What is the typical dosage and usage of Clobazam (clobazam) for anxiety disorders and epilepsy?

Clobazam Dosing and Usage

Clobazam is FDA-approved specifically for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥2 years old, with weight-based dosing starting at 5-10 mg/day and titrating up to 20-40 mg/day; while it has demonstrated efficacy for anxiety disorders in research studies at 20-30 mg/day, this is not an FDA-approved indication. 1

FDA-Approved Indication: Epilepsy (Lennox-Gastaut Syndrome)

Dosing Algorithm by Body Weight

For patients ≤30 kg:

• Start at 5 mg/day (can be given as single dose)
• Day 7: Increase to 10 mg/day (divided twice daily)
• Day 14: Increase to 20 mg/day (divided twice daily) 1

For patients >30 kg:

• Start at 10 mg/day (divided twice daily)
• Day 7: Increase to 20 mg/day (divided twice daily)
• Day 14: Increase to 40 mg/day (divided twice daily) 1

Critical Dosing Principles

• Do not escalate faster than weekly intervals because clobazam requires 5 days and its active metabolite (N-desmethylclobazam) requires 9 days to reach steady-state 1
• Doses >5 mg/day must be divided into twice-daily administration 1
• Can be taken with or without food 1

Special Population Adjustments

Elderly patients:

• Start at 5 mg/day regardless of weight
• Titrate to half the standard doses in Table 1
• If needed, may increase to maximum dose (20 or 40 mg/day based on weight) starting day 21 1

CYP2C19 poor metabolizers:

• Start at 5 mg/day
• Titrate to half the standard doses due to increased levels of active metabolite
• Maximum dose escalation may begin day 21 if clinically necessary 1

Hepatic impairment:

• Proceed slowly with dose escalations (limited data available)
• No specific dosing recommendations for severe hepatic impairment 1

Renal impairment:

• No adjustment needed for mild-moderate impairment
• No data for severe renal impairment or ESRD 1

Off-Label Use: Anxiety Disorders (Not FDA-Approved)

Research Evidence for Anxiety

While not FDA-approved for anxiety, research studies have demonstrated efficacy at specific doses:

• 20-30 mg/day has shown benefit for anxiety disorders in multiple clinical trials 2, 3, 4
• Single nightly dosing of 20-30 mg was therapeutically equivalent to divided dosing for anxiety 2, 3, 4
• 20 mg single nightly dose showed good anxiolysis without hangover effects and was equivalent to diazepam 5 mg twice daily 4
• Clobazam demonstrated better motor performance compared to diazepam in anxiety patients 4

Important Caveats for Anxiety Use

The evidence for anxiety is from older studies (1979-1986) and clobazam is not currently approved for this indication in the USA 1. Standard WHO guidelines for anxiety management in low-resource settings do not include clobazam, instead recommending other benzodiazepines like lorazepam (0.5-1 mg four times daily) for anxiety 5.

Critical Safety Warnings

Boxed Warnings (All Indications)

Concomitant opioid use:

• May cause profound sedation, respiratory depression, coma, and death
• Reserve combination only when alternatives are inadequate
• Use minimum effective doses and durations 1

Abuse, misuse, and addiction risk:

• Assess each patient's risk before prescribing and throughout treatment
• Commonly involves concomitant use of other medications, alcohol, or illicit substances 1

Physical dependence and withdrawal:

• Abrupt discontinuation can precipitate life-threatening withdrawal reactions
• Taper by decreasing 5-10 mg/day on a weekly basis when discontinuing
• If withdrawal symptoms develop, pause taper or increase to previous dose level 1

Additional Warnings

• Monitor for somnolence/sedation, especially with other CNS depressants 1
• Serious dermatological reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis): discontinue at first sign of rash unless clearly not drug-related 1
• Monitor for suicidal behavior and ideation 1
• Increased seizure frequency and status epilepticus risk with abrupt discontinuation 1

Mechanism and Pharmacology

Clobazam is a 1,5-benzodiazepine (unlike most benzodiazepines which are 1,4-benzodiazepines) that allosterically activates GABA-A receptors 6. It binds less to subunits mediating sedative effects compared to other benzodiazepines, potentially explaining its favorable tolerability profile 6. The elimination half-life is approximately 18 hours, with an active metabolite (N-desmethylclobazam) contributing to prolonged therapeutic effect 6, 3.