Conference Coverage

Understanding properties of fentanyl, other opioids key to treatment

Naloxone increasingly coming up short, expert says



– Treating disorders tied to the use of highly potent synthetic opioids (HPSO), such as fentanyl, is challenging at best, an expert said at the annual meeting of the American Academy of Addiction Psychiatry.

Dr. John J. Mariani, associate professor of clinical psychiatry at Columbia University, New York

Dr. John J. Mariani

“We have essentially no data to guide pharmacotherapy management decisions for the leading cause of fatal overdose deaths in the U.S.,” said John J. Mariani, MD, associate professor of clinical psychiatry at Columbia University, New York. “In the absence of data to make evidence-based recommendations, we still need to treat patients.”

That means taking what is known about the properties of those drugs into account when making treatment decisions, he said. Fentanyl quickly crosses the blood-brain barrier and is rapidly distributed to peripheral tissue. It has a short duration of action, but its duration can be extended with multiple injections or an infusion, he said. Research suggests that it has opioid receptor affinity similar to that of morphine, and it’s not known why it is up to 100 times more potent than morphine.

From his own experience, he offered some suggestions on treating patients who use HPSOs:

  • Buprenorphine: Clinicians using buprenorphine as induction treatment have to wait longer from the last use to the first dose because of its longer effective half-life, and other medications might be needed to manage withdrawal. For maintenance, higher doses possibly should be considered to prevent HPSO override and to maintain opioid tolerance.
  • Extended-release naltrexone: This involves a more difficult induction, and there is a question of whether inpatient treatment is better than outpatient, he said. For maintenance, more frequent administration should be considered, with closer monitoring for the risk of override and more urine toxicology testing.
  • Methadone: For induction, methadone could offer an advantage over buprenorphine, because there is no risk of precipitated withdrawal. For maintenance, Dr. Mariani said, it’s not known whether standard doses protect against raising tolerance out of the reach of HPSOs’ effects.
  • Naloxone: He said there have been increasing reports of multiple doses being needed to reverse an overdose. Because of the shorter time between substance use and death with fentanyl, more reports have been filed on unsuccessful attempts to revive people with naloxone despite multiple doses or stronger doses. Some naloxone programs have been giving more than two standard doses or using devices that give higher doses, he said. Also, since many users never intend to take fentanyl but are exposed to it through what they thought was heroin, communication is vital, he said.

Addiction psychiatrists “need to educate patients, families, and other clinicians of this new risk of using opioids,” he said.

Meanwhile, in another talk, Thomas Kosten, MD, described progress in the efforts to develop a vaccine against fentanyl addiction, in the hopes of preventing overdoses. Researchers are taking cues from the failed attempt to develop a cocaine vaccine a few years ago, in which not enough antibodies were produced in about half the patients.

Dr. Thomas Kosten, professor of psychiatry at Baylor College of Medicine, Houston

Dr. Thomas Kosten

This time, researchers are using toll-like receptor agonists to boost the effects of the main vaccine component, known as norcocaine. Those agonists can more than double the antibody increase that is seen without them, said Dr. Kosten, professor of psychiatry at Baylor College of Medicine, Houston.

So far, researchers have found that the vaccine produces blockade of fentanyl analgesia and respiratory depression in rats. Dr. Kosten said his lab is looking for funding to continue the research. “It looks like we’re going to have some money in February to start making the vaccine,” he said.

Dr. Mariani and Dr. Kosten reported no relevant disclosures.

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