1,5-benzodiazepine antiepileptic
ATC code: N05BA09 (Clobazam)
Brand names
Onfi, Frisium, Sympazan
A 1,5-benzodiazepine – a structural variant with nitrogens at positions 1 and 5 of the imidazole ring. Binds the benzodiazepine site of GABA-A receptors and enhances inhibitory neurotransmission. Compared with classical 1,4-benzodiazepines (diazepam, lorazepam), sedation and muscle-relaxant effects are less marked while the anticonvulsant effect remains. CYP3A4-metabolized to active N-desmethylclobazam with a 71–82-hour half-life. In Spain it is widely used as an antiepileptic under the brand Noiafren.
Adjunct
Adjunct in focal epilepsy in adults and children over 6 not controlled by monotherapy. ILAE 2017 and the Spanish SEN 2024 consensus place lamotrigine, levetiracetam, and lacosamide as first-line. Clobazam is added as a third or fourth agent. Standard starting dose 5–10 mg once daily at bedtime, titrated to 20–60 mg/day. Also used in Lennox–Gastaut and Dravet syndromes in children.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Clobazam is a long-acting benzodiazepine. It is prescribed for Lennox-Gastaut syndrome and focal epilepsy ( 2018 guidelines); a short course for anxiety in adults is described in the AEMPS Ficha Técnica, but with caution. For regular use in stress and anxiety in people without epilepsy or an anxiety disorder, clobazam is not used: the risks far outweigh the benefit. Regular benzodiazepine use causes tolerance, physical dependence, abuse risk, sedation, and a severe withdrawal syndrome on abrupt discontinuation (tremor, anxiety, insomnia, and in severe cases seizures). The boxed warning for benzodiazepines flags high dependence risk and dangerous consequences when combined with opioids. If clobazam was prescribed for stress, consider seeking a second opinion.
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Boxed warning
FDA boxed warning (2016): concurrent benzodiazepines and opioids carry risk of profound sedation, respiratory depression, and death. Co-prescribe only when alternatives are absent, at lowest effective doses and shortest duration.
T1 use carries a small increase in cleft lip/palate risk in some cohorts. T3 carries floppy infant syndrome and neonatal withdrawal risk. In pregnant patients with epilepsy, decisions are made with an epileptologist; therapy is not stopped without cause.
Clobazam is evaluated for the following indications with varying evidence strength: Focal epilepsy (evidence tier B), Stress and anxiety (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Clobazam (≥ 1 in 100): Drowsiness, Drooling, especially in older patients, Ataxia, Constipation, Irritability, Insomnia (paradoxical). See the Safety section for uncommon and serious reactions.
FDA category C. T1 use carries a small increase in cleft lip/palate risk in some cohorts. T3 carries floppy infant syndrome and neonatal withdrawal risk. In pregnant patients with epilepsy, decisions are made with an epileptologist; therapy is not stopped without cause.
Milk concentrations are low, but the active metabolite persists in the infant. Monitor drowsiness and weight gain; if pronounced sedation occurs in the infant, switch to formula.
Clobazam is contraindicated in: Benzodiazepine hypersensitivity; Severe respiratory failure; Severe hepatic impairment; Myasthenia gravis; Untreated obstructive sleep apnea. Full list in the Safety section.
Milk concentrations are low, but the active metabolite persists in the infant. Monitor drowsiness and weight gain; if pronounced sedation occurs in the infant, switch to formula.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
FDA boxed warning (2016): concurrent benzodiazepines and opioids carry risk of profound sedation, respiratory depression, and death. Co-prescribe only when alternatives are absent, at lowest effective doses and shortest duration.