A new pill that releases ketamine slowly over time could treat severe depression without causing the psychedelic side effects often associated with the drug.
Early trial results, published in Nature Medicine, suggest this pill might offer a safer alternative for those who don’t benefit from common antidepressant medications.
Ketamine, first developed in the 1960s as an anesthetic, is known for its hallucinogenic effects, which have led to its misuse as a party drug known as “Special K.”
Despite its reputation, research has shown ketamine’s effectiveness in treating approximately a quarter of people with depression who see little benefit from traditional antidepressants.
In several countries, ketamine has been prescribed for depression for years, with notable figures like Elon Musk publicly endorsing its benefits.
Traditionally administered intravenously in clinics, ketamine treatment has recently evolved to include a nasal spray derivative called esketamine.
Both methods can cause side effects like dissociation, high blood pressure, and elevated heart rate. Additionally, there are concerns about the potential for abuse.
The new pill, studied by lead author Paul Glue from New Zealand’s University of Otago, takes more than 10 hours to break down in the liver. This extended release appears to mitigate the common side effects associated with ketamine.
“The feedback from patients indicates a lack of side effects—no euphoria, no dissociation,” said Glue. “These tablets likely wouldn’t appeal to those who abuse ketamine.”
Promising Trial Results
In a phase 2 trial involving over 270 people with depression who had previously tried an average of four different antidepressant drugs, more than half of those taking the ketamine pill went into remission.
In contrast, 70 percent of the placebo group relapsed after 13 weeks. Julaine Allan, a mental health and addiction expert from Australia’s Charles Sturt University, praised the trial while noting the need for further research.
She emphasized that while ketamine can be effective, its positive effects may diminish over time.
Michel Hofmann, a psychiatrist at Geneva University Hospitals, expressed enthusiasm for ketamine’s potential, especially as an alternative to electro-shock therapy for patients unresponsive to conventional treatments.
Electro-shock therapy, though effective, can cause memory loss and is often feared by patients due to negative portrayals in media.
Addressing Concerns and Looking Forward
Some psychiatrists remain cautious about prescribing ketamine due to the risk of misuse. Last year, “Friends” actor Matthew Perry’s death from a ketamine overdose highlighted these concerns.
Researchers hope that the slow-release pill, by eliminating the sought-after side effects of recreational ketamine use, could mitigate these risks. However, the pill is not entirely free of side effects, with some patients reporting headaches, dizziness, and anxiety.
More research, including phase 3 trials, is necessary before the slow-release ketamine pill can be reviewed by national medicine agencies.
If approved, it could become available to patients within two to three years, offering a new hope for those struggling with severe depression.
If you care about depression, please read studies about how dairy foods may influence depression risk, and B vitamins could help prevent depression and anxiety.
For more information about mental health, please see recent studies that ultra-processed foods may make you feel depressed, and extra-virgin olive oil could reduce depression symptoms.
The research findings can be found in Nature Medicine.
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