What is the recommended dose of clonazepam (Klonopin) for adults and children?

Clonazepam Dosing Recommendations

For adults with seizure disorders, start with no more than 1.5 mg/day divided into three doses, increasing by 0.5-1 mg every 3 days up to a maximum of 20 mg/day; for panic disorder, start with 0.25 mg twice daily, targeting 1 mg/day after 3 days with a maximum of 4 mg/day; for children with seizures, start with 0.01-0.03 mg/kg/day (not exceeding 0.05 mg/kg/day) in divided doses, increasing by 0.25-0.5 mg every third day to a maintenance dose of 0.1-0.2 mg/kg/day. 1

Adult Dosing by Indication

Seizure Disorders

• Initial dose: Maximum 1.5 mg/day divided into three doses 1
• Titration: Increase by 0.5-1 mg every 3 days until seizures are controlled or side effects occur 1
• Maintenance: Individualized based on response 1
• Maximum dose: 20 mg/day 1
• The therapeutic serum concentration ranges from 5-50 ng/mL with a biological half-life of 22-32 hours 2

Panic Disorder

• Initial dose: 0.25 mg twice daily 1
• Target dose: 1 mg/day after 3 days, which is optimal for most patients 1
• Titration: If needed, increase by 0.125-0.25 mg twice daily every 3 days 1
• Maximum dose: 4 mg/day (though higher doses may be less effective and cause more adverse effects) 1
• To minimize somnolence, consider administering one dose at bedtime 1

Depression (Adjunctive Treatment)

• Recommended dosage: 2.5-6.0 mg/day in combination with SSRIs 3
• Response timeline: If effective, response should be observed within 2-4 weeks 3
• More effective for unipolar than bipolar depression 3

REM Sleep Behavior Disorder

• Starting dose: 0.25-0.5 mg at bedtime 4
• Typical effective range: 0.25-1.0 mg at bedtime 4
• Women may require higher doses (mean 1.4 mg) compared to men (mean 0.68 mg) 4

Acute Agitation (Emergency Setting)

• Dose range: 1-2 mg intramuscularly or orally 5
• Produces rapid reduction in agitation within 2 hours, though haloperidol may work more rapidly at the 1-hour endpoint 5

Pediatric Dosing

Seizure Disorders (Children up to 10 years or 30 kg)

• Initial dose: 0.01-0.03 mg/kg/day (not exceeding 0.05 mg/kg/day) given in 2-3 divided doses 1
• Titration: Increase by no more than 0.25-0.5 mg every third day 1
• Maintenance dose: 0.1-0.2 mg/kg/day 1
• Divide daily dose into three equal doses when possible; if unequal, give largest dose before bedtime 1

Panic Disorder in Children

• No established clinical trial data exists for panic disorder in patients under 18 years of age 1

Special Population Considerations

Elderly Patients

• General approach: Start on low doses and observe closely 1
• Starting dose for anxiety/sleep: 0.25 mg once daily 6
• Pain management: Start with 0.25-0.5 mg at bedtime; elderly rarely tolerate doses greater than 30-40 mg per day 4
• Clonazepam appears on the American Geriatrics Society Beers Criteria as potentially inappropriate in older adults 7, 4
• Monitor for falls, confusion, memory impairment, and sedation 4

Hepatic Impairment

• Use lower starting doses (0.25 mg once daily) 6
• Consider lorazepam (0.5-1 mg) as an alternative due to simpler metabolism 6
• Contraindicated in severe liver disease 4

Patients with Sleep Apnea

• Use with extreme caution as clonazepam may worsen or cause sleep apnea at doses of 0.5-1.0 mg 7, 4
• Consider melatonin (3-12 mg at bedtime) as an alternative, particularly for REM sleep behavior disorder 7

Critical Safety Considerations

Common Side Effects

• Most frequent: Somnolence, particularly morning sedation 4
• Other effects: Ataxia, confusion, memory dysfunction, early morning motor incoordination 4, 2
• Side effects tend to be dose-related, occur early in therapy, and may subside with chronic administration 2

Serious Risks

• Falls and confusion: Especially at doses of 2.0 mg nightly 4
• Respiratory depression: Risk increases when combined with other CNS depressants 4
• Fatal interactions: Combining with benzodiazepines and high-dose olanzapine has resulted in fatalities 4
• Seizure risk: Abrupt discontinuation can cause withdrawal seizures 4

Contraindications

• Severe pulmonary insufficiency 4
• Severe liver disease 4
• Myasthenia gravis 4
• Parkinson's disease or dementia with Lewy bodies (when used for delirium) 4

Discontinuation Protocol

Gradual Tapering Required

• Panic disorder: Decrease by 0.125 mg twice daily every 3 days until completely withdrawn 1
• After intermediate-term use: Reduce by 0.25 mg per week 8
• After long-term use (≥3 years): Decrease by 0.5 mg per 2-week period until 1 mg/day is reached, then decrease by 0.25 mg per week 8
• Most withdrawal symptoms are mild and include anxiety, tremor, nausea, insomnia, sweating, tachycardia, headache, and muscle aches 8
• 68.9% of patients can successfully discontinue within 4 months using this protocol 8

Pharmacokinetic Properties

Absorption and Bioavailability

• Oral bioavailability: 90% 9
• Intramuscular bioavailability: 93% 9
• Time to peak (oral): 1.7 hours 9
• Time to peak (IM): 3.1 hours (with possible secondary peaks at 10.4 hours) 9
• Rapidly absorbed and passes quickly from blood to brain 2

Distribution and Elimination

• Half-life: 22-32 hours 2, with some studies showing 38-43.6 hours 9
• Volume of distribution: 180 liters 9
• Clearance: 55 mL/min 9
• The long half-life (30-40 hours) can lead to daytime sedation and compromised functioning 7

Clinical Pearls

• Start low and titrate slowly to minimize drowsiness, ataxia, and behavioral changes 2
• Tolerance to anticonvulsant effects may develop with chronic administration 2
• For seizure prophylaxis during high-dose busulfan chemotherapy, use 1 mg every 8 hours starting 12 hours before busulfan until 48 hours after completion 10
• Morning drowsiness is the most common side effect requiring dose adjustment or timing modification 6
• Use caution in patients with neurodegenerative disorders due to increased confusion risk 6