2 August 2004

Slow release oral morphine versus methadone

Addiction (2004) 99: 940-945



A crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence. Mitchell TB, While JM, Somogyi AA, Bochner F.



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 ..