Effect of clorazepate in spasticity and rigidity: a quantitative study of reflexes and plasma concentrations

Abstract

The effect on increased myotatic reflexes of desmethyldiazepam, formed from its precursor clorazepate, was assessed in a double-blind cross-over study of 27 days duration. Eight patients with spasticity or rigidity were given placebo or active substance; first in loading doses for 2 days, then 5 mg every 12 h for a total of 10 days. A wash-out period of 7 days was interposed between the 2 10-day periods. Desmethyldiazepam had a normalizing effect on the increased phasic ankle reflexes seen in spasticity, but not on the increased tonic reflex seen in rigidity. The mean concentration of desmethyldiazepam in the steady state was 1227 nmol/l (range 600-1990 nmol/l). The plasma concentration of desmethyldiazepam tended to correlate with the percent decrease in phasic reflex activity (P = 0.08, 2-tailed). A slight drowsiness in 2 patients was the only side-effect seen. In conclusion, desmethyldiazepam given as clorazepate seems to be a suitable medicament in the treatment of spasticity.