Improving Access to Naloxone — Yes, Pharmacists (Nar)CAN!

Author(s)
Scott A. Coon, PharmD, BCPS, BCACP
Matthew Thomas, PharmD

Reviewed By
Lucas Hill, Pharm.D., BCPS, BCACP
Jordan L. Wulz, PharmD, MPH, BC-ADM, CHC\

Citation
Abouk R, Pacula RL, Powell D. Association Between State Laws Facilitating Pharmacy Distribution of Naloxone and Risk of Fatal Overdose. JAMA Intern Med. 2019; 179: 805-11.

The Problem

 

The opioid overdose epidemic, primarily driven by potent synthetic opioids, has rapidly intensified in recent years. According to the Centers for Disease Control and Prevention, there were over 47,000 fatal opioid overdoses in 2017 – a number that now rivals the number of suicide-related deaths in the United States.¹ Overdose education and naloxone distribution (OEND) efforts appear to have a positive impact on opioid-overdose mortality.² As many states continue to expand naloxone access through various legislation efforts, it’s important to identify which laws have the greatest impact on reducing fatal opioid overdoses.

 

What’s Known

 

Naloxone Access Laws (NALs), which include civil and/or criminal immunity to healthcare providers and laypersons who administer naloxone as well as laws increasing public access to naloxone products, are associated with significant increases in naloxone dispensing from community pharmacies.³ However, the impact NALs have had on opioid overdose deaths is less clear. Two recent studies found that NALs and Good Samaritan laws, which provide legal immunity to persons experiencing or acting during an overdose, had a positive impact on opioid overdose mortality.^4,5 On the other hand, a third study found that broadening naloxone access increased opioid-related emergency room visits but did not reduce mortality.⁶ Differences in study design likely explain these inconsistent findings.  State-by-state variability in NALs (i.e. more versus less restrictive NALs) and the rate of implementation of NALs at the ground-level are two important confounders. Implementation is particularly challenging. Even states with very permissive NALs, whereby pharmacists have the authority to dispense naloxone without a prescription, practice change has been slow. For example, fewer than 25% of pharmacies in California reported dispensing naloxone without a prescription in the two years after the state adopted a relatively permissive NAL.⁷ Thus, the impact of NALs on overdose mortality may be due to differences in how laws are operationalized.

 

What’s New

 

Researchers at the William Paterson University, the National Bureau of Economic Research, and the RAND Corporation recently performed a comprehensive nation-wide evaluation of the impact of NALs on fatal and nonfatal opioid overdose.⁸ To measure their primary outcome, investigators used the National Vital Statistics System for opioid-related mortality data (2005-2016), aggregated by state and month. Data regarding nonfatal opioid-related emergency department visits was obtained from state emergency department databases (2005-2016). Naloxone dispensing was tracked using state drug utilization data from Medicaid claims (2010-2016). Finally, a mix of legal and academic sources were used to categorize NALs into three distinct groups:

1. Direct authority: pharmacists have explicit permission to dispense naloxone by having prescriptive authority or by not requiring a prescription.
2. Indirect authority: pharmacists are able to dispense through standing orders or statewide protocols.
3. Weak laws: any other naloxone laws providing protections other than those in the first two categories.

 

Table 1. Types of Pharmacist Authority NALs by State (in 2016)
Direct authority	Indirect authority	Weak laws
AK, CA, CT, ID, NM, ND, OK, OR, SC	AL, AR, CO,  DE, FL, GA, HI, IL, IN, IA, KY, LA, ME, MD, MA, MN, MS, MO, NV, NH, NJ, NY, NC, OH, PA, RI, SD, TN, TX, UT, VT, VA, WA, WV, WI	MI, NE
States are counted once for the most expansive set of laws. States without NALs at the time of the study: AZ, KS, MT, WY

 

For statistical analysis of the primary outcome, a difference-in-differences strategy was used. Fatal opioid overdose rates among the different NAL groups were compared to themselves relative to time from adoption (event estimates were normalized to 0 in the year of adoption). Investigators also measured and controlled for a variety of potential confounders. All outcomes were observed for three years post-adoption to account for the time it may take for NALs to be implemented. The impact of NALs on fatal opioid overdose rates at year three post-adoption is summarized in Table 2.

 

Table 2. Impact of NALs on fatal opioid overdose
Type of NAL	Change in fatal overdose rate per 100,000 population*	95% CI	P-value
Direct authority	-0.387	-0.119 to -0.656	0.007
Indirect authority	0.121	-0.014 to 0.257	0.09
Weak NAL	0.094	-0.040 to 0.227	0.17

*Estimated coefficients are at 3 years post-adoption

 

Results indicate that states that empowered pharmacists with direct authority to dispense naloxone saw a significant reduction in fatal opioid overdose rate (0.378 fewer per 100,000 population; p=0.007).  In the other NAL groups there was no change in fatal opioid overdose rates by the third year post-adoption. This corresponded to a fatal opioid overdose rate that was 34% lower in states with direct-authority NALs relative to those states that did not enact direct-authority laws. Notably, opioid-related emergency department visits increased in states with direct-authority NALs (45.446 nonfatal overdoses per 100,000 persons; p=0.045) — a 15% increase relative to states without direct authority. Surprisingly, there were no significant differences in naloxone dispensing rates among the three NAL groups.

 

Our Critical Appraisal

 

This study carefully examines the effects of NALs on opioid-related mortality and highlights the important role pharmacists play in OEND. Despite the challenges that come with retrospective studies that rely on existing databases, the difference-in-differences approach for comparing rates of fatal overdose was appropriate, as the data satisfied the necessary parallel trends assumption. Additionally, the authors controlled for numerous potential confounders, including differences between states with regard to prescription drug monitoring programs, Good Samaritan laws, medical marijuana laws, and unemployment rates.  Furthermore, Medicaid expansion was also factored into the analysis.

 

However, there are several limitations to consider.  The investigators limited the analysis to Medicaid claims only to estimate naloxone dispensing. The investigators indicate this dataset covers approximately 40% of nonelderly adults with opioid addiction, a particularly high-risk population to be sure, but naloxone access initiatives within the private sector may have also affected opioid overdose mortality rates. Investigators attempted to minimize this limitation by performing a separate analysis using data from managed care organizations, which yielded similar results. Also, while the investigators categorized NALs into three distinct groups, major differences in state NALs within these classifications make the groupings rather heterogeneous. For example, some states with indirect authority, NALs only permit pharmacists to dispense naloxone through standing orders in an inpatient setting. Other states with indirect NALs have far less restrictive statewide protocols, essentially allowing pharmacists in any setting to dispense naloxone.  The mixing of restrictive and expansive policies in one group may have diluted the overall impact some indirect authority NALs can have on opioid overdose mortality rates. Similarly, this study did not account for naloxone furnished outside of a pharmacy (i.e. non-pharmacy dispensing). This is a particularly important limitation, as there was no detectable change in naloxone dispensing from pharmacies in the direct NAL group, which is a key mediator between NALs and opioid overdose deaths. Thus, non-pharmacy dispensing may explain the reduction in mortality observed in states with direct NALs. Lastly, these results give us only a short-term glimpse of the impact of these laws and their benefits may require several years to materialize.

 

The study also found a significant increase in emergency department visits for nonfatal opioid overdoses in states with direct-authority laws. Some may point to this finding to argue that naloxone accessibility increases risky behavior. ⁹ This belief, sometimes held by healthcare professionals, law enforcement, and even persons who use drugs, has not been substantiated in the majority of studies published to date.⁹ Indeed, overdoses that would have been fatal (without naloxone access) become nonfatal events and result in more emergency department visits. Thus, the outcome of opioid overdoses are shifted from fatal to nonfatal. Furthermore, a culture in which naloxone access is widespread is thought to encourage persons to seek medical attention in general, as there is less fear of prosecution for illicit drug use.

 

The Bottom Line

 

These and other data support the notion that naloxone laws matter. Specifically, states which granted pharmacists direct authority to dispense naloxone without a prescription experienced a significant decrease in opioid-related overdoses.  The increase in nonfatal opioid overdoses represents opportunities to offer education and treatment, such as medication-assisted treatment. Community and ambulatory care pharmacists can have an impact by continuing to recognize opportunities to prescribe and dispense naloxone … and advocating for direct authority NALs for pharmacists.

 

The Key Points

• Direct authority NALs that allow pharmacists to dispense naloxone without a prescription are associated with a reduction in fatal opioid overdoses, while indirect authority NALs (e.g. statewide standing orders & protocols), are not.
• States that enact direct authority NALs may see an increase in ED visits for nonfatal overdoses, which should not be misconstrued as encouraging riskier behavior. States adopting direct authority NALs should proactively allocate resources to increase access to addiction treatment and harm reduction programs.
• Future research should evaluate the impact of eliminating barriers to naloxone (e.g. making naloxone over-the-counter).

 

FINAL NOTE:  This program will be available for recertification credit through the American Pharmacists Association (APhA) Ambulatory Care Review and Recertification Program.  To learn more, visit https://www.pharmacist.com/ambulatory-care-review-and-recertification-activities.