Naloxone Is Cost-effective Way to Prevent Heroin Overdose Deaths

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Distributing naloxone more widely to heroin users would reduce the number of deaths due to overdose and would be a cost-effective intervention, according to a mathematical model described in the January 1, 2013,Annals of Internal Medicine. Providing naloxone to prescription opiate users would prevent even more deaths.

Accidental death due to respiratory depression is a risk for people who use heroin and other opiates including prescription painkillers. Rates of fatal drug overdoses have more than doubled in the U.S. over the past decade, and it is now the leading cause of preventable injury death.

Naloxone (marketed as Narcan and other brand names) is an opioid antagonist that works by blocking the body's endogenous opiate receptors so heroin cannot and other opiates cannot exert their effects. Since naloxone immediately halts the action of opiates, it causes very unpleasant symptoms of abrupt withdrawal.

Traditionally only emergency first responders and other medical personnel have been legally permitted to administer naloxone. But syringe exchanges and other harm reduction programs have started to distribute it more widely in an effort to reduce overdose deaths, especially in situations where people who use drugs are reluctant to call for help due to fear of legal consequences.

As of 2010, nearly 200 public health programs around the country had trained more than 53,000 individuals how to use naloxone, according to a press release issued by the San Francisco Department of Public Health (SFDPH), which runs one such program. Together these programs have documented more than 10,000 cases of successful overdose reversals.

Phillip Coffin from SFDPH and Sean Sullivan from the University of Washington in Seattle estimated the cost-effectiveness of distributing naloxone to lay people such community health outreach workers and drug users themselves so they can administer it when they witness an overdose.

The researchers devised a computer simulation (integrated Markov and decision analytic model using deterministic and probabilistic analyses) to predict the outcome of widespread naloxone distribution. They used epidemiological data from published literature about factors such as how many overdoses occur and how often emergency medical services are activated. They ran their model for a hypothetical 21-year-old novice heroin user in the U.S., as well as more experienced users, taking into account the possibility of repeat overdoses.

The study authors then calculated how much it would cost to save a year of life. They used a typical program cost of $6 per dose or $15 per kit of injectable naloxone, with a baseline cost of $25 per kit including staff time and other distribution costs. They looked at increases in quality-adjusted life-years, or QALYs. Typically a QALY gain is regarded as an economic benefit; policymakers have traditionally considered an incremental cost of less than $50,000 per QALY to be cost-effective. However, the researchers also did a secondary analysis assuming heroin users are a net cost to society.

Results

Based on these findings, the researchers concluded, "Naloxone distribution to heroin users is likely to reduce overdose deaths and is cost-effective, even under markedly conservative assumptions."

In general, confidence intervals were wide in these analyses, indicating a high degree of uncertainly, due to the shortage of relevant data to feed the model. The simulation was not able to account for other potential benefits of expanded naloxone distribution, such as reduced drug use or healthier habits resulting from peer education.

"Although the absence of randomized trial data on naloxone distribution and reliance on epidemiologic data increase the uncertainty of results, there are few or no scenarios in which naloxone would not be expected to increase quality-adjusted life-years at a cost much less than the standard threshold for cost-effective health care interventions," they elaborated in their discussion.

Real-world data suggest that naloxone distribution may have greater benefits than those predicted by the model, the authors added, noting that reductions in community-level overdose mortality ranging from about 40% to 90% have been seen following expanded naloxone distribution in Chicago, Massachusetts, New York City, San Francisco, and Scotland.

In San Francisco, where naloxone distribution stared in the late 1990s, heroin overdose fatalities have decreased from a peak of 155 in 1995 to 10 in 2010, according to a SFDPH press release describing the study findings.

"Naloxone is a highly cost-effective way to prevent overdose deaths," Coffin said in the press release, which noted that the cost per QALY of naloxone distribution is less than that of many well-accepted prevention programs, and is similar to the cost-effectiveness of smoking cessation interventions or blood pressure monitoring.

In an accompanying editorial, Wilson Compton and Nora Volkow from the National Institute on Drug Abuse (NIDA) and Douglas Throckmorton and Peter Lurie from the Food and Drug Administration (FDA) described an April 2012 meeting sponsored by NIDA, the FDA, the Centers for Disease Control and Prevention (CDC), and the Office of the Assistant Secretary for Health to discuss expanded access to naloxone, particularly outside conventional medical settings.

While naloxone is considered safe, one factor limiting its widespread use by lay people is that the only approved formulation must be injected with a needle. This raises concerns about the need for training and running afoul of drug paraphernalia laws.

Potential alternatives under study include intranasal formulations (currently available "off-label") or an auto-injector (such as the Epi-pen used to administer epinephrine for anaphylactic reactions). Another possibility being explored by NIDA is a device that would deliver naloxone automatically when oxygen levels fall below a threshold signaling respiratory depression.

The editorial authors emphasized that most of the increase in overdose deaths in recent years is related to prescription opiates such as hydrocodone, oxycodone (OxyContin), or combinations with acetaminophen like Vicodin. These include both patients taking excessive doses of medications prescribed to them for legitimate indications and drugs obtained fraudulently or diverted into the underground market.

The SFDPH press release noted that mortality due to opioid analgesics has remained high in San Francisco -- accounting for 121 deaths in 2010 -- even as heroin overdose deaths have dropped.

"Studies of the use of take-home naloxone for persons receiving high dosages of prescription opioids and of those abusing the drugs are warranted to determine whether such interventions reduce mortality and morbidity," Compton and colleagues wrote. "In particular, studying the effectiveness of layperson-administered naloxone in reversing overdose from long-acting and extended-release opioids is essential."

Coffin and Sullivan explained that they did not do a similar analysis of prescription opiate analgesic users as they did for heroin users because of lack of data or substantial uncertainty about important parameters such as proportions of first-time and subsequent overdoses, likelihood of witnessed overdose, or use of emergency medical services.

Nevertheless, they wrote, "naloxone distribution targeting opioid analgesic users has been associated with similar reductions in mortality...suggesting similar health benefits."

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References

PO Coffin and SD Sullivan. Cost-Effectiveness of Distributing Naloxone to Heroin Users for Lay Overdose Reversal. Annals of Internal Medicine 158(1):1-9. January 1, 2013.

WM Compton, ND Volkow, DC Throckmorton, and P Lurie. Expanded Access to Opioid Overdose Intervention: Research, Practice, and Policy Needs. Annals of Internal Medicine 158(1):65-66. January 1, 2013.

Other Source

San Francisco Department of Public Health. Study Shows Naloxone Cost-Effective in Preventing Overdose Deaths. Press release. December 31, 2012.