Efficacy and safety of pregabalin in patients with neuropathic cancer pain undergoing morphine therapy.

Aim: To evaluate the efficacy and the safety of pregabalin (PGB)-morphine combination for the treatment of neuropathic cancer pain (NCP). Methods: In this double-blind, randomized, placebo (PL)-controlled crossover study, 40 cancer patients with severe NCP were randomized into two groups (20 per group): PGB-PL and PL-PGB. Patients in the PGB-PL group received PGB plus oral morphine in phase I, and PL plus oral morphine in phase II. The treatment sequence for the PL-PGB group was PL plus oral morphine in phase I, and PGB plus oral morphine in phase II. These 2-week treatment periods were separated by a 1-week washout period. The primary outcome measure was the decrements in morphine dose; secondary outcomes included quantitative assessments of sleep (rated according to the Medical Outcomes Study Sleep Scale), the Constipation Assessment Scale and adverse effects. Results: The mean minimal effective dose of morphine was 184.4 +/- 69.9 mg/day in the period of PGB treatments, which was significantly lower than that of PL-controls (228.7 +/- 66.9 mg/day; P < 0.001) and baseline (247.5 +/- 80.0 mg/day; P < 0.001). Compared with PL, PGB resulted in a significant sleep improvement as measured by sleep disturbance, sleep quantity, and sleep problems index (P < 0.001), as well as a Constipation Assessment Scale reduction (P < 0.001). PGB resulted in a higher frequency of dry mouth and somnolence than PL (P < 0.05). Conclusion: PGB enhances the efficacy of oral morphine and reduces dose-related adverse reactions. The PGB-morphine combination is an effective approach to controlling NCP.