Researchers have marked 10 years since the world’s first clinical program saw a common horse tranquilizer given to people suffering from depression, in what was to become one of the biggest psychiatric breakthroughs in 50 years.
When psychiatrist David Feifel established the first program using ketamine to treat patients with depression, many considered it a hare-brained idea.
It was in the waning months of 2008 that he launched the programme, giving intravenous ketamine to patients with depression.
Ketamine, approved as a human anesthetic in 1969, is perhaps best known as a horse tranquilizer and a recreational club drug.
It was by no means an obvious choice as a breakthrough treatment for depression.
Feifel, a tenured professor of psychiatry at the University of California, San Diego, at the time, nevertheless saw ketamine’s potential after reading a 2006 paper by a team of researchers at the National Institutes of Health in the US, who observed rapid antidepressant effects in a small group of patients suffering from chronic depression after they received a low dose of the drug intravenously.
“I was skeptical about those results,” he admits, “but I figured if ketamine worked half as good as described in that paper, then it would be a game changer since millions of people live with debilitating depression that is not alleviated by conventional treatments and many of them end their life.”
It took Feifel many months to get the health system at his university to approve his request to give ketamine to severely depressed patients, but once they did his skepticism gave way to awe and excitement.
Patients were emailing, saying things like, “Today was the first beautiful day of my life” and “I finally know what it’s like to be glad to be alive.”
While patients heaped gratitude on him, the reaction among many of his colleagues in the psychiatry establishment was far less supportive.
“Many thought it was too risky to be giving it to patients until much more research was conducted, but with over 40,000 suicides a year in the US, I felt the risk of not offering this potentially life-saving drug to severely depressed patients outweighed the risks of offering it.”
In 2017, Feifel and several colleagues published an analysis of antidepressant resistant patients that he had treated with intravenous ketamine.
They found that, on average, there was a 50% reduction in the severity of depression symptoms 24 hours after the first ketamine treatment and 40% of the patients no longer met the threshold for clinical depression.
It was the first confirmation that ketamine worked in patients who were receiving it in an authentic treatment context as well as it did in well-controlled clinical trials in which patients were carefully selected.
Considered audacious for treating depressed patients with ketamine in 2008, Feifel, now a professor emeritus at the university and the director of Kadima Neuropsychiatry Institute, an independent treatment and research facility, has since been joined by dozens of physicians across the US and abroad who routinely use ketamine to treat depressed patients who have failed other approaches.
The drug has also become increasingly recognized as a major breakthrough treatment by mainstream psychiatry.
The American Psychiatric Association recently issued guidelines for using the treatment and Cleveland Clinic recently listed ketamine for depression in its top 10 list of medical breakthroughs.
In September, Johnson and Johnson submitted a new drug application to the FDA to market a modified ketamine drug that can be taken via the nose, and several other pharmaceutical companies are developing drugs for depression based on ketamine.
As for Feifel, having administered thousands of ketamine treatments, he and his team continue to push the envelope developing new ways to optimize its therapeutic effects, which are now recognized to include benefits for those with post-traumatic stress disorder, obsessive compulsive disorder, and even drug and alcohol addiction.
To mark the start of his second decade of using ketamine to treat psychiatric conditions, Feifel and his team plan to roll out two new innovations that they believe will help with the effects of ketamine and are investigating several others.
“I have not seen any treatment in my career as dramatically effective as ketamine,” he says, “but it’s far from perfect and there is much work yet to be done.”
Feifel D, Malcolm B, Boggie D, Lee K. Low-Dose Ketamine for Treatment Refractory Depression in an Academic Clinical Practice Setting, Journal of Affective Disorders, 2017, 221:283–288
Feifel, D. Breaking Sad: Unlocking the Breakthrough Potential of Ketamine’s Rapid Antidepressant Effects. Drug Development Research. 2016, 77(8):489-494.