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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
The overall aim of the present study is to validate the switching procedure from morphine to methadone for patients with advanced cancer and a short life expectancy. More specifically, we will:
Stein Kaasa, MD,PhD Prof.
St Olavs University Hospital, Trondheim
Norway: Norwegian Social Science Data Services