Tolerance and Dependence
Tolerance may occur to quazepam but more slowly than seen with other benzodiazepines such as triazolam. However, quazepam causes significantly less drug tolerance and less withdrawal symptoms including less rebound insomnia upon discontinuation compared to other benzodiazepines. Quazepam may cause less rebound effects than other type1 benzodiazepine receptor selective nonbenzodiazepine drugs due to its longer half-life. Short acting hypnotics often cause next day rebound anxiety. Quazepam due to its pharmacological profile does not cause next day rebound withdrawal effects during treatment.
No firm conclusions can be drawn however, whether long term use of quazepam does not produce tolerance as few if any long term clinical trials extending beyond 4 weeks of chronic use have been conducted. Quazepam should be withdrawn gradually if used beyond 4 weeks of use to avoid the risk of a severe benzodiazepine withdrawal syndrome developing. Very high dosage administration over prolonged periods of time, up to 52 weeks, of quazepam in animal studies provoked severe withdrawal symptoms upon abrupt discontinuation, including excitability, hyperactivity, convulsions and the death of two of the monkeys due to withdrawal related convulsions. More monkeys died however, in the diazepam treated monkeys. In addition it has now been documented in the medical literature that one of the major metabolites of quazepam, N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), which is long acting and prone to accumulation, binds unselectively to benzodiazepine receptors, thus quazepam may not differ all that much pharmacologically from other benzodiazepines.
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