Expert opinion from ASAM stresses safety during MMT start-up
For roughly half a century, methadone dispensed in federally certified opioid treatment programs (OTPs) in the United States has been a well-studied, effective, and relatively safe addiction therapy. Yet, there have been ongoing incidents of methadone-associated overdoses and deaths, largely due to its widespread prescription and frequent misuse as a pain reliever, but also to a lesser extent in patients attending OTPs.
When properly prescribed and used in OTPs, methadone has a favorable safety profile; however, there can be special risks of overdose and death from methadone during start up and early phases of treatment. To address these concerns, the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) invited the American Society of Addiction Medicine (ASAM) to convene an expert panel to develop a consensus statement on methadone induction and stabilization, which provides recommendations for reducing risks of overdose or death related to the methadone maintenance treatment (MMT) of addiction.
Methadone Start-Up Takes Time and Caution
A distinguished panel of 10 experts in the MMT field—the “Methadone Action Group,” including Drs. Louis Baxter, Anthony Campbell, Michael DeShields, Petros Levounis, Judith Martin, Laura McNicholas, Tom Payte, Ed Salsitz, and Trusandra Taylor, along with Bonnie Wilford, MS—conducted a comprehensive literature search spanning 1979-2011. The group evaluated the resulting information and collaborated in formulating a best practices consensus document, which was subsequently reviewed and commented on by more than 100 experts in the addiction treatment field.
The final document, published in the November/December edition of ASAM’s Journal of Addiction Medicine [Baxter et al. 2013; PDF here], extensively focuses on safety during the 3 most critical phases of starting MMT: A. methadone induction (weeks 1-2); B. early stabilization (weeks 3-4); C. late stabilization (weeks 5+).
According to the medical literature examined by the expert panel, overdoses and deaths during methadone induction most commonly may occur either because 1) the initial dose is too high, 2) the dose is increased too rapidly, or 3) the prescribed methadone interacts with another drug. Therefore, the panel developed recommendations that help methadone providers avoid or minimize these risks.
When it comes to the initial methadone dosing at MMT start-up, the panel stresses the traditional advice to “start low, go slow.” Acknowledging the difficulties of accurately assessing a new patient’s opioid tolerance—and, therefore, a definitely “safe” methadone dose—the initial dose of methadone should typically range between 10 mg to 30 mg per day. An additional 5-10 mg/day is allowed if necessary to help relieve persistent withdrawal symptoms; however, the standard in the U.S. is that the total daily dose should not exceed 40 mg.
There are a number of high-risk situations to consider that may prompt low initial dosing. These include patient age >60 years, recent use of sedating drugs (e.g., benzodiazepines), alcohol abuse or dependence, concurrent physical disorders (e.g., respiratory or cardiac disease, sleep apnea, central nervous system depression, and others), or taking medications that either increase or decrease methadone metabolism.
It is essential to medically assess patients at intake and closely monitor their response to therapy. It may take several weeks before an optimal methadone dose can be safely achieved, during which time symptoms of withdrawal may persist to some degree, especially late in the day or during the night.
The ASAM panel states that the first day’s methadone dose may be increased “every five or more days in increments of 5 mg or less” [note that this dose increase is at the low end of what previous guidance has recommended]. Because methadone levels accumulate gradually before reaching a steady state, whereby opioid withdrawal is prevented throughout a 24-hour period, patients should be carefully assessed and they often need more time for full effects to be realized rather than more daily methadone during the induction period.
The first 2 weeks of MMT are a critical period from a safety standpoint, and the ASAM expert panel discusses the many subtle factors that may influence a patient’s therapeutic response to methadone and also affect clinical impressions of overmedication. For example, individual patient differences in metabolism may alter the duration of methadone effects; furthermore, in some cases, overmedication may be marked by unexpected feelings of excess energy, with or without euphoria.
Beyond the first 2 weeks—during early and late stabilization—the objective is to achieve a methadone maintenance dose allowing the patient to live a better life free of withdrawal symptoms, drug intoxication or excessive sedation, or troublesome drug craving. Various factors may upset this process—e.g., changes in physical health, psychological distress, continued substance abuse, etc.—so ongoing patient assessments and methadone dose adjustments may be necessary in some cases for an extended period of time. The ASAM expert panel does not comment on what optimal methadone dosing eventually might be, other than to note that “some patients require doses larger than 120 mg/day” for blocking euphoric effects of self-administered (e.g., illicit) opioids.
This new evidence-based document from ASAM is the first time all of this vital information has been so extensively brought together in one place; so, it is recommended and important reading for all persons involved or interested in MMT. At the same time, the principles and best practices described are not entirely new; indeed, this topic was previously discussed, although more briefly, in past AT Forum articles [see Special Report 2003 and ATF fall 2006]. Additionally, in 2007, a methadone induction instruction handout for patients and significant others was made available to AT Forum readers by Tom Payte, MD (who also is one of the Methadone Action Group panel members) [PDF here].
Education and Preparedness Are Essential
Methadone overdose can have a deceptive and slow onset, and the ASAM panel stresses the importance of patient and family education beginning with intake into MMT. Involvement of family [or significant others, and presumably with patient consent] can be a critical safety measure by helping to ensure that they understand the lengthy process of methadone induction and stabilization, as well as the signs/symptoms of overmedication and overdose to watch for along the way. Being able to recognize therapeutic risks and potential problems, and knowing appropriate actions to take if problems do occur, are essential for OTP staff, patients, and patients’ families.
Unfortunately, in the ASAM document there is only a single mention of naloxone, which is an effective and safe antidote for methadone overdose. It states, “Opioid treatment programs should establish protocols for emergency response to and management of patient overdoses, including onsite availability of naloxone and any necessary support and education for families.”
Indeed, there appears to be growing interest in the U.S. (and in other countries) in making naloxone more widely available to patients, their families, and others for helping to reverse opioid overdose in an emergency—whether involving prescribed or illicit opioid agents. For example, Washington State has an aggressive program of naloxone distribution [see StopOverdose.org] and the ASAM expert panel references an “Opioid Overdose Prevention Toolkit” from SAMHSA [PDF here] that discusses how to identify overdose and the use of lifesaving naloxone. Methadone overdose in MMT—what to know; how to prevent it; what to do if it happens (including naloxone) —was the theme of a past edition of AT Forum [Summer 2007 PDF].
In sum, careful management of methadone induction and stabilization, coupled with patient/family education and increased clinical vigilance by staff, can be lifesaving measures during MMT. According to Louis Baxter, MD—ASAM immediate Past-President and chair of the expert panel—in a press release [PDF here], “The use of methadone to treat addiction has saved countless lives in the last 50 years, but it also has an increased risk of toxicity and adverse events for the patient during the medication’s induction and stabilization phases. The protocols designed by the ASAM expert panel could dramatically decrease these negative outcomes if all clinicians prescribing methadone would follow them.”
Baxter LE, Campbell A, DeShields M, Levounis P, Martin JA, McNicholas L, Payte JT, Salsitz EA, Taylor T, Wilford BB. Safe Methadone Induction and Stabilization: Report of an Expert Panel. J Addiction Med. 2013(Nov/Dec);7(6):377-386. PDF available at: http://www.asam.org/advocacy/find-a-policy-statement/view-policy-statement/public-policy-statements/2013/11/26/safe-methadone-induction-and-stabilization. Access checked 1/29/2014.
Leavitt SB. Methadone Dosing & Safety. AT Forum [special report]. 2003 (September). PDF available at: https://atforum.com/documents/DosingandSafetyWP.pdf. Accessed 1/27/2014.
Methadone Overdose in MMT. AT Forum. 2007(Summer);16(3). PDF available at: https://atforum.com/pdf/Summer07_news.pdf. Access checked 1/29/2014.
Payte JT. Methadone induction instructions to patients and significant others. CMG Induction Handout v7; 2007. PDF available at: https://atforum.com/pdf/PayteSafetyInstructions.pdf. Accessed 1/29/2014.
Safely starting methadone in MMT. AT Forum. 2006(Fall);15(4). PDF available at: https://atforum.com/documents/2006Fall.pdf Accessed 1/27/2014.
SAMHSA (Substance Abuse and Mental Health Services Administration). Opioid Overdose Prevention Toolkit. Rockville, MD: HHS Publication No. (SMA) 13-4742; 2013. PDF available at: http://store.samhsa.gov/shin/content//SMA13-4742/Overdose_Toolkit_2014_Jan.pdf. Access checked 1/29/2014.
StopOverdose.org. University of Washington Alcohol & Drug Abuse Institute. 2013. Website at: http://www.stopoverdose.org/pharmacy.htm. Access checked 1/29/2014.
Stewart B. Leavitt, MA, PhD, is a former editor of Addiction Treatment Forum and most recently was director/editor of Pain Treatment Topics.