Is disease progression the major factor in morphine 'tolerance' in cancer pain treatment?

To assess the contribution of pharmacological tolerance to increasing doses of morphine, 29 cancer patients requiring oral morphine to treat pain were studied by two teams working independently. The first team assessed physical impairment, pain intensity and pain treatment. The second team assessed depressive disorders (DSM III criteria), emotional and behavioural depressive patterns (Retardation Depressive Scale, Polydimensional Mood Scale). All patients were seen at the initiation of morphine therapy and followed to the first morphine dose modification. Evaluations were carried out in out-patient clinics except staging investigations which were undertaken at the beginning and at the end of the study. Our results showed that (1) in 24 of the 25 patients for whom morphine doses were increased, progressive disease was recorded; (2) in 4 patients, morphine doses were not increased and in these patients their disease was stable or in remission; and (3) changes in depressed mood were not correlated with pain intensity. These data strongly suggest that, instead of pharmacological tolerance, the main factor resulting in increasing oral morphine requirement in cancer pain management is pain increase due to disease progression.