Clonazepam
Clonazepam is a long-acting benzodiazepine used in adults for selected forms of epilepsy and for panic disorder. It potentiates GABA-A signalling, with relevant dependence and cumulative sedation risks on prolonged use.
- Chemical formula
- C15H10ClN3O3
- CAS number
- 1622-61-3
- ATC code
- N03AE01
- Molecular weight
- 315.71 g/mol
- Drug class
- Benzodiazepine
- Also known as
- Ro 5-4023, Clonazepam
What is it?
Clonazepam is a 1,4-benzodiazepine first marketed in the 1970s. It was originally developed as an antiepileptic and is also used in panic disorder and selected forms of involuntary movement disorders. It is supplied as oral tablets, orally disintegrating tablets and oral solution, with parenteral preparations available in some markets. Clonazepam is dispensed only on prescription due to its potential for misuse and dependence.
Mechanism of action
Clonazepam binds the benzodiazepine site of the GABA-A receptor and allosterically enhances inhibitory chloride conductance, hyperpolarising neurons across the central nervous system. The result is anticonvulsant, anxiolytic, sedative and muscle-relaxant effects. The relatively long half-life and slow onset make clonazepam more suitable for sustained anticonvulsant action than for acute crisis management.
Pharmacokinetics
Clonazepam is well absorbed orally, with peak plasma concentrations after one to four hours and bioavailability above 80%. Plasma protein binding is approximately 85%. The drug is metabolised in the liver, mainly by CYP3A4, to mostly inactive metabolites. The terminal half-life ranges from 18 to 50 hours, supporting once or twice-daily dosing. Renal excretion of metabolites is the main elimination pathway. Hepatic impairment and CYP3A4 inhibitors increase exposure.
Indications
Clonazepam is approved in adults for the treatment of certain seizure types, including absence seizures and atypical absence seizures, myoclonic and akinetic seizures, and as adjunctive therapy in Lennox-Gastaut syndrome. It is also approved for panic disorder with or without agoraphobia. According to clinical guidelines, prescription should be limited to the lowest effective dose, with periodic reassessment, and should not be used as first-line treatment for chronic generalised anxiety disorder.
Safety profile
Common adverse effects include sedation, drowsiness, behavioural disturbances, ataxia and impaired coordination. Combination with alcohol, opioids or other CNS depressants increases the risk of severe sedation and respiratory depression. Tolerance, physical dependence and withdrawal symptoms occur with chronic use, and abrupt discontinuation can precipitate seizures. According to the prescribing information, gradual tapering is required, and concurrent use with strong CYP3A4 inhibitors needs review by the prescriber.
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Frequently asked questions
Is clonazepam used for panic attacks? ▾
Yes. Clonazepam is approved for panic disorder with or without agoraphobia in many markets, often as a short to medium-term addition to selective serotonin reuptake inhibitor therapy. According to the prescribing information, the dose is started low and titrated to clinical response, with attention to sedation. Long-term use is generally discouraged because of dependence risk and is reserved for selected cases under specialist supervision.
How does clonazepam compare with alprazolam in panic disorder? ▾
Both are benzodiazepines effective in panic disorder, but they differ in pharmacokinetics. Clonazepam has a longer half-life (18 to 50 hours), allowing once or twice-daily dosing and a more stable plasma profile, while alprazolam has a shorter half-life and requires more frequent dosing. The longer profile of clonazepam may reduce inter-dose anxiety. The choice between them is made by the prescriber based on response, tolerability and drug interactions.
Can clonazepam be stopped suddenly? ▾
No. Abrupt discontinuation after sustained use can cause withdrawal symptoms including rebound anxiety, insomnia, tremor, irritability and, importantly, seizures, even in patients without a prior seizure history. The risk increases with higher doses and longer treatment duration. According to the prescribing information, discontinuation should follow a gradual tapering schedule designed by the prescriber, often over weeks to months.
Is clonazepam safe in pregnancy? ▾
Use of clonazepam during pregnancy is generally avoided whenever possible. Benzodiazepines may be associated with neonatal withdrawal, sedation and hypotonia ("floppy infant syndrome") when used near term, and possible developmental concerns with chronic exposure. According to the prescribing information, the prescriber must weigh expected benefits against fetal risk and consider alternative treatments. Breastfeeding while on clonazepam should be discussed individually.
What are the main contraindications for clonazepam? ▾
Clonazepam is contraindicated in known hypersensitivity to benzodiazepines, in severe respiratory insufficiency, in narrow-angle glaucoma, in sleep apnoea syndrome and in severe hepatic insufficiency. Caution is required in older adults, in patients with substance use disorders and in suicidal ideation. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription.
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