Slow release oral morphine versus methadone: a crossover comparison of
patient outcomes and acceptability as maintenance pharmacotherapies for
opioid dependence. Mitchell TB, While JM, Somogyi AA, Bochner F. Addiction
(2004) 99: 940-945
Dear Colleagues,
This study took 18 consenting methadone maintenance (MMT) patients and
transferred their treatment to once daily, supervised slow-release oral
morphine. They then reported up to 8 weeks progress and return to
methadone. Fifteen managed the transfer without difficulty, three returning
to MMT prematurely. Reports of symptoms, side effects and preferences over
up to six weeks in the 15 were positive, about three quarters preferring the
morphine tablets, only one in five preferring the original methadone. While
this is not scientific proof of a superior treatment, it is certainly an
indication that morphine can be an acceptable alternative for most MMT
patients, with certain reported benefits in a proportion of them.
The initial conversion ratio used was 3.5:1 but every single patient
required increased doses for withdrawal symptoms, up to an average of 4.6:1
. thus, for example, a patient on 100mg of methadone might need up to 460mg
of morphine. At least two of the 11 cases (18%) returned to MMT on higher
doses (45 to 50 and 120 to 130). One of these, interestingly, was already
on the maximum dose according to the range quoted (25-120mg daily), but
evidently needed still more on medical review when returning to methadone.
The mean methadone dose in this Adelaide trial at 78mg daily is higher than
previous reports. However, it is likely that the optimal mean dose is yet
to be reached, although increases are happening slowly elsewhere (D'Aunno et
al). Until the mean dose of methadone is nearer 100mg (like Dole's very
first report) it is probable in my view that a proportion of patients will
suffer, simply by being prescribed inadequate doses. The lowest doses
overall may be in England and Victoria (Aust) where one finds poor quality
maintenance treatment along with either too much supervision (Victoria) or
too little, as in the UK. New South Wales also has many treatment
deficiencies, most glaring being a lack of treatment services in high risk
areas such as the Hunter Valley, South-western and inner Sydney. There are
also unreasonable restrictions and a lack of flexibility in some aspects of
management, especially with buprenorphine.
I understand that in NSW, morphine has been approved for over 100 patients
who have been previously registered as dependency cases. The approvals are
mostly for slow release oral morphine for 'pain management', often after
motor accidents, infections or skin grafts following overdoses. Supervision
of doses is not always compulsory. It is not usually possible to completely
separate an individual requirement for opiates for (1) dependency or (2)
analgesia purposes . and it may not matter, except for some legal aspects.
This study from Adelaide adds further evidence that a wider variety of
opioids can be safe and effective in dependency situations and the old view
of 'methadone for dependency and morphine for pain' is dated and arbitrary.
Thus we now need to find out if we can improve on 'trial and error' to
determine optimal management for our patients using methadone, buprenorphine
or alternative oral or even parenteral opioids in pharmacotherapy for
dependence.
Congratulations to Addiction for showcasing this seminal study as the lead
article for the month. Note this study followed a rigorous report by the
same authors on morphine's pharmacokinetics (see below). The first such
report I can find is from Dr Sherman in Melbourne, followed by Whitton et al
in Sydney (both 1996).
Refs: Mitchell TB, White JM, Somogyi AA, Bochner F. Comparative
pharmacodynamics and pharmacokinetics of methadone and slow-release oral
morphine for maintenance treatment of opioid dependence. Drug Alc Depend
(2003) 72;1:85-94]
Whitton G, Sunjic S, Webster I, Wickes W. Use of morphine mixture to
stabilize opiate dependence. 1996 Drug Alc Review 15: 427
Sherman JP. Managing heroin addiction with a long-acting morphine product
(Kapanol). Med J Aust 1996:165;239
Comments by Andrew Byrne ..
