The percentage of people treated for a drug overdose who need more than one dose of the opioid overdose antidote naloxone is on the rise, a new study suggests.

Researchers from the Centers for Disease Control and Prevention (CDC) analyzed data from the National Emergency Medical Services Information System, and found the percentage of patients receiving multiple naloxone doses among emergency medical service (EMS) responders increased from 14.5 percent in 2012 to 18.2 percent in 2015, which represents a 26 percent increase in four years.

“We found there were 31,000 cases in which two or more naloxone doses were needed in 2015 in a prehospital setting,” said lead author Mark Faul, PhD, Senior Health Scientist at the CDC. “Of those, 4,000 cases required three doses, 1,600 required four doses, 615 required five doses and 200 cases required six or more doses.” He noted that not all people requiring multiple naloxone doses were successfully revived.

The study was published in Prehospital Emergency Care. Dr. Faul discussed the results at the recent annual meeting of the American Public Health Association.

The study found patients ages 20 to 29 were most likely to need multiple naloxone administrations. Multiple doses were most common in the Northeast and Midwest.

Dr. Faul said that based on data from the Drug Enforcement Administration, there appears to be a connection between the areas where multiple naloxone administrations are increasing and areas where reports of fentanyl are on the rise. “We suspect that when fentanyl is involved, more naloxone administrations are required,” he said. Dr. Faul noted EMS responders on the scene do not know what substances a person has taken when they respond to a drug overdose.

Of all the instances in which naloxone was administered, only 16.7 percent of the 911 calls specifically identified the medical emergency as a drug ingestion or poisoning event, the study found. “If you are dispatching an ambulance, you need to know more about the nature of what the emergency is,” he said. “If responders know they are responding to a drug overdose, and it’s in an area with high rates of fentanyl, they can be better prepared with more naloxone and appropriate staffing.” It is possible that some callers are concerned about getting arrested for calling in a drug overdose, he said. He is now studying whether Good Samaritan laws, which provide legal protection for people reporting drug overdoses, are associated with an increase in the number of people who call in overdoses.

In October 2016, Dr. Faul spoke at a Food and Drug Administration (FDA) advisory committee meeting about increasing the standard dose of naloxone. “The basic formulations for naloxone haven’t changed since 1971,” he said.

The joint meeting of FDA’s Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee failed to produce consensus on the minimum dose of naloxone needed to reverse the effects of opioid overdose. At the meeting, 13 committee members agreed that the current injectable standard of 0.4 mg is effective and should remain in place, while 15 voted for a higher minimum dose based on the trend toward increasing use of more powerful opioids. Voters on both sides said they lacked enough evidence to make an informed decision.