CDC Discloses Menacing Data on Methadone

According to newly released reports from the U.S. Centers for Disease Control and Prevention (CDC), the synthetic opioid methadone accounts for less than 2% of analgesic prescriptions but is involved in more than 30% of opioid-overdose deaths. However, in some ways, the selective analysis and presentation of data may be misleading.

Government researchers analyzed data on methadone in the United States from 1999 to 2010, and from 13 states in 2009 that were covered by the DAWN surveillance system for drug-related deaths (Drug Abuse Warning Network of the Substance Abuse and Mental Health Services Administration). The CDC released two documents presenting results:

• Prescription Painkiller Overdoses: Use and Abuse of Methadone as a Painkiller, CDC VitalSigns™, July 2012 [PDF here].
  
  
• Paulozzi LJ, Mack KA, Jones CM. Vital Signs: Risk for Overdose from Methadone Used for Pain Relief — United States, 1999-2010. MMWR (Morbidity and Mortality Weekly Report). 2012(Jul 3);61 [PDF here].

According to CDC data, methadone accounted for 4.4 million (1.7%) of the 257 million opioid analgesic prescriptions in 2009. At the same time, about 5,000 persons die each year of overdoses related to methadone, which accounts for approximately 30% of all deaths associated with prescription opioids. Methadone-related deaths reportedly increased 6-fold from 1999 to 2009.

Furthermore, the reports observe, 4 of every 10 overdose deaths involving a single prescription opioid relate to methadone, which is twice as many as with any other opioid analgesic. Methadone appears to carry greater risks than other opioids because it tends to build up in the body and can incur respiratory depression or, allegedly, cardiac rhythm disturbances.

CDC researchers stress that methadone has been used safely and effectively for decades in treating opioid addiction, and that modality does not appear to be part of the current problems. Rather, during the past decade methadone has been increasingly used as a pain reliever and, as prescriptions for pain have increased, so have methadone-related nonmedical use and fatal overdoses.

A press release from the CDC [here] comments that, despite recent federal efforts to warn health care providers that methadone prescribing is complex and that methadone should not be a first-choice analgesic, the number of methadone prescriptions has not declined significantly. “The majority of these prescriptions are written by practitioners who typically do not have special training in pain management,” according to the press release.

The CDC reports suggests that most methadone prescriptions have been written by primary care providers or mid-level clinicians (eg, nurse practitioners) rather than pain specialists. Additionally, nearly a third of prescriptions appear to have been for patients with no prior exposure to opioids (ie, opioid naïve), which requires special care during early stages of dosing and titration.

COMMENTARY: As usual, the CDC has at hand some dramatic and compelling data to support their ongoing campaign of warning the public about the harms of prescription analgesics — in this case, methadone. While the CDC’s precautions regarding this strong opioid are of importance, they neglect to mention in fair balance that methadone has special characteristics unlike other opioid agents that sometimes make it particularly effective. As clinicians often acknowledge, methadone sometimes works in relieving moderate to severe pain of many types even when all other analgesics have failed.

As in past reports of this nature from the CDC, the authors have put together a visualization of the methadone crisis that is informative and misleading at the same time [see graph]. The implication is that there has been a direct correlation of methadone analgesic prescribing and use with overdose deaths.

In actuality, the graph might portray a common fallacy in medical research, called cum hoc, ergo propter hoc, or “with this, therefore because of this.” This wrongly reasons that when two or more event rates or trends seem to change in parallel there automatically is a cause-effect relationship between them, and we have discussed this concern with similarly questionable CDC data presentations in the past [see UPDATE here].

For example, the data do not tell us if overdose deaths were primarily (a) in patients who either were misprescribed or misused their methadone, or (b) among persons who were abusing diverted or illicit methadone. Both situations are problematic, but they have different origins and require individual solutions. Patients with pain should not be denied methadone if most of the problems are stemming from the reckless misbehaviors of other persons.

The CDC concedes that its mortality data might be skewed to begin with, because there is no uniformly applied definition of drug-related deaths or for attributing causality to particular agents. Also, in the latest year reported, methadone mortality accounted for only about 0.2% of all deaths in the U.S. population; not zero, but hardly the epidemic claimed by government agencies and other groups. [See mortality data in National Vital Statistics Reports, PDF here].

Of greatest importance, the graph shows a downward trend beginning in about 2007 (5 years ago) that could be significant and still continuing in a favorable direction today (since the CDC has not looked beyond 2009 in mortality data). This relates to several possible reasons for the adverse upward trends at the outset (some of which are acknowledged in the CDC reports):

• First, the initial product labeling for methadone as an analgesic suggested dangerously high starting doses of up to 80 mg/day. This was finally revised in October 2006 to require starting opioid-naïve patients on oral methadone at doses of 2.5 to 10 mg every 8-12 hours, or 30 mg/day maximum, slowly titrated to effect. This alone, may have accounted for declining mortality trends that are still continuing today.
  
  
• Second, since methadone is among the least expensive opioid analgesics, some institutional and insurance formularies listed it as a preferred analgesic, and inadequately trained clinicians were encouraged to prescribe methadone. As the harms of this approach have become better recognized, this practice has been slowly discontinued.
  
  
• Third, healthcare providers, patients, and the public were not adequately educated and warned about methadone’s idiosyncrasies, particularly regarding its long and variable elimination half-life that can lead to physiological accumulation and toxicity. For example, patients or illicit users who are not achieving desired effects from methadone might increase the usual dose and/or frequency, which could be tolerable with some opioids but can be toxic with methadone; and, there may be a deceptively delayed onset of methadone adverse effects, making it especially lethal.
  
  In more recent years, there has been improved education on methadone, including via our Pain-Topics offerings on this subject [here]. So, prescribers and their patients (perhaps, even “street addicts”) are more attuned to safety concerns, which may be contributing to declining mortality even as methadone prescribing and use remain at relatively high levels.

This is not to say that problems surrounding methadone have been resolved and trends will continue to diminish unabated. However, it is unfortunate that agencies like the CDC feel motivated to present data in the most unfavorable and unbalanced light in a drive to stir public awareness and condemnation.

Finally, we must object to the CDC’s frequent and liberal use of the term “painkiller” in reference to opioid pain relievers in their reports and other communications to the public. For one thing, this term wrongly implies that these drugs put a permanent end to pain (ie, kill it), which is inaccurate since opioids only offer temporary relief. Secondly, there is a subtle implication that opioids are broadly lethal medications (ie, killer drugs), which is highly biased and inflammatory.

News media look toward official sources, such as press releases from government agencies, for the terminology they should use, so the government’s use of “painkiller” is adopted by reporters and ends up conveying both incorrect and slanted perceptions to the public. Most perniciously, the CDC knows better [as we have noted previously here], because they exclusively use the more correct “opioid analgesic” or “pain reliever” in their communications to healthcare professionals.

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