Benzodiazepine Dose Conversion: Alprazolam to Clonazepam
For a patient taking 2mg of alprazolam (Xanax) daily, the equivalent clonazepam (Klonopin) dose is approximately 1mg daily, based on the standard 2:1 potency ratio between these benzodiazepines. 1
Conversion Ratio and Dosing
The standard benzodiazepine equivalency ratio between alprazolam and clonazepam is 2:1, meaning 2mg of alprazolam equals roughly 1mg of clonazepam based on comparative potency studies. 1
For patients taking alprazolam 2mg three times daily (6mg total), the clonazepam equivalent would be approximately 3mg daily, typically divided as 1mg TID or 1.5mg BID. 1
The minimum effective daily dose of clonazepam for panic disorder is 1.0mg, with doses of 1.0-2.0mg offering the best balance of therapeutic benefit and tolerability. 2
Critical Pharmacokinetic Differences
Clonazepam has a significantly longer half-life (30-40 hours) compared to alprazolam (6-12 hours), which fundamentally changes dosing dynamics and allows for less frequent dosing with more continuous anxiety control. 1
The longer half-life means slower onset of withdrawal symptoms if a dose is missed and greater drug accumulation with repeated dosing. 1
Due to these pharmacokinetic differences, clonazepam typically requires only once or twice daily dosing, whereas alprazolam often requires three to four times daily administration. 1
Safety Warnings and Monitoring
Clonazepam carries significant risks including morning sedation and cognitive impairment, reported in up to 58% of patients in some studies. 1
Clonazepam use is associated with risk of falls and confusion, especially at doses ≥2mg, with potential for subdural hematoma. 1
Clonazepam may worsen sleep apnea, even at doses of 0.5-1.0mg. 1
Before initiating conversion, screen for sleep apnea, gait disorders, and liver disease, and perform baseline cognitive and motor coordination assessment. 1
Monitor regularly for excessive sedation, cognitive function, fall risk, and signs of respiratory depression if sleep apnea is present. 1
Conversion Protocol
Perform gradual cross-titration when switching between benzodiazepines, informed by the half-life and receptor profile of each medication. 3
Start clonazepam at the equivalent dose (1mg for 2mg alprazolam) while gradually tapering alprazolam over 1-2 weeks to minimize withdrawal symptoms and rebound anxiety.
CYP3A4 expression is the major determinant of clonazepam plasma concentrations, with low expressers requiring substantially lower doses (0.029 mg/kg) compared to normal expressers (0.058 mg/kg bodyweight). 4
Discontinuation Considerations
Discontinuation of clonazepam can be challenging, with patients typically unable to substantially reduce doses despite tapering attempts. 1
When discontinuing clonazepam after intermediate-term use, reduce the dosage by 0.25mg per week after reaching 1mg daily, preceded by 0.5mg reductions every 2 weeks at higher doses. 5
Withdrawal symptoms are mostly mild and include anxiety, tremor, nausea, insomnia, excessive sweating, tachycardia, headache, weakness, and muscle aches. 5
Same-night relapse can occur if clonazepam is missed, highlighting the importance of adherence during maintenance therapy. 1