Clorazepate and lorazepam: clinical improvement and rebound anxiety

Abstract

Sixty-two anxious patients were treated under double-blind conditions for 4 weeks with either clorazepate or lorazepam. Two-thirds of each treatment group were then switched abruptly to placebo for 2 weeks, while one-third continued to receive active medication. Two major findings were obtained. About 70% of the patients maintained improvement during the 2-week placebo period. Some patients, however, experienced rebound anxiety, which appeared to be more intense and occurred earlier when placebo was substituted for a benzodiazepine with a short half-life (lorazepam) than for one with a long half-life (clorazepate). The clinical relevance of these findings is discussed.

Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications

“…This was confirmed by other studies [53-59]. Rebound anxiety was also observed [1, 38, 50]. It is an acute return of pretreatment anxiety above baseline following benzodiazepine withdrawal, even after short-term use.…”

“…More new withdrawal symptoms were found upon discontinuation of lorazepam (high potency and short-acting) than with diazepam [38]. Elimination rates of benzodiazepines also predict the time of onset [15] of new withdrawal symptoms: after discontinuation of rapidly eliminated benzodiazepines (i.e., lorazepam, oxazepam) [50], new withdrawal symptoms occurred within 48 h; with slowly eliminated benzodiazepine (i.e., diazepam) new withdrawal symptoms occurred after 5 days with peak severity after 9.6 days. However, 75% of patients who withdrawn after long-term use of benzodiazepines developed new withdrawal symptoms regardless of rapidly eliminated or slowly eliminated compounds [51].…”