Ultra-low-dose ketamine can curb opioid withdrawal

Many people who use fentanyl become trapped in their addiction out of fear and a low tolerance for the withdrawal symptoms, which include muscle cramps, nausea, chills, sweats and intense cravings.

They can't stop using fentanyl, and they also have trouble starting either of the two medications, methadone and buprenorphine, that can dramatically reduce their risk of overdose death.

Research findings published Aug. 29 in Addiction Science & Clinical Practice may offer hope. A pilot study showed that a small amount of ketamine can reduce or eliminate the withdrawal symptoms associated with quitting fentanyl.

"The main takeaway is that we have found an easier way for people trapped in the grip of fentanyl addiction to get started in treatment," said Dr. Lucinda Grande, a clinical assistant professor of family medicine at the University of Washington School of Medicine. She was the study's lead author.

"Methadone can be difficult to access due to strict federal regulations, and starting buprenorphine can cause severe withdrawal symptoms before those who start it become stabilized," added study co-author Dr. Tom Hutch. He is the medical director of the opioid treatment program at We Care Daily Clinics in Auburn, Wash. "Ketamine, at an imperceptibly low dose, helps bridge that gap."

Over 14 months, Grande and colleagues in Auburn and Olympia prescribed ketamine to 37 fentanyl-addicted patients whose fear of withdrawal symptoms had deterred them from trying buprenorphine. Twenty-four patients actually tried the drug, and 16 completed the transition to buprenorphine.

Most patients reported a reduction or elimination of withdrawal symptoms after each ketamine dose, the effect of which lasted for hours. Of the last 12 who completed the transition, 92% remained in treatment for at least 30 days.

Patients placed a ketamine lozenge or syrup under the tongue. The 16 mg dose is a small fraction of that typically used for anesthesia, the main clinical role of ketamine for 50 years, according to Grande. That dosage also is less than half of the smallest ketamine dose prescribed for depression treatment, an increasingly common use of this medication.

Researchers monitored patients daily or almost daily, and refined the treatment strategy based on patient response and prescriber experience.

Grande developed the concept after she learned that emergency-medicine physician and coauthor Dr. Andrew Herring of Oakland, California, used a higher, sedating dose of ketamine successfully in his emergency department to resolve a patient's severe case of withdrawal from fentanyl addiction.

Grande is a primary-care and addiction doctor in practice near Olympia who, in the past dozen years, has used low-dose ketamine to treat more than 600 patients for chronic pain and depression.

Ketamine has gained prominence in the news since actor Matthew Perry of the sitcom "Friends" overdosed on the drug and drowned. Perry had undergone high-dose ketamine treatment for depression, news reports have suggested.

"Our study underscores the enormous potential of this medication for addressing important health problems such as depression, chronic pain and now fentanyl-use disorder," said Grande. Ketamine's positive attributes have been overshadowed by Perry's death, she said.

Grande hopes this pilot study's results will be confirmed by larger studies. "I am excited about these results," she said. "This is a wonderful opportunity to save lives."