Depressants Clobazam

It is interesting to note that some 1,5-benzodiazepines such as 29 also possess CNS depressant activity. Treatment of substituted diphenylamine 26 with methyl malonyl chloride and reduction with Raney nickel led to orthophenylenediamine analogue 27. Sodium alkoxide treatment led to lactam formation (28), and alkylation in the usual way with NaH and methyl iodide produced clobazam (29). °... 

Of 63 children with refractory epilepsy given add-on clobazam (mean dosage 0.8 mg/kg/day) and followed for 15-64 months, 15 (24%) had to discontinue treatment owing to adverse effects, which included severe aggressive outbursts, hyperactivity, insomnia, and depression with suicidal ideation (6). Likewise, there were behavioral or mood problems in 38 of 119 children taking clobazam... 

A 49-year-old woman, a chronic alcoholic who had been undergoing psychiatric treatment, was found dead at home (12). Autopsy findings were unremarkable. Further detailed analysis showed that the clobazam concentration found in post-mortem blood was 3.9 ig/ml higher than the usual target concentration (0.1-0.4 ig/ml). All the available information suggested that death had resulted from respiratory depression due to clobazam toxicity. 

Benzodiazepine and related hypno-sedatives increase the CNS depressant effects of alcohol to some extent. The risks of car driving and handling other potentially dangerous machinery are increased. The risk is heightened because the patient may be unaware of being affected. Some benzodiazepines used at night for sedation are still present in appreciable amounts the next day and therefore may continue to interact. Alcohol may also increase the plasma levels of brotizolam, clobazam, diazepam, and possibly triazolam, whereas alprazolam may increase blood-alcohol levels. Alcohol has been reported to increase aggression or amnesia and/or reduce the anxiolytic effects of some benzodiazepines. 

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