NIMODIPINE-ENHANCED OPIATE ANALGESIA IN CANCER-PATIENTS REQUIRING MORPHINE DOSE-ESCALATION - A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

The ability of nimodipine, a dihydropyridine calcium antagonist, to re duce the daily dose of oral morphine in cancer patients who had develo ped dose escalation, was tested in 54 patients under randomized, doubl e-blind, placebo-controlled conditions. We selected patients that requ ired at least two successive increments of morphine to maintain pain r elief. A possible pharmacokinetic interaction between nimodipine and m orphine was also studied in 14 patients by assaying steady-state serum levels of morphine and its 3- and 6-glucuronides. A total of 30 patie nts completed the study, 14 and 16 in the nimodipine and placebo group s, respectively. Nimodipine controlled the escalation of the morphine dose in 9 patients (65%), and placebo in 4 (28%), the difference bring statistically significant (P = 0.03). The dose of morphine was reduce d from 313 +/- 52 to 174 +/- 33 mg/day (P < 0.001) in the nimodipine g roup, and from 254 +/- 26 to 218 +/- 19 mg/day (not significant) in th e placebo group. The percentages of reduction in the daily dose of mor phine also showed significant differences between both groups (P = 0.0 2). One week after introducing nimodipine or placebo, while the dose o f morphine remained similar to that of the pre-test week, the serum le vels of morphine and its glucuronides were not modified significantly. We conclude that the introduction of nimodipine in patients chronical ly treated with morphine may be a safe alternative to reduce the daily requirements of the opioid. It is suggested that interference with Ca 2+-related events may attenuate the development and/or expression of t olerance to morphine in a clinically relevant way. (C) 1998 Internatio nal Association for the Study of Pain. Published by Elsevier Science B .V.