Patients being treated for opioid addiction are experiencing more severe withdrawal symptoms as a result of fentanyl, a powerful drug, according to experts. Buprenorphine is a key medication used to treat opioid use disorder, and it appears to be particularly susceptible to fentanyl overdose.

Fentanyl is contributing to the country’s drug epidemic by making the world’s most-prescribed addiction drug unavailable to a large number of patients who are in need of it, even as overdose deaths soar.

 

Addiction doctor and psychiatry professor Sarah Kawasaki of Pennsylvania State University said that starting patients on buprenorphine therapy has become “progressively more challenging” over the past five years as fentanyl has become more widely distributed in the drug supply.

 

Kawasaki said that one of just two medications commonly used to treat opioid addiction, buprenorphine, makes matters worse. Patients can only get methadone, the other medication, at specialized clinics where they must appear in person each day to receive a single dose.

According to Kawasaki, having 20 methods to deal with strep throat but only two drugs to treat opioid addiction is a recipe for failure.

 

Doctors have reported that buprenorphine inductions have become harder in the United States and Canada, where fentanyl is also prevalent. It is difficult to measure or explain this phenomenon. Fentanyl’s raw power or its lipophilicity – it adheres to fat particles – and its tendency to stay in the body longer than other opioids are two theories.

 

Because of its unique structure as a partial opioid agonist, buprenorphine binds to the same receptors as opioids but does not fully engage them, resulting in a similar euphoric effect. It binds to the receptor in an awkward way, like a piece of a puzzle that doesn’t fit, so patients who are dependent on opioids are likely to experience “precipitated withdrawal” when their addiction medication dislodges the fentanyl.

 

Because of this, doctors frequently wait several hours before administering buprenorphine in order to prevent withdrawal symptoms. Once the “bupe,” as it’s known, is administered, it can treat withdrawal symptoms like anxiety or gastrointestinal distress as well as prevent future opioid cravings.

Doctors must wait a full day, if not longer, to ensure that buprenorphine doesn’t cause severe discomfort with fentanyl. Even patients who abstained from drugs for many hours, making them good candidates for buprenorphine, frequently experience worsening symptoms rather than improvement when they begin taking the medication. Many do not receive a second dose, known as a ‘failed induction.’

 

Physicians caution that such attempts may be dangerous—not just because they may cause patients to return to fentanyl use, but also because those patients might become so despondent that they would never want to try buprenorphine again.

 

Despite its disadvantages, some clinicians say patients have become more likely to request methadone. Because patients at Kawasaki’s clinic, which offers methadone and buprenorphine, have been reluctant to participate in a study about buprenorphine induction because they prefer the drug that causes fewer withdrawal symptoms, she has difficulty enrolling patients.

 

Despite its prevalence, doctors haven’t reached a consensus on how to proceed. Medical societies and local health officials haven’t provided much guidance, so doctors rely on word-of-mouth, email chains, and new scientific papers to informally guide them.

 

The Substance Abuse and Mental Health Services Administration recently released a statement that cautioned against the use of buprenorphine with fentanyl long-term and at high doses, noting that it may not be appropriate.

 

According to David Fiellin, an addiction physician and the director of Yale University’s Program in Addiction Medicine, there are a variety of induction approaches at this time. In many ways, we are in an area where there is not much science.

 

Fiellin recently issued a call in the Journal of Addiction Medicine for “rapid research” on the connection between drug type and quantity, and difficulty initiating buprenorphine treatment in recovering addicts.

 

Doctors, on the other hand, are employing strategies that vary significantly. Some have begun giving buprenorphine in radically larger amounts in an effort to overcome withdrawal symptoms through brute force—up to 32 milligrams, or four times a typical first dose.

 

Some doctors, including Kawasaki, treat remaining physical discomfort and anxiety symptoms by using common medications such as antihistamines, ibuprofen, and drugs to combat nausea and gastrointestinal difficulties.

According to Dr. Samantha Young of the British Columbia Centre for Substance Use, some people attempt to avoid an abrupt, large buprenorphine dose by microdosing buprenorphine over several days, in increasing quantities. Longer-acting painkillers such as hydromorphone are sometimes used to alleviate withdrawal symptoms as patients build up to higher buprenorphine doses, she said.

“ buprenorphine is an art based on science,” Young said when teaching residents and medical students about it.

 

Naloxone, a drug used to reverse opioid overdoses, has been administered to patients who are not overdosing, resulting in a very brief period of intense withdrawal, enabling patients to receive their first dose of buprenorphine, which alleviates discomfort rather than causing it.

 

Any strategy that works is welcome, Fiellin said. However, the fact that it has become more difficult for physicians to prescribe buprenorphine is worrisome in itself. Buprenorphine is a highly effective substance, but it is also strictly controlled, making it more difficult to convince non-addiction specialists to prescribe it. He fears that recent achievements could be reversed as a result.

 

Fiellin said that for about a decade or so, non-specialists weren’t seen as a threat to initiate buprenorphine use, so it was much more likely. Unfortunately, we’re in a place now where initiation is seen as a huge challenge, and I’m concerned that that will set us back when it comes to expanding the number of clinicians prescribing buprenorphine.

 

Physicians who are still optimistic believe that patients can still begin buprenorphine therapy. Patients shouldn’t be discouraged, they say. Despite the difficulties, buprenorphine induction is still possible for people using fentanyl. Because of the massive quantity of fentanyl in the North American drug market, induction is a bit more difficult, says Young. “However, we have developed a number of approaches—if you wish to begin bupe and you use fentanyl, you can. It is possible to begin bupe without you being in withdrawal.”