Comparison of two benzodiazepines with differing accumulation: behavioral changes during and after 3 weeks of dosing

The effects of diazepam (0.2 mg/kg for 15 days followed by 0.3 mg/kg for 7 days), oxazepam (0.8 mg/kg for 15 days followed by 1.2 mg/kg for 7 days), and placebo were studied in healthy subjects after the first dose, once a week during chronic dosing, and at 48 and 96 hours after withdrawal through a battery of psychologic tests. Diazepam produced quick effects followed by relatively rapid recovery, whereas the effects of oxazepam appeared slowly and lasted longer. Tolerance developed to the effects of both active drugs, so that when the dosages were increased, effects did not. There were no symptoms or signs indicative of withdrawal reactions. There were also no differences between the effects of the two active drugs after repeated dosing, although diazepam is an accumulating drug with active metabolites and oxazepam is a slightly accumulating one with inactive metabolites.