Analgesic effects of lamotrigine and phenytoin on cold-induced pain: a crossover placebo-controlled study in healthy volunteers

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The analgesic activity of a single dose of lamotrigine (300 mg p.o.) and phenytoin (300 mg p.o.) was evaluated in a randomised, double-blind, placebo-controlled study in 12 healthy volunteers. A computerised cold-pressor test (CPT) was used to measure analgesia. Dihydrocodeine (90 mg p.o.) was used to validate the effectiveness of the CPT in measuring analgesia in the volunteers. On each study day the volunteers performed the CPT before study medication and at 1.25, 2.75, 4.25 and 5.75 h post-dose. Psychomotor tests were carried out before each CPT to determine possible drug-induced sedation. These included digit symbol substitution, critical flicker fusion and choice reaction time. Subjective feelings of concentration, vigilance and relaxation were also measured using visual analogue scales. All three active drugs significantly reduced pain scores. Maximum pain relief was achieved at 1.25 h post-dose for both dihydrocodeine and lamotrigine, whereas for phenytoin it occurred at 4.25 h post-dose. There was a significant association between analgesia and plasma concentrations of lamotrigine (P=0.013) and phenytoin (P=0.028). There were no significant differences in the sedation produced by any of the active drugs, compared to placebo. The findings of this study suggest that lamotrigine and phenytoin could have a wider clinical use as analgesics.

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