Tuesday, February 21, 2012

Naloxone Saves Lives, But Pain Patients Left Out

CDC Logo Drug overdose deaths have risen dramatically in the United States, with fatalities involving prescription opioids and illicit heroin prominently implicated. However, since the mid-1990s a small number of community-based programs have offered naloxone — a medication approved since 1971 that reverses the often fatal effects of opioid overdose — to illicit-drug abusers and their families and friends. According to new data from the from the U.S. Centers for Disease Control and Prevention (CDC) the number of at-home overdose rescues using naloxone has been remarkable; yet, patients prescribed opioids for pain rarely have access to this potentially lifesaving medication.

Writing in the February 16, 2012 edition of MMWR (Morbidity & Mortality Weekly Report) from the CDC, Eliza Wheeler, MPA, of the Harm Reduction Coalition, and colleagues report a first-ever survey of community-based opioid overdose prevention programs that provide naloxone for at-home use [Wheeler et al. 2012]. In October 2010 the researchers contacted 50 programs known to distribute naloxone in the U.S., and received responses from 48 programs that have 188 separate distribution locations.

The first naloxone distribution programs started operations in 1996 and have increased in number through the years to include locations in 15 states and the District of Columbia. However, many states with high drug overdose death rates have no or few opioid overdose prevention programs that distribute naloxone. For example, there are no locations in Florida, Ohio, or West Virginia, and only 2 in Washington State. The states with the most distribution locations include New York (65 locations), New Mexico (56), California (17), Wisconsin (16), and Illinois (10).

According to the MMWR article, from 1996 through June 2010 the relatively small number of existing programs provided naloxone, along with training in its use, to a total of 53,031 persons, resulting in 10,171 reversals of opioid overdose using the medication. It is believed, however, that the numbers of program participants and overdose reversals probably are underestimated because of incomplete data collection and unreported overdose reversals.

The researchers note that most programs (88%) distribute naloxone for injection — providing needled syringes and vials of the medication — while 8% provide naloxone adapted for intranasal administration (using an atomizer tip on the syringe that creates a nose spray), and a small number provide both forms. Many of the distribution programs (44%) reported difficulties obtaining naloxone due to supply shortages and costs relative to available funding.

The recommendation coming from this report is that, “to address high rates of opioid drug overdose deaths, public health agencies could, as part of a comprehensive prevention program, implement community-based opioid drug overdose prevention programs, including training and providing naloxone to potential overdose witnesses, and systematically assess the impact of these programs.” This sounds good and reasonable — what is the delay?

COMMENTARY: We have previously written in these UPDATES about naloxone for at-home overdose rescue [eg, here and here] and in a journal article [PDF here]. As noted above, naloxone is nothing new; it is an opioid antagonist that has been approved and used in the U.S. since 1971 as an antidote to respiratory failure during opioid overdose.

Until the first community-based overdose prevention programs started distributing naloxone for at-home use in 1996, it was administered exclusively in emergency departments or by first-responder emergency personnel; sometimes too late to save lives. This new survey provides convincing data about the potential successes of naloxone distribution to the public.

With roughly 10,200 overdose reversals among 53,000 participants this suggests an exceptional NNT=5. That is, for every 5 persons receiving naloxone for emergency use there was at least 1 reversal of life-threatening overdose. Granted, it cannot be stated with certainty that each of those overdoses would have been fatal if untreated.

Naloxone Rescue Still, using data from the survey, the researchers compare the numbers of programs starting naloxone distribution each year during 1996 to 2010 with the increasing annual rate of unintentional opioid overdose deaths from earlier CDC data. The figure at right is adapted from their report.

It is important to observe that the death rate started to level off in about 2006, when there were about 28 naloxone distribution programs. This number might have achieved some sort of critical mass for affecting the trend; although, it is not known at present if that plateau or even a declining trend has continued during the past couple of years.

Also of importance, the naloxone distribution programs were originally started within “needle exchange” and other harm reduction programs serving substance-abusing persons who inject drugs, and this has persisted through the years. According to the lead author of the MMWR article, Eliza Wheeler [personal communication 2/20/2012], participants in the surveyed opioid overdose prevention programs were almost exclusively injection-drug abusers, involving heroin and other opioids. Therefore, everyday patients prescribed opioids for pain conditions were for the most part not being served, with the exception of a small program in rural North Carolina — Project Lazarus [discussed previously in an UPDATE here].

So, why have the many millions of patients with chronic pain conditions who are prescribed long-term opioids been left out?

This is quite puzzling, especially since an earlier report from the CDC [see UPDATE here] described the nearly 15,000 opioid-related deaths in 2008 alone as an “epidemic.” Widespread naloxone distribution — given to patients and their family caregivers with every prescription for long-term opioid analgesics — would be a most direct way to help avert overdose deaths and a mitigation strategy that does not threaten ongoing access to opioid medication for legitimate patients with pain. However, it is almost as if the CDC, along with other government agencies at federal and state levels, would rather complain about the overdose problem than do something immediate and substantive to curtail it.

Opponents of naloxone cite fears that providing it to patients will only encourage them to misuse their opioid analgesics, knowing there is a safety net nearby to save them if they take too much medication. However, this is like saying that putting seat belts and air bags in automobiles only encourages people to drive recklessly. While risky behavior is possible in either case, there is no credible research evidence to support a contention that making harm reduction measures available promotes such irresponsibility. Meanwhile, innumerable live are or might be saved by such safety strategies.

As we noted last November, 2011 [UPDATE here], the U.S. Food and Drug Administration (FDA) has finally called for a workshop meeting to “discuss whether naloxone should be made more widely available to trained, non-healthcare individuals in an effort to significantly reduce deaths due to opioid overdose.” Never ones to move hastily, the meeting will not be until this April 12, 2012, and then the outcome is uncertain since there are numerous barriers.

For one thing, an approach other than giving patients syringes, needles, and vials of naloxone is needed. While filling and using needled syringes may be familiar to injection-drug abusers, most patients with pain and their family caregivers would be aghast at the thought of using such paraphernalia even in an emergency.

One solution would be providing an intranasal kit, which merely requires attaching an atomizer tip to a prefilled syringe of naloxone and spraying it up the victim’s nose; something a child could be taught in advance with 10 minutes of instruction. It could even be used to rescue a family pet that has accidentally ingested a patient’s opioid medication. Another method might be a naloxone auto-injector device, perhaps similar to the familiar EpiPen® for injecting epinephrine to thwart allergic reactions. Last fall, the U.S. National Institute on Drug Abuse (NIDA) was seeking proposals to develop a sophisticated device along these lines [discussed in UPDATE here].

Intranasal naloxone and auto-injectors containing the drug are not currently FDA approved and would require a sponsoring manufacturer to seek such approval, and then arrange for product development and distribution. Unless some sort of accelerated program is put in place, it could be some years before a practical naloxone at-home overdose rescue kit is in the hands of every patient with chronic pain who receives a prescription for opioid analgesics. Meanwhile, although the trend in fatal opioid overdoses may hopefully stay level or somewhat decline, a great many persons will die who might otherwise be saved — and it could be you or someone you love.

REFERENCE: Wheeler E, Davidson PJ, Jones TS, Irwin KS. Community-Based Opioid Overdose Prevention Programs Providing Naloxone — United States, 2010. MMWR (Morbidity & Mortality Weekly Report). 2012(Feb 17);61(6):101-105 [article PDF available here].