Double Bedtime Dosing During Immediate-Release Morphine Administration to Cancer Patients: A Randomized, Double-Blind Cross-Over Comparison of a Double Bedtime Dose Ver-Sus Two Standard Doses at Bedtime and at Night
Double bedtime dosing during immediate-release morphine administration to cancer patients:
A randomized, double-blind cross-over comparison of a double bedtime dose versus two
standard doses at bedtime and at night
Oral morphine is recommended by the World Health Organization for pain control in moderate
or strong cancer pain 1. At our hospital we use the practice recommended by the Expert
Working Group of the European Association for Palliative Care for introduction of strong
opioids with titration with immediate-release (IR) morphine dosed every 4 hour until an
optimal balance between analgesia and side effects is achieved. After the optimal daily dose
is defined slow-release (SR) morphine in the same total daily morphine dose is started 2.
One of the features of the EPAC guidelines is that patients during treatment with IR
morphine are given a double bed-time that replaces the next 4-hourly dose during night 2.
The rationale behind this recommendation is that giving a double dose will prolong duration
of morphine analgesia and eliminate the need for awaking the patient during night. However,
this recommendation is based on expert opinion and not evidence from clinical studies 2.
Todd et al. has recently presented results that challenge this approach from a cross-over
study in which the patients received either a double bedtime dose or regular doses every
4-hour 3. This study showed that patients receiving a double bedtime dose reported more
pain, more use of rescue medications and reported inferior sleep quality compared to
patients receiving regularly scheduled doses. A limitation of this study was that they did
not perform the study blinded and thus consequently the results are subject to bias. It is a
need for a placebo-controlled study before the evidence carries enough weight to change
Besides a clinical study it is also relevant to obtain pharmacokinetic observations during
double bedtime and regularly IR morphine dosing. Repeated blood sampling will disturb the
patients during night and hence confound the clinical observations (e.g. sleep quality).
Consequently, the blood samples will not be obtained in the same dosing interval where the
clinical data are obtained.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary efficacy variable
Paal Klepstad, Md,PhD
St.Olavs University Hospital, Norway
Norway: Norwegian Social Science Data Services