be diverted for abuse, due to difficulty in manipulation of the tablets. We were not aware of any participants reporting craving for the tablets, and only one participant was removed from the study for lack of compliance,” they added. “These attributes potentially improve the scalability of ketamine use in the community, due to reduced need for in-clinic monitoring, and would also reduce costs associated with clinic visits.”
However, the researchers highlighted that a limitation of their clinical trial’s results is that there is still relatively scant data on the efficacy and tolerability of using oral ketamine tablets compared to intravenous or intranasal dosing, and that “it is not possible to directly compare the present study’s findings with studies using non-oral routes of administration.”