Metabolic and subjective responses to oral diazepam and midazolam

Diazepam premedication decreases the overall metabolic rate and oxygen consumption. Whether its properties are shared by midazolam is not known. In this study, eight healthy male volunteers were given oral diazepam (10 mg), midazolam (15 mg) and placebo in a random double-blind cross-over fashion. Metabolic responses were measured using an indirect calorimetry device. Subjective responses were measured using a visual analogue scale. Plasma concentrations of diazepam, midazolam and desmethyldiazepam were analysed and correlated to changes in metabolic and subjective responses. When compared to placebo, both diazepam and midazolam significantly decreased oxygen consumption (P < 0.01 in pairwise comparisons) and energy expenditure (P < 0.01 in pairwise comparisons). While there was a significant correlation between the plasma concentrations of diazepam and the changes in metabolic parameters, no such correlation was found with midazolam. Both diazepam and midazolam were subjectively more sedative than placebo (P < 0.05). There was no significant difference between the sedative effects of diazepam and midazolam, but diazepam was subjectively better tolerated than midazolam. These results indicate that both diazepam and midazolam, in addition to their CNS effects, significantly decrease the overall metabolic rate and oxygen consumption in healthy volunteers.