Q & A About Methadone
By Lynn R. Webster, MD, FACPM, FASAM
Medical Director, Lifetree
Medical Director and CEO, Lifetree Clinical Research,
Salt Lake City, Utah
Q. What are methadone's benefits and potential dangers?
Research demonstrates that methadone can be effective in
treating some forms of neuropathic pain but also requires
specific knowledge to use safely. Several states have recorded
increases in accidental overdose deaths, many of them involving
methadone. More research is needed into the exact reasons
for the deaths, but at last some contribution appears to be
tied to methadone prescribed for pain. There is difficulty
in analyzing methadone's distinct contribution because lethal
blood levels may vary depending on the decedent's degree of
opioid tolerance, the severity of chronic pain and the action
of polydrug combinations. Levels of methadone typically reported
as a cause of death may actually be therapeutic in some chronic
pain patients on long-term methadone therapy. Regardless,
methadone does present some unique pharmacologic properties
that need to be understood to utilize it safely.
Q. What should a clinician know about methadone before
prescribing it for pain?
Pain experts typically administer opioids in the belief that
patients quickly develop near complete tolerance to respiratory
depression. Research is beginning to indicate that clinicians
may underestimate the risk of respiratory depression, particularly
in the initial conversion to methadone. Methadone is eliminated
from the body at a slower rate than many other opioids. Its
long, variable half-life averages around 48 hours but can
be up to 100 hours. Methadone's properties increase its potential
for polydrug interactions. Also, if patients defy medical
direction and escalate methadone doses in an attempt to control
their pain, the results can be lethal.
Q. What is methadone's relationship to sleep?
Methadone-related deaths may be influenced by a patient's
dosing schedule, including time of the last dose of the day
in relation to the onset of sleep. In particular, the presence
of sleep apnea appears to pose a risk: New research suggests
a relationship between doses of methadone and increased incidence
of sleep apnea, particularly in combination with benzodiazepines.
If patients are at risk for sleep apnea, clinicians are advised
to obtain a sleep study to determine whether patients require
supplemental oxygen, continuous positive airway pressure (CPAP)
or some other support to safely consume methadone for pain.
Q. What is the safe approach to an initial dose of methadone?
Clinicians are advised to start methadone therapy with a
low dose and titrate slowly to an analgesic effect. Published
conversion tables are inadequate in giving equianalgesic doses
of methadone compared to other opioids. Cross tolerance from
other opioids to methadone is incomplete, and the tables are
designed for a single dose, not for chronic administration.
The result may be a recommended starting dose that is too
For now, safe practice supports starting methadone with a
ceiling dose of no more than 20 mg/day (10 mg/day for elderly
or infirm patients). Dose changes should not occur more often
than weekly to allow a steady state of methadone to develop
and for the peak side effects to become clear. For patients
who are being converted from another opioid to methadone,
clinicians should slowly titrate downward the other opioid
as they slowly titrate methadone upward. This practice will
minimize the risk of withdrawal and the risk of overdose involving
either methadone or a combination of the two opioids.
These guidelines represent a more conservative recommendation
than seen elsewhere. Certainly, some patients are able to
tolerate a much more rapid conversion or titration. Nevertheless,
given the reports of deaths associated with methadone, these
starting guidelines should help clinicians ensure patient
safety and give methadone pain therapy a greater chance of
Q. How should patients be counseled?
Patient counseling must include an emphasis on following
all medical instructions to the letter: no escalation of doses
and no mixing of methadone with other prescriptions, alcohol
or illicit substances. Patients should be warned that any
deviation in this regard can be dangerous, even fatal.
Patients should be apprised of the danger of taking anyone
else's prescriptions and of the need to lock up all prescription
opioids to prevent them being stolen or consumed by others.
Center for Substance Abuse Treatment, Methadone-Associated
Mortality: Report of a National Assessment, May 8-9, 2003.
CSAT Publication No. 28-03. Rockville, MD: Center for Substance
Abuse Treatment, Substance Abuse and Mental Health Services
Administration, 2004. Available here.
Webster LR. Methadone-related deaths. J Opioid
Webster, LR, Fakata, K. Sleep Apnea Associated with Methadone
and Benzodiazepine Therapy Presented at the American Academy
of Pain Medicine 22nd Annual Meeting, February 22-25, 2006,
San Diego, CA. Poster 165.
Updated October 9, 2006