What is the role of clonazepam in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Clonazepam, a 1,4-substituted benzodiazepine, was one of the first benzodiazepines to be used for epilepsy. It is employed in the treatment of all types of myoclonus and is useful in patients with concomitant anxiety disorder.

Clonazepam has higher affinity for the GABA-A receptor site than diazepam and binds to GABA-A receptors that do not bind with other benzodiazepines. It may have some action on sodium-channel conductance.

Clonazepam has an oral bioavailability of 80%. Tmax is 1-4 hours, but it could be delayed for as long as 8 hours. Plasma protein binding is 86% with a volume of distribution of 1.5- 4.4 L/kg. It is highly lipid soluble and can cross the blood-brain barrier rapidly. Plasma levels and antiepileptic effects are not correlated.

Clonazepam is acetylated in the liver; therefore, the metabolic rate depends on the genetic acetylator function. The metabolites of clonazepam have no clinical relevance. The drug has an elimination half-life ranging from 20 to 80 hours, and it has a very low clearance (approximately 100 mL/min in adults). Less than 0.5% is excreted in the urine.

Clonazepam levels are decreased by coadministration of enzyme-inducing drugs. No significant clinical interactions have been reported.

Clonazepam is a potent AED and the drug of choice for myoclonic seizures and subcortical myoclonus. It is also effective in generalized convulsions and, to a lesser extent, in partial epilepsies. It rarely is used as adjunctive treatment of refractory epilepsy because of its sedative effect and tolerance, which are similar to those of other benzodiazepines. It is very effective in the emergency treatment of status epilepticus, like diazepam, and can be given IV or rectally.

Withdrawal from clonazepam may induce status epilepticus or exacerbation of seizures. Psychiatric withdrawal also may occur, manifested as insomnia, anxiety, psychosis, and tremor.

Clonazepam is available as 0.5 mg, 1 mg, and 2 mg tablets and as an IV solution. The usual starting dosage is 0.25-4 mg/d once or twice daily. Slow titration is recommended.

Clonazepam’s major adverse effect is sedation, even at low doses. Children tolerate this medication much better than adults do; therefore, pediatricians use it most often. Clonazepam has the typical adverse effects of benzodiazepines (eg, ataxia, hyperactivity, restlessness, irritability, depression, cardiovascular or respiratory depression). Children and infants may have hypersalivation. Occasionally, tonic seizures may be exacerbated. Idiosyncratic reactions are rare and include marked leukopenia.

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