Switching From Morphine to Methadone. A Clinical, Pharmacological and Pharmacogenetic Study

This study is based on the clinical observation that patients who are not well controlled on morphine or oxycodone may benefit from switching to another opioid, in this case methadone. Although the mechanism for such switch is not completely understood, evidence indicates that opioids with different chemical structures have different characteristics, not least in relation to new knowledge about genetic variation in opioid receptors. Another challenge is that there is much uncertainty regarding equianalgesic dose ratios for morphine and methadone. It seems that the higher the morphine doses, the relatively lower methadone doses are needed to substitute morphine. Furthermore, there is uncertainty to which switching procedures one should use, the most common ones are "stop and go" and a three days switch. Finally, it is reported that methadone may increase the QT interval of the ECG, and thus increase the risk for the ventricular arrhythmia Torsade de pointe. The aim of this randomized, open label, multicenter study is primarily to compare the switching procedures, but it will also provide more knowledge about equianalgesic dose ratios, the effect of methadone on the QT interval, genetical factors that may characterize patients needing opioid switch as well as their response to it, and finally if pharmacokinetic factors plays a role.

Inclusion criteria

• • Malignant disease.

• On morphine and in need of opioid rotation. (A patient in need of opioid rotation is defined as having insufficient pain control with or without unacceptable side effects from opioids).
• Able to complete the planned assessment schedules.
• Above 18 years of age.
• If out-patient, the patient lives with someone who can observe him/her.
• Given informed consent according to the ethical guidelines.

Exclusion criteria

• Not able to read or write in Norwegian
• The patient has participated in a clinical study 4 weeks prior to inclusion