Morphine and methadone use in cancer pain

The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Editor, – Changing to methadone may be beneficial for some patients with cancer pain who are suffering the adverse effects of morphine. We are concerned that there is confusion about the dose of methadone to prescribe when making this change.

Methadone is a useful second-line analgesic for cancer pain but has its own problems. A report into methadone-related deaths in South Australia between 1984 and 1994 showed that while methadone used for drug dependence was relatively safe, this was not the case when methadone was used for pain.1 A potential danger is the view that the dose of methadone, required to produce the same analgesic effect, is identical to the dose of oral morphine.

The view that the dose ratio is 1:1 was mainly developed from single dose studies. Individual variation in the pharmacokinetics of methadone should raise concern about using this ratio when replacing morphine with methadone.2,3 Studies focusing on chronic opioid use in cancer pain have reported varying equianalgesic dose ratios. These reports suggest that:

  • the comparative pharmacology of morphine and methadone is incomplete
  • the equianalgesic dose ratio varies with the dose of morphine before the change to methadone (at higher morphine doses methadone is relatively more potent)4,5
  • for analgesia, the dose of methadone should be carefully titrated, preferably in hospital.6

We believe that there is currently no reliable morphine to methadone equianalgesic dose ratio. There is little evidence to support any protocols for starting methadone. The safest way to replace morphine with methadone is therefore by individual titration over a number of days, preferably in a hospital setting. Furthermore, we suggest that this titration should only be carried out by a clinician experienced in prescribing methadone.

If the titration takes place in hospital the patient's general practitioner must be informed of the possibility of late onset adverse effects (half-life may vary from 40 to 600 hours).

Mary Brooksbank
Director, Palliative Care
Guy Bannick
Fellow in Palliative Care
Michael Briffa
Fellow in Palliative Care
Palliative Care Unit
Royal Adelaide Hospital