Improved physician education and patient counseling about methadone safety and ECG monitoring to identify patients at high risk for cardiac problems will lead to safer use of the medication, according to the American Pain Society's Clinical Practice Guideline on Methadone Safety, published this week in The Journal of Pain.
Methadone is a synthetic opioid narcotic to treat opioid addiction and chronic pain. Safety of the drug has been a major clinical concern in recent years. U.S. deaths from methadone overdoses have increased from 800 in 1999 to 4,900 in 2008. The increase in mortality has been substantially higher than for any other opioid medication, and is attributed to a sharp rise in prescribing methadone for chronic pain.
Previous methadone guidelines covered prevention of cardiac arrhythmias caused by methadone. These guidelines did not address methadone safety issues aside from cardiovascular risks.
In preparing the new methadone safety guideline, the APS expert panel reviewed more than 3,700 scientific abstracts. Under the direction of the Oregon Evidence-based Practice Center, the group reviewed evidence assessing a variety of topics related to methadone safety.
"The intent of the guideline is to provide evidence-based recommendations for use of methadone in persons of all ages for treatment of chronic pain in primary care or specialty settings, or for use in licensed opioid addiction treatment programs," said Roger Chou, M.D., lead author and head of the APS Clinical Practice Guideline Program. "The guideline is based on a systematic review of the evidence on methadone safety, and the panel concluded that measures can be taken to promote safer use. Safely prescribing this medication requires clinical skill and knowledge to mitigate risks related to overdose and cardiac arrhythmias."
Chou added that recommendations in the guideline were rated as strong or weak. Strong recommendations were based on the panel's assessment that potential benefits outweigh harms or burdens or that potential harms clearly outweigh benefits.
Key recommendations are:
Patient Assessment: Careful patient selection for methadone is essential and should be based on a thorough history, review of medical records and physical examination. Assessment results can be used to stratify patients based on 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.
Education and Counseling: Clinicians should counsel patients about potential risks and benefits prior to beginning methadone therapy. Patients should be advised to take methadone as prescribed and comply with recommended follow up and monitoring. Caregivers should be notified about risks for respiratory depression and authorized to withhold additional doses of methadone and contact the prescriber if signs of respiratory depression or somnolence occur.
Baseline Electrocardiograms: ECG exams should be performed prior to initiating methadone therapy. The test will help clinicians assess risks for arrhythmias. Methadone is associated with risk for prolonged QTc intervals, which measure electrical polarization and depolarization of heart ventricles. Lengthened QTC interval is a diagnostic marker for arrhythmias and possible sudden death. Recent data suggest that methadone is the most common drug-related cause of ventricular arrhythmia.
Alternative Medications: The panel recommended that clinicians consider buprenorphine as an option for patients being treated for opioid addiction who have risk factors for prolonged QTc intervals.
Low Beginning Dose: Methadone treatment should be started at low doses (no more than 30-40 mg daily) and titrated 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 of unintended drug accumulation and accidental overdose.
Urine Drug Testing: Urine drug testing should be performed before initiating methadone therapy and at regular intervals for patients treated for opioid addiction.