Clorazepate.

Dependence, tolerance and withdrawal define the risk profile. In a dog model, 36 hours after stopping five to six weeks of clorazepate dosing, the convulsive threshold fell below baseline in every animal, a clear sign of physical dependence ^[11]. Rebound anxiety on abrupt discontinuation occurs later and less intensely than with the short acting lorazepam, but it still appears in a subset of patients ^[5]. The most common adverse effects in the 336 patient buspirone comparison were drowsiness and depressed mood, both significantly more frequent with clorazepate, and drug related adverse events were more likely to interfere with treatment than with buspirone ^[4]. Psychomotor and memory impairment, falls in the elderly and next day sedation follow from the long lived metabolite; in a double blind crossover in partial seizure patients, the clorazepate plus phenytoin regimen matched phenobarbital plus phenytoin for seizure control with significantly less objective and subjective toxicity ^[9]. Alcohol and opioids are contraindicated combinations; clorazepate remains a standard tool in managed alcohol withdrawal, where a 226 patient series reported no withdrawal convulsions during five day prophylaxis ^[6], and intravenous clorazepate proved an alternative to clomethiazole in severe delirium tremens, with a lower heart rate and fewer cardiopulmonary complications ^[7]. A single case report described jaundice with hepatic necrosis attributed to potassium clorazepate, with the authors advising against use in suspected hepatic dysfunction ^[14]. In a rat teratology study, intramuscular clorazepate during organogenesis produced no increase in malformations or fetal wastage ^[12]; human pregnancy data are limited and benzodiazepine use in pregnancy is generally discouraged. In a laboratory aggression paradigm, clorazepate 15 mg did not increase aggressive responding, unlike diazepam 10 mg ^[13]. A 2023 randomized phase II trial compared clomethiazole with clorazepate during alcohol detoxification for effects on hepatic fat and serum transaminases in alcohol associated liver disease ^[15]. This is research information, not medical advice.

Clorazepate was developed by Abbott Laboratories and introduced in the United States in 1972 as Tranxene, among the first benzodiazepines marketed explicitly as an anxiolytic prodrug. The name clorazepate refers to the acid; clinical products use the dipotassium salt. Its metabolic trick, gastric decarboxylation to nordazepam, made it a forerunner of prodrug thinking in the class and was characterized in the 1970s and 1980s.

A respected older anxiolytic, the calm long acting alternative in the benzodiazepine family, still widely used in France as Tranxilium and in other markets, and a standard component of alcohol detoxification protocols. Its dependence potential keeps it tightly controlled, and modern prescribing has moved toward shorter acting options, so its reputation is that of a solid, dated workhorse.