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Slow-release ketamine pills have demonstrated effectiveness in preventing relapse into depression, marking a potential breakthrough in treatment for severe mental illness.

Ketamine, already utilized when traditional antidepressants and therapy prove ineffective, is presently administered intravenously under clinic supervision. The National Institute for Health and Care Excellence has withheld approval for a ketamine-like nasal spray on the NHS.

Should ongoing trials validate these initial benefits, researchers anticipate that ketamine tablets could offer a more accessible, cost-effective, and potentially safer option for patients.

"We're seeing a clinically meaningful effect," said Prof. Allan Young, co-author of the findings from King's College London. "This is not a definitive result, but the effect size is gratifyingly large."

The phase 2 trial employed an extended-release ketamine formulation designed to deliver the drug over a 10-hour period. This approach aims to enhance treatment efficacy while minimizing adverse effects such as dissociation, elevated blood pressure, rapid heart rate, or numbness-a "slow peak" strategy intended to reduce abuse potential, explained Young.

Many depression treatments fail to benefit a significant subset of patients. Addressing this challenge, the trial adopted an innovative methodology: initially administering the new formulation to 231 participants for five days to identify "treatment responders." Of these, 168 showing substantial symptom reduction proceeded to the trial's second phase, where they were randomly assigned to receive either ketamine tablets or a placebo.

Results revealed that 43% of patients receiving ketamine tablets twice weekly experienced depression relapse after 13 weeks, compared to 71% in the placebo group, The Guardian reported.

Side effects among patients were minimal, with no significant changes in blood pressure reported; however, higher doses correlated with increased incidences of dissociation and dizziness. Tragically, a 65-year-old participant in the treatment group died by suicide, attributed by investigators to underlying illness rather than treatment effects.

Researchers envision ketamine becoming an alternative for millions suffering from chronic depression unresponsive to conventional drugs like selective serotonin reuptake inhibitors (SSRIs), which act primarily on serotonin. Ketamine, in contrast, affects glutamate, another neurotransmitter.

Dr. Rupert McShane of Oxford Health NHS trust hailed the findings as encouraging, envisioning a safer, long-term alternative akin to intravenous ketamine benefits.

Despite optimism, the suitability of ketamine treatments for broader depression populations remains uncertain pending further trials, cautioned Dr. Paul Keedwell, emphasizing the need for continued research into optimal dosing and individual variability in absorption.

The study, published in Nature Medicine, marks a significant stride towards expanding treatment options for severe depression.