The role of methadone
Findings
Methadone has often been viewed as an alternative to
oral morphine but its specifi c pharmacokinetic characteristics
and a very long and unpredictable half-life43
require careful individualisation of dosing schedules.
Oral methadone is the drug most frequently considered
as an option in the practice of opioid switching. In a
systematic review by the Cochrane Collaboration,52 which
was updated by Cherny,22 only three RCTs50,53,54 involving
277 patients addressed the comparison of methadone
with another step III opioid (one study had a third group
receiving transdermal fentanyl). The drugs did not diff er
in effi cacy between patients who were treated with step II
opioids or were opioid naive. In one study methadone
was associated with a higher incidence of sedation, which
led to a high percentage of patients dropping out because
of adverse eff ects.53 In a previous study, four (15%) of
26 versus two (8%) of 26 patients in the methadone and
diamorphine plus cocaine groups, respectively, withdrew
because of sedation.55
Although methodological limitations were found in
these three studies, data consistently show no signifi cant
diff erences in analgesic effi cacy between methadone and
morphine; the evidence of more frequent CNS sideeff
ects (sedation) with methadone is not consistent across
studies. Methadone should be considered an alternative
to other oral step III opioids.
Recommendation for use of methadone
Methadone has a complex pharmacokinetic profi le with
an unpredictably long half-life. The data permit a weak
recommendation that it can be used as a step III opioid
of fi rst or later choice for moderate to severe cancer pain.
It should be used only by experienced professionals.
Opioid switching
Findings
Opioid switching is the term given to the clinical practice
of substituting one step III opioid with another when a
satisfactory balance between pain relief and adverse
eff ects is not achieved with appropriate titration of
the fi rst opioid. This practice might be explained
pharmacologically by the phenomenon of incomplete
cross tolerance.56,57 A Cochrane review58 and an updated
systematic review23 identifi ed no randomised trial that
supports the practice of opioid switching. The available
uncontrolled trials involved 679 patients23,58 and showed
that opioid switching is done more often when pain is
not well controlled and side-eff ects limit dose escalation
than when pain is not controlled but the side-eff ects are
tolerable. The apparent success rates of switching ranges
from 40% to 80% and the most frequent switch is from
morphine, hydromorphone, or fentanyl to methadone.
Recommendation for opioid switching
The data permit a weak recommendation that patients
receiving step III opioids who do not achieve adequate
analgesia and have side-eff ects that are severe, unmanageable,
or both, might benefi t from switching to an
alternative opioid.