Synthetic Opioid Driving Overdose Death Rate

by Kayt Sukel

May 14, 2018


Currently, about 115 people in the US die each day from opioid overdoses, according to the Centers for Disease Control and Prevention (CDC). These individuals are casualties of the country’s opioid epidemic, a federal public health issue involving the abuse and overuse of prescription and illicit drugs including heroin, OxyContin (oxycodone), and Vicodin (hydrocodone). But since 2013, there have been a significant increase in overdose deaths involving one drug in particular, a synthetic opioid called fentanyl. A new study from researchers at the National Institute on Drug Abuse (NIDA) suggests this drug is involved in nearly half of all opioid-related overdose deaths.

Engineered for potency

Fentanyl, an analgesic (pain-relieving) drug, was developed as an anesthetic in 1959. In the decades since, it has been refined into a patch that can be easily stuck on the skin, allowing for quick, effective absorption. Fentanyl is what’s known as a synthetic drug, sometimes called a “designer” drug—one that was created using human-made chemical components as opposed to one made from naturally occurring ingredients. Ezekiel Fink, a neurologist and director of pain management at Houston Methodist hospital in Houston, Texas, says this is a synthetic drug that was engineered for maximum potency.

“This is a drug that is 50 to 100 times more potent than morphine. It is a synthetic drug, not something that was plant-derived or semi-synthetic, so the creators of this drug were able to really increase the pharmacologic properties of it in the lab,” Fink says.

Some of the changes to those pharmacologic properties include the increased potency for pain relief, an increased ability to cross the blood-brain barrier and enter brain tissue, an increased ability for the drug to be absorbed through the skin or the body’s mucosal surfaces, and a slower elimination of the drug from the body over time. Taken together, the changes to these properties significantly increase the risk of abuse for people who use fentanyl. Richard Friedman, a psychiatrist at Weill Cornell Medical College, calls it a highly addictive substance.

“Most drugs of abuse activate the receptors in the brain’s reward center. Fentanyl is incredibly addictive because of its increased potency,” says Friedman. “A drug like fentanyl produces a bigger, more potent signal to the brain. So the reward center reads that as, ‘This is important, don’t forget it.’ And users want it again and again.”

Fentanyl’s increased potency also increases the likelihood of overdose. Fink says that while most opioids are dosed out in milligrams, fentanyl is strong enough that you only need a few micrograms to get an effect.

“It doesn’t take much of this drug to overdose. And when it starts being used in a non-monitored setting, whether by itself or mixed in with other medications, it’s very easy to take too much,” he says. “That’s why we see more and more overdose deaths related to fentanyl, due both to off-label use for prescribed medications or illicit use of this drug.”

Nearly half of overdoses involve Fentanyl

That number of overdose deaths related to fentanyl is growing. In a recent NIDA study published in JAMA, the study authors found that fentanyl was involved in nearly half of the overdose deaths recorded by the National Vital Statistics System in 2016. Wilson Compton, deputy director of NIDA, says he was compelled to look at fentanyl’s role in overdose deaths as he heard from colleagues, more and more, that fentanyl might be playing an important role in the increasing drug overdose mortality numbers seen across the country.

“There’s been an outbreak of overdose deaths. We know that fentanyl is relatively inexpensive, increasingly available, and incredibly potent,” he says. “When we saw data coming out of CDC last December showing the frighteningly high rates of fentanyl deaths, we realized that it was a good opportunity to look at the overlap of fentanyl with other substances.”

Compton and colleagues looked at the data from overdose death certificates submitted by medical examiners and coroners between 2010-2016. They found that in the 42,249 opioid-related overdose deaths in 2016, 45.9 percent involved fentanyl. But even more surprising, many of those deaths also involved other substances.

“When you see the percentages across all the different substances, you realize just how widespread this problem is,” he says. “We saw fentanyl’s involvement in 40 percent of the cocaine deaths, 31 percent of the benzodiazepine deaths, and even 21 percent of antidepressant deaths. This drug is a poison—it’s readily available and wreaking havoc.”

Reducing overdose deaths

While it would be easy to blame these fentanyl-related deaths solely on overprescribing, a common issue in today’s opioid epidemic, Compton says that government agencies have not seen much of a change in the overall outpatient prescribing of fentanyl over the past few years. He thinks this increase in fentanyl-related deaths is likely more due to illicit use. Friedman agrees.

“Certainly, we are still dealing with inappropriate and over-prescribing of opioids, which remains an enormous problem that we need to address. But it’s becoming more obvious that fentanyl is becoming part of the illicit drug supply,” he says. “These drugs are easy to synthesize—and they are cheap to make. So you see it more and more on the streets.”

Compton emphasizes a need for better education about the effects of fentanyl, for physicians, first responders, and patients. He and his colleagues are also calling for expanded access to drug abuse treatment, as well as to naxolone, a drug that can help reverse the effects of opioid overdose. Fink says that it will take a multifaceted approach to deal with such a multifaceted problem.

“Because of fentanyl’s high potency, it can lead to massive problems whether it is prescribed or mixed in with other illicit drugs. People are not necessarily aware of what they are dealing with. They need to know—we need to educate them,” he says. “But it will take more than just education. The medical field needs to get away from the opioid-centric model for treating chronic pain and offer more multi-modal approaches. We need to destigmatize addiction and make treatment more accessible and affordable for people. We need to find ways to deal with fentanyl in illegal drug supplies, too. It’s going to require a huge paradigm shift and it needs to start now.”