Slow-release ketamine tablets help prevent relapses of depression, according to a British study
Slow-release ketamine pills appear to prevent relapse into depression, in a study that could pave the way for a new treatment option for patients with serious illness.
Ketamine is already used as a treatment for depression when conventional antidepressants and therapy have failed. But ketamine is currently only administered intravenously, which requires supervision in a clinic, and the National Institute for Health and Care Excellence has ruled that a ketamine-like nasal spray should not be available on the NHS.
If the apparent benefits are confirmed in a larger trial, ketamine tablets could be cheaper, easier and possibly with fewer side effects to take at home, the researchers said.
“We see a clinically meaningful effect,” says Prof. Allan Young of King’s College London and co-author of the findings. “This is not a definitive result, but the effect size is gratifyingly large.”
The Phase 2 study used an extended-release formulation of ketamine, designed to release the drug into the body over a 10-hour period. The hope was that this would make the treatment more effective and reduce side effects such as dissociation, high blood pressure, palpitations or numbness. The “slow peak” would also reduce the drug’s abuse potential, Young said.
A significant proportion of patients do not respond to most depression treatments – including those that have proven effective. To get around this challenge, the latest study used an innovative design in which all 231 were initially given the new drug formulation for five days to identify ‘treatment responders’. Of these, the 168 who showed a significant reduction in symptoms entered the second phase of the study, where they were randomly assigned to continue taking ketamine tablets or to receive a placebo.
In the placebo group, 71% of patients experienced a relapse in depression after 13 weeks, compared with 43% of patients who received the tablets twice a week. The patients had no significant changes in blood pressure and minimal reports of drowsiness. However, those who received higher doses and who seemed to benefit most were also more likely to report feelings of dissociation and dizziness. There was also the suicide of a 65-year-old man in the treatment group, which the lead researcher believed was due to his illness rather than the treatment.
The team behind the trial hopes the drug can become an alternative for the millions of people with chronic depression who have not responded to conventional medications. The most commonly used medications, known as selective serotonin reuptake inhibitors (SSRIs), are thought to act on the brain chemical serotonin, while ketamine appears to act on another neurotransmitter called glutamate.
Dr. Rupert McShane, consultant psychiatrist at Oxford Health NHS Trust, said the findings were encouraging. “If a form of ketamine can be found that mimics the benefit of intravenous ketamine and is safe in the long term, that would be a huge advance,” he said.
However, he added that it was not yet clear whether ketamine treatments alone would remain an appropriate treatment for severe cases of depression, or whether trial evidence would eventually support more mainstream applications. “Whether it has a place in the wider population is uncertain and this is a good way to test this,” he said.
Dr. Paul Keedwell, a consultant psychiatrist, said: “This new study further underlines the impressive antidepressant effect of ketamine, but in the much more convenient and acceptable form of a slow-release tablet. A potential disadvantage of oral ketamine is that there are likely large individual differences in absorption and metabolism, so further research is needed to determine the ideal dosing regimen.”
The findings were published in Naturopathy.