Fentanyl use disorder is tricky to treat: 'Once they start to withdraw, they run'

• Fentanyl stays in opioid receptors in the brain longer than other opioids.
• If a patient is given one of the best medications for fentanyl use disorder, they can experience severe withdrawal.
• Withdrawal symptoms can chase patients back to use, interrupting recovery, risking their lives.

Doctors and other medical caregivers have been urged for years to get certified to prescribe a medication to patients with opioid use disorder to treat the addiction and reduce overdose deaths.

The medication is the U.S. Food and Drug Administration-approved buprenorphine, commonly known by a brand, Suboxone. Taken as prescribed, it's among the most effective ways to treat patients and protect them from overdose.

Ideally, patients can start buprenorphine without experiencing severe withdrawal. If they used heroin or other opioids, they might have to wait 12 hours to a couple of days after their last use before taking the medication.

But with fentanyl, the wait is far longer. And if buprenorphine is started too soon, it can throw a patient into severe withdrawal – and back to fentanyl use.

'I call fentanyl sticky'

Fentanyl stays in a person's body, on the brain's mu opioid receptors, longer than other opioids do.

"I call fentanyl sticky because it hangs onto the receptors so long," said Dr. Mina "Mike" Kalfas, a certified addiction expert with St. Elizabeth Healthcare's Journey Recovery Center in Northern Kentucky. "It's just the nature of the drug. Every drug has its unique action at the (mu opioid) receptor, and this is unique to fentanyl."

Kalfas started treating patients with Suboxone nearly 20 years ago – when the medication was new. Prescription painkiller misuse was escalating in Kentucky and heroin was edging onto the scene. He started with a half-dozen Suboxone patients and has progressed to up to about 250 at any given time for whom he prescribes the drug.

Now, most of them come in to be treated for fentanyl addiction.

And Kalfas is seeing a new problem: Patients addicted to fentanyl have to wait longer to start the medication regiment, he said. That means enduring days in withdrawal. Because if they are given buprenorphine too soon or at doses that are too high, they may experience excruciating withdrawal, known medically as precipitated withdrawal.

The symptoms are so bad that they can chase people with opioid use disorder back to using.

"The problem is, once they start to withdraw, they run," Kalfas said. "They feel terrible, because withdrawal is the thing that they are most afraid of."

Fentanyl provides a unique challenge to public health, treatment

It's a situation that opioid addiction experts have been aware of for a few years, as fentanyl has overtaken heroin and been found in an array of other drugs that are misused.

Dr. Adam Bisaga, a Columbia University addiction research specialist, pointed out in a 2019 report that the replacement of heroin use with non-pharmaceutical fentanyl "poses unique challenges for public health and treatment professionals." He said clinicians were reporting problems with patients experiencing delayed or precipitated withdrawal as they were induced with buprenorphine.

"New strategies to decrease mortality among users of opioids are urgently needed," Bisaga wrote. "Research programs should be established to rapidly generate evidence to guide interventions directed at individuals affected by the influx of fentanyl."

Kalfas, who is certified to treat up to 275 patients with buprenorphine, said he's seen people with fentanyl in their system for days after their final use of the drug. Avoiding withdrawal as they begin their medication can be a struggle, he said, and if they don't make it through the wait, their desire to get help is destroyed and they are again in danger of overdosing. It can be even worse to induce buprenorphine if it's too soon to do so safely.

"Once I precipitate them severely enough, I’ve lost them," Kalfas said. "I’ve lost their trust, I’ve set them back in their decision-making, and they usually leave if they get precipitated here."

Here's what else Kalfas had to say about our fentanyl questions

Answers have been edited for brevity and clarity.

Some patients say they have trouble getting free of fentanyl weeks after they've not used it. Is that possible?

Kalfas: Yes. Norfentanyl is a major fentanyl metabolite which does not cause euphoria. It can stay on receptors in the central nervous system for weeks. It is barely detectable.

Have you seen any patients who have mistakenly taken fentanyl pills, thinking they're a prescription medication?

Kalfas: Yes. For example, I had a guy come in and say, he took a 'couple oxys' for a back problem. I said, 'That's odd, there's no oxycodone in your urine. It's all fentanyl.' The patient was stunned.

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Does Journey Recovery see a lot of people who primarily use fentanyl?

Kalfas: Yes. Every provider has new patient (buprenorphine) induction appointments every day.

If I called for an appointment to begin opioid use disorder treatment, how long will it take to get one?

Kalfas: Usually, if you call in the morning, we have you come in the afternoon.

Do you think treatment for addiction disorders needs to change?

Kalfas: Yes. Treatment has to evolve with use evolving. When we saw heroin, we wanted to treat heroin. When we see fentanyl, we want to treat fentanyl. We are always playing catchup. We need to treat addiction, not just an addiction to a particular drug.