Clonazepam

• Seizure Disorders
• Panic Disorder
• Lennox-Gastaut Syndrome
• Myoclonic Seizures

Clonazepam is a benzodiazepine medication used primarily for the treatment of seizure disorders and panic disorder. This long-acting benzodiazepine provides effective control of various seizure types and offers anxiolytic properties for panic attacks, though its use requires careful consideration of dependence and withdrawal risks.

Mechanism of Action

Clonazepam enhances the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor. By binding to a specific site on the GABA-A receptor complex (distinct from the GABA binding site), clonazepam increases the frequency of chloride channel opening when GABA binds, leading to increased neuronal inhibition. This results in anticonvulsant, anxiolytic, muscle relaxant, and sedative effects. Clonazepam has particularly potent anticonvulsant activity, making it useful for multiple seizure types including absence seizures, myoclonic seizures, and akinetic seizures. Its long half-life (30-40 hours) provides sustained therapeutic effects.

Available Formulations

Clonazepam is available as oral tablets (0.5 mg, 1 mg, 2 mg) and orally disintegrating tablets (0.125 mg, 0.25 mg, 0.5 mg, 1 mg, 2 mg). The orally disintegrating tablets dissolve on the tongue without water. Clonazepam is a Schedule IV controlled substance due to its potential for abuse and dependence. Generic formulations are widely available.

Medical Uses

Clonazepam is FDA-approved for the treatment of Lennox-Gastaut syndrome (petit mal variant), akinetic seizures, myoclonic seizures, absence seizures (when succinimides fail), and panic disorder with or without agoraphobia. Off-label uses include other anxiety disorders, restless legs syndrome, REM sleep behavior disorder, acute mania, tardive dyskinesia, and essential tremor. It is often used as adjunctive therapy in complex seizure disorders.

Dosing Guidelines

For seizure disorders in adults, treatment typically starts at 0.5 mg three times daily, increasing by 0.5-1 mg every 3 days until seizures are controlled or side effects occur. Maintenance doses range from 1-20 mg daily in divided doses. For panic disorder, the starting dose is 0.25 mg twice daily, increasing to a target of 1 mg daily after 3 days. Maximum dose for panic is 4 mg daily. Pediatric dosing is weight-based: 0.01-0.03 mg/kg/day initially, not exceeding 0.05 mg/kg/day in divided doses. Elderly patients should start at lower doses.

Important Safety Information

Clonazepam carries a boxed warning regarding concomitant use with opioids, which can result in profound sedation, respiratory depression, coma, and death. The medication has significant potential for dependence and withdrawal; abrupt discontinuation can cause seizures even in patients taking it for non-seizure indications. Withdrawal should be gradual (0.125 mg twice daily reduction every 3 days). Paradoxical reactions (increased anxiety, aggression) may occur. Use is contraindicated in acute narrow-angle glaucoma and significant liver disease.

Drug Interactions

Concurrent use with opioids, alcohol, or other CNS depressants increases sedation and respiratory depression risk. CYP3A4 inhibitors (ketoconazole, fluvoxamine) can increase clonazepam levels. CYP3A4 inducers (phenytoin, carbamazepine, rifampin) can decrease levels. Clonazepam may increase phenytoin levels. Caution is needed with other psychotropic medications. Alcohol should be avoided.

Special Populations

Clonazepam is associated with an increased risk of congenital malformations when used during the first trimester (Category D). Use during late pregnancy may cause neonatal withdrawal or floppy infant syndrome. It is excreted in breast milk; breastfeeding is not recommended. Safety and efficacy have been established in pediatric patients for seizure disorders but not for panic disorder. Elderly patients are more sensitive to benzodiazepines and should use lower doses. Dose reduction is recommended in hepatic impairment; use is contraindicated in severe hepatic disease.