CDC Addresses Fatal Opioid Overdoses, Offers Prescription Guidelines for Clinicians

CLINICAL CONTEXT
The number of prescriptions for methadone has risen substantially in the United States during the past decade. Advantages of methadone vs other opioids include its long duration of action, low cost, and availability in a liquid preparation. However, methadone also has multiple drug interactions, including serious interactions with other potential drugs of abuse.

Drug overdose with methadone is an increasing problem in the United States. Previous research has found that most cases of methadone overdose are unrelated to opioid addiction treatment. In fact, most patients with overdose had not even been prescribed methadone themselves. The current study from the US Centers for Disease Control and Prevention (CDC) examines the problem of fatal methadone overdose and provides recommendations to stem the tide of this rising public health issue.

STUDY SYNOPSIS AND PERSPECTIVE
Methadone played a central role in the epidemic of prescription painkiller overdoses that has emerged over the past decade, according to new research from the CDC.

CDC researchers looked at data from 1999-2010 and, using 2009 data from 13 states—those covered by a surveillance system for drug-related deaths, the Drug Abuse Warning Network of the Substance Abuse and Mental Health Services Administration—came up with some startling statistics.

Published in the July 3 issue of the CDC's Vital Signs, an early release of the Morbidity and Mortality Weekly Report, the research showed that

- Methadone contributed to almost 1 in 3 prescription painkiller deaths in 2009

- 6 times as many people died of methadone overdose in 2009 than a decade earlier

- About 5000 people die every year of overdose related to methadone, and a great majority of these cases are unintentional

- This represents more than 30% of prescription painkiller deaths, even though only 2% of painkiller prescriptions are for this drug

"The data are consistent over time and across different states, and they are consistent year to year," CDC director Thomas R. Frieden, MD, MPH, told reporters in a conference call. "We have seen a steady increase in prescription drug overdoses, and it matches very closely the steady increase in prescriptions for opiates."

According to Leonard J. Paulozzi, MD, MPH, medical epidemiologist from the Division of Unintentional Injury Prevention, at CDC's National Center for Injury Prevention and Control, regardless of where the information comes from—emergency departments or mortality data—all indications point to a "dramatic" increase in deaths overall for opioids, particularly for methadone.

Methadone Risky

Methadone, which has been prescribed safely and effectively for decades in the treatment of addiction, has recently been used increasingly as a pain reliever. Some prescriptions are obtained illegally or are used for nonmedical purposes—a practice known as diversion.

Unlike other drugs, methadone may build up in the body and disrupt respiration or cardiac rhythm. According to the CDC report, 4 of every 10 overdose deaths from a single prescription painkiller involved methadone—twice as many as any other prescription painkiller.

"Methadone is riskier than other prescription painkillers and it should only be used for pain when other drugs haven't been effective," said Dr. Frieden. "There are plenty of safer alternatives to methadone," he added, including other opiates, nonopioid drugs, and physical therapy.

"Since it's available as a generic drug, methadone may be less costly than other drugs, but using it comes with a huge human cost," said Dr. Frieden.

"Using methadone for pain is pennywise and pound foolish because although it may cost a couple of dollars less per pill, the result is many more emergency department visits and a much higher societal cost in deaths and addiction and other problems that can be avoided."

No Special Training

Federal efforts to warn healthcare providers that methadone should not be the first choice for pain relief have not significantly lowered the number of methadone prescriptions.

"The amount of methadone declined in recent years, but the number of prescriptions has not declined through 2009, so there's no indication that doctors are prescribing it less often; it's just that they're probably prescribing it at somewhat lower dosages," said Dr. Paulozzi. A majority of these prescriptions are written by practitioners who typically do not have special training in pain management.

According to Dr. Frieden, almost all states have some sort of prescription drug monitoring program.

"We are encouraged by some of the innovation and commitment we're seeing around the country," said Dr. Frieden. He used Oklahoma as an example of a state that has developed a "real-time" prescription drug monitoring program that posts information on its system almost immediately after a prescription has been written.

"Other states are doing more and more to reach out to doctors who may have problematic prescribing patterns to either educate them if it's an information gap or to take regulatory action if they are essentially selling prescriptions and, similarly, to identify patients who may be in need of treatment and encourage them to get treatment, or those who are using medication refills as a way of selling prescriptions, and to take appropriate action."

Provider Guidelines

According to the CDC, healthcare providers can help prevent prescription painkiller overdoses by adhering to the following guidelines:

- Screening and monitoring for substance abuse and other mental health problems

- Prescribing only the quantity needed based on the expected length of pain

- Using patient-provider agreements combined with urine drug tests for people taking methadone long term

- Using prescription drug monitoring programs to identify patients who are misusing or abusing methadone or other prescription painkillers, and

- Educating patients on how to safely use, store, and dispose of prescription painkillers and how to prevent and recognize overdoses

MMWR. 2012;61. Published online July 3, 2012. Abstract.

STUDY HIGHLIGHTS
Researchers evaluated data from the National Vital Statistics System between 1999 and 2009 for methadone-related deaths. A database from the Drug Enforcement Administration was used to track methadone prescriptions. Methadone use related to opioid treatment programs was not included in the study analysis.
The study also examined reports of drug-related deaths in 2009 from 13 states.
There was a steady increase in the number of prescriptions of methadone for pain between 1999 and 2008, at which time the total number of prescriptions leveled off. Methadone accounted for 1.7% of all opioid prescriptions in 2009.
There was a concomitant rise in the rate of methadone-related deaths during the study period. The mortality rate of methadone-related deaths peaked at 1.8 deaths per 100,000 persons in 2007.
State data demonstrated that methadone was associated with 31.4% of all opioid-related deaths, a figure well out of proportion to its percentage of opioid prescriptions.
Methadone was involved in 39.8% of single-drug deaths, more than twice the rate of any other opioid.
The authors of the current study make the following recommendations to prevent overdose with methadone:
Methadone should not be prescribed to opioid-naive patients.
Methadone should not be prescribed for mild pain or on an as-needed basis.
Most methadone prescriptions are written for musculoskeletal pain and headaches. These indications are generally inappropriate, and only practitioners with experience in prescribing methadone should be recommending the drug.
Insurers should require authorization for starting doses of methadone beyond the recommended upper limit of 30 mg/day.
Pharmaceutical companies should introduce a 2.5-mg dose of methadone.

CLINICAL IMPLICATIONS
The current study by the CDC demonstrates that the number of methadone prescriptions has increased during the past decade, with a commensurate disproportionate number of opioid-related deaths from methadone. This finding is particularly true for single-drug fatal overdoses.
Only practitioners experienced in pain management should prescribe methadone, and methadone should not be used for indications such as headache or back pain. Methadone should be prescribed only for patients who have received other opioids, and methadone should not be used on an as-needed basis.