New APS Guideline on Safe Use of Methadone

Megan Brooks

May 22, 2014

Measures can be taken to promote safer user of methadone, including better physician education and patient counseling about methadone safety and cardiac monitoring to identify patients at high risk for these problems, a new Clinical Practice Guideline on Methadone Safety from the American Pain Society (APS) concludes.

The safety of methadone, a synthetic opioid narcotic used to treat opioid addiction and chronic pain, has been questioned in recent years, as deaths from methadone overdoses have jumped from 800 in 1999 to 4900 in 2008, the authors note. The increase in deaths has been substantially higher than for any other opioid medication and is attributed to a sharp rise in prescribing methadone for chronic pain, they point out.

"The guideline was prompted by serious concerns about the great increase in number of methadone-associated overdose deaths," lead author Roger Chou, MD,  from the Oregon Health & Science University in Portland and head of the APS Clinical Practice Guideline Program, told Medscape Medical News.

"The unique properties of methadone — including its long and variable half-life, and association with QTc prolongation and ventricular arrhythmias — can make it difficult to use, and the guideline is meant to help clinicians prescribe more safely," he said.

"Although there are some other guidelines out there, all of them focused on the arrhythmia issue, even though it is probably responsible for only a small minority of deaths," he said. "This guideline also addresses safety issues related to dose initiation, titration, follow-up, and monitoring to prevent accidental methadone overdose. It is also the first guideline on methadone safety to be sponsored by professional societies related to pain (the American Pain Society) as well as addiction (the College on Problems of Drug Dependence, CPDD)," Dr. Chou explained.

The guideline is published in the April issue of The Journal of Pain.

Toward Safer Prescribing

The new document is based on a systematic review of the evidence on methadone safety performed by an interdisciplinary panel, commissioned by the APS and CPDD, in collaboration with the Heart Rhythm Society, under the direction of the Oregon Evidence-based Practice Center.

The panel identified "numerous research gaps" and note that most recommendations are based on low-quality evidence and none are based on high-quality evidence.

Among the key recommendations:

  • Patient assessment: Perform an individualized medical and behavioral risk evaluation to assess risks and benefits of methadone. Use the results to stratify patients according to their risk for substance abuse and consideration that the long and variable half-life of the drug could cause reactions with other prescription medications and possible arrhythmias. "Proper patient selection is critical when considering the use of any opioid, whether for chronic pain or treatment of addiction," the authors say.

  • Education and counseling:  Counsel patients about potential risks and benefits before initiating methadone therapy. Advise patients to take methadone as prescribed and comply with recommended follow-up and monitoring. Notify caregivers about risks for respiratory depression; include instructions to withhold additional doses of methadone and contact the prescriber if signs of respiratory depression or somnolence occur.

  • Baseline electrocardiogram (ECG): Obtain an ECG before initiating methadone therapy in patients with risk factors for prolonged corrected QT interval (QTc), any prior ECG demonstrating a QTc greater than 450 ms, or a history suggestive of prior ventricular arrhythmia. Consider obtaining an ECG before starting methadone in patients not known to be at higher risk for prolonged QTc. Recent data suggest that methadone is the most common drug-related cause of ventricular arrhythmia, the panel notes.

  • Alternative medications: Consider buprenorphine as an option for patients being treated for opioid addiction who have risk factors for prolonged QTc.

  • Low beginning dose: Start methadone at low doses (no more than 30 to 40 mg daily) and titrate slowly. This recommendation is based on the drug's long and variable half-life, which can be as long as 120 hours. Slow titration may reduce the risk for unintended drug accumulation and accidental overdose, the panel says.

  • Urine drug testing: Perform urine drug testing before starting methadone therapy and at regular intervals for patients treated for opioid addiction.

"The take-home message," Dr. Chou told Medscape Medical News, "is that methadone needs to be prescribed cautiously and that clinicians need to understand its unique properties. 

"There are steps that can be taken to mitigate risks of methadone—like assessing for risk factors for QTc prolongation, doing ECG screening, using low starting doses and titrating slowly, close follow-up, and considering alternative opioids—and it is important for clinicians to be knowledgeable about this medication and how to prescribe it safely before using it," he added.

The authors have disclosed no relevant financial relationships.

J Pain. 2014;15:321-337. Abstract


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