Clomethiazole (chlormethiazole)

Nervous system

In a double-blind, double-dummy, placebo-controlled comparison of clomethiazole and gammahydroxybutyrate in ameliorating the symptoms of alcohol withdrawal, alcohol-dependent patients were randomized to receive either clomethiazole 1000 mg or gammahydroxybutyrate 50 mg/kg [ ]. There was no difference between the three treatments in ratings of alcohol withdrawal symptoms or requests for additional medication. After tapering the active medication, there was no increase in withdrawal symptoms, suggesting that physical tolerance did not develop to either clomethiazole or gammahydroxybutyrate during the 5-day treatment period. The most frequently reported adverse effect of gammahydroxybutyrate was transient vertigo, particularly after the evening double dose.

The effect of clomethiazole on cerebral outcome in patients undergoing coronary artery bypass surgery has been investigated in 245 patients, who were randomized double-blind to placebo or clomethiazole (1800 mg over 45 minutes followed by 800 mg/hour until the end of surgery) [ ]. A battery of eight neuropsychological tests was administered preoperatively and repeated 4–7 weeks after surgery. There were no differences between the clomethiazole and placebo groups in postoperative neuropsychological tests scores. Thus, clomethiazole did not improve or worsen cerebral outcome after coronary artery bypass surgery.

The efficacy and safety of clomethiazole (75 mg/kg by intravenous infusion over 24 hours), as a neuroprotective drug, were studied in a double-blind, placebo-controlled trial (CLASS, the Clomethiazole Acute Stroke Study) in 1360 patients with acute hemispheric stroke [ ]. Clomethiazole was generally well tolerated and safe. Sedation was the most common adverse event, leading to treatment withdrawal in 16% of patients compared with 4.2% of placebo-treated patients.

In a small subset of CLASS (95 patients) mortality at 90 days was 19% in the clomethiazole group and 23% in the placebo group [ ]. Sedation was the most common adverse event (clomethiazole 53%, placebo 17%), followed by rhinitis and coughing. The incidence and pattern of serious adverse events was similar between the groups.

A report has illustrated the dangers of driving a motor vehicle whilst taking clomethiazole [ ].

• A 53-year-old male car driver was followed by the police for about 2 km, while he drove in an unsafe manner, until the car crashed into the owner’s garage. Analysis of his blood showed a clomethiazole concentration of 3.3 μg/ml. Neither alcohol nor any other drug could be detected. One day later he committed suicide by swallowing at least 60 capsules of clomethiazole.