pictureSince fentanyl has dominated the illicit drug supply in the United States, doctors and patients have found it increasingly difficult to use buprenorphine, a leading addiction drug.
In many cases, fentanyl’s potency has meant that patients transitioning to the much weaker drug buprenorphine experience excruciating symptoms known as “sudden withdrawal.” patients give up buprenorphine altogether.
But three West Coast doctors are reporting breakthroughs in buprenorphine thanks to an unlikely drug. Ketamine is an anesthetic that has both medicinal and recreational use and has hallucinogenic effects at high doses. When patients were given a small dose of ketamine when starting buprenorphine treatment, withdrawal symptoms nearly disappeared, they say.
“People come in traumatized by sudden withdrawal symptoms,” says Cindy Grande, a Washington state addiction specialist who has helped dozens of patients transition to buprenorphine using ketamine. I was very wary of using buprenorphine. For those patients, the addition of ketamine was “like a miracle,” she said.
The discovery of ketamine as a potential addiction treatment adjunct highlights the current crisis. Currently, only two drugs are approved for treatment of withdrawal symptoms and opioid cravings: methadone and buprenorphine. And with more than 80,000 Americans dying each year from opioid overdoses, the need for medical treatment has never been greater.
However, methadone is only available in specialized clinics. Also, buprenorphine, often referred to by the generic brand name Suboxone, can be prescribed by any doctor, but is increasingly associated with painful withdrawal symptoms. Sometimes the discomfort is so severe that patients give up buprenorphine altogether and resume illicit drug use despite their desire to quit.
“The standard approach to buprenorphine in the fentanyl era can make patients feel like they’re throwing penicillin at a superbug,” says teaming up with Grande to provide ketamine for patients starting addiction treatment. Said Thomas Hutch, a Seattle-area addiction doctor who is working with ketamine. It’s your turn.”
The ketamine approach is just the latest example of doctors getting creative in the process of initiating buprenorphine treatment, also known as buprenorphine “induction.”
In response to fentanyl’s potency and seemingly rapid withdrawal, some doctors began administering much more buprenorphine than they had been a few years earlier. Buprenorphine is “microdosed” over several days to reduce discomfort while encouraging the patient to slowly reduce illicit drug use. It offered patients a bold and painful approach, using the drug naloxone to intentionally initiate withdrawal and then using large doses of buprenorphine to end it.
But ketamine proponents say it offers an easier means of initiating treatment. So far, the medical community has responded enthusiastically.
Grande, Hatch, and Andrew Herring, an addiction physician based in Oakland, California, received rave reviews after presenting their ketamine approach at the American Society of Addiction Medicine’s annual conference last month.
According to Hatch, the trio came together naturally. Herring, who is also an emergency physician, has experience using ketamine to help inpatients on buprenorphine induction. Grande had previously used ketamine to treat pain and depression. And Hatch, the medical director of the opioid treatment program, had many patients who would benefit from ketamine, and sent many of them to Grande.
Although promising, positive results with the combination of ketamine and buprenorphine have been limited to a small subset of populations. No randomized trials have been conducted and there is little existing medical literature on its practice. (His one of his 2021 papers, in which Herring is listed as a co-author, details his one case of a patient whose severe withdrawal symptoms were relieved with intravenous ketamine.)
Still, this approach looks very promising. Ketamine is not an experimental drug, and doctors are pretty much free to prescribe it to patients. She said it was between 1% and 2% of what she called a “typical anesthetic dose.”
But this strategy is so new that doctors are still divided on why it is so effective. and is a perfect treatment for withdrawal symptoms. However, Hatch is skeptical, arguing that the dosage is simply too low to be effective in reducing pain.
Hutch’s theory is based on the incredibly high opioid tolerance that fentanyl users often develop, as a result of which once standard buprenorphine doses feel inadequate. It magnifies the effect and makes doses that were once inadequate sufficient.
“You can think of it like a buprenorphine amplifier,” he said.
Physicians have yet to establish a consistent protocol for ketamine use. Ketamine may be used to treat withdrawal symptoms after the first dose of buprenorphine or as a prophylactic measure to prevent withdrawal symptoms altogether.
But in both scenarios, Grande said, the results were surprising.
“The first patient I treated with this had 18 hours of withdrawal,” she said. She took a quarter of that, 4 milligrams, and that was enough.She felt better within five minutes.”
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