Nimodipine fails to enhance the analgesic effect of slow release morphine in the early phases of cancer pain treatment

We assessed nimodipine's ability to increase the analgesic effect of morphine in 32 patients suffering from cancer pain in a double-blind, placebo controlled cross-over study. Morphine administration began a few days before the start of the study. The analgesic effects of two combinations were compared: morphine (M) plus placebo (P) and morphine plus 90 mg/24 h of nimodipine (N). The study lasted 8 days, including the wash-out period, and the following sequence of treatments was applied: M + P or M + N on days 1, 2 and 3; only M on days 4 and 5; and M + N or M + P on days 6, 7 and 8. Morphine dose was individualised according to the intensity of the patient's pain and the same dose was maintained throughout the study period. Analgesic response was evaluated using four 10 cm visual analogue scales of quantitative variables for pain intensity, pain relief, sleep quality and mood. A verbal rating of qualitative variables was also scored following validated descriptors of pain in the Spanish language. No significant statistical differences were found in analgesic effect between combined treatment with nimodipine or placebo, as measured on any of the scales. In order to take into account both the short duration of treatment (8 days), and nimodipine's pharmacokinetic characteristics (half-life of 6 h and steady state of 36 h), we compared treatment with nimodipine or placebo on the third day of use, at which time, likewise, there were no statistically significant differences on any of the scales. However, when the same statistical tests were used for comparison of results with pre-treatment baseline values, highly significant differences between mean scores on the scales for pain relief and pain intensity were found. Based on these negative results we conclude that nimodipine given orally at a dose of 30 mg every 8 h does not enhance analgesia when associated with morphine in the early phases of treatment for cancer pain. Our study also gives clear evidence of a placebo effect.