Effect of Dose Escalation Pace on Benzodiazepine Clinical Response

Hsu and Laddu (1) have shown that the rate of dose escalation needs to be considered when reviewing adverse event occurrence. The data of a Phase III flexible-dose clinical trial with a titration design were retrospectively examined to assess the effect of dose escalation on benzodiazepine efficacy performance in the treatment of patients with panic disorder. Most of the patients in the low dose group have a slow escalation and therefore, the high dose group was the focus. It was observed that fast dose escalation (an average daily dose increment of more than three tablets) makes benzodiazepine less efficacious. In other words, benzodiazepine-treated patients with fast dose escalation are less likely to respond in a diminishing number of panic attacks. Contrary to patients on benzodiazepine, more patients under placebo with a fast dose escalation pace responded. Similar analysis on medical events, symptoms of disease, or adverse events also showed the same pattern. The logistic regression analysis on the response status and analysis of variance on the medical event improvement scores with dose increment as an additional factor in the model confirmed the effect of dose escalation pace.