How do I transition a patient from Xanax (alprazolam) to Klonopin (clonazepam)?

Transitioning from Alprazolam (Xanax) to Clonazepam (Klonopin)

Switch directly from alprazolam to an equivalent dose of clonazepam using a 1:1 mg ratio (e.g., alprazolam 1 mg = clonazepam 1 mg), which eliminates interdose anxiety and allows less frequent dosing while maintaining panic control. 1

Rationale for the Switch

• Clonazepam's longer half-life (18-50 hours) provides more continuous anxiety control throughout the day compared to alprazolam's shorter half-life (6-12 hours), eliminating the interdose anxiety ("clock-watching") that occurs with alprazolam. 1
• In a study of 48 patients switched from alprazolam to clonazepam for panic disorder, 82% rated clonazepam as "better" due to decreased dosing frequency and absence of interdose anxiety. 1
• Both medications demonstrate comparable efficacy for panic disorder at equivalent doses, but clonazepam permits twice-daily or even once-daily dosing versus alprazolam's typical three to four times daily requirement. 2, 1

Direct Conversion Protocol

Use a 1:1 mg conversion ratio when switching from alprazolam to clonazepam:

• Calculate the patient's total daily alprazolam dose (e.g., if taking alprazolam 0.5 mg four times daily = 2 mg/day total)
• Convert directly to the same total daily dose of clonazepam (2 mg alprazolam/day → 2 mg clonazepam/day) 1
• Divide the clonazepam dose into twice-daily administration (e.g., 1 mg twice daily) or, if tolerated, once daily at bedtime 1
• Make the switch abruptly rather than tapering, as the cross-tolerance between these benzodiazepines allows direct substitution 1

Dosing Considerations

• The typical effective dose range for clonazepam in panic disorder is 0.5-2.0 mg at bedtime, though some patients require up to 4.0 mg daily. 3
• Start with the equivalent converted dose, but be prepared to adjust based on response within the first week 1
• Approximately 20% of patients experience unacceptable sedative effects with clonazepam or inadequate anxiety reduction, requiring dose adjustment or alternative treatment 2
• For elderly, frail, or patients with COPD, use lower starting doses (0.25-0.5 mg) to minimize sedation and respiratory depression risk. 4

Monitoring During Transition

• Follow up within the first week after switching to assess for adequate panic control and monitor for excessive sedation, which is clonazepam's most common adverse effect. 2, 1
• Patients should report any breakthrough panic attacks, increased anxiety, or sedation that interferes with daily functioning 1
• Monitor for signs of respiratory depression, particularly in patients with compromised respiratory function (COPD, sleep apnea), as clonazepam can cause respiratory depression 5
• Check for orthostatic hypotension and fall risk, especially in elderly patients 4

Common Pitfalls and How to Avoid Them

• Do not attempt a gradual cross-taper between alprazolam and clonazepam—the direct switch is both safe and more effective due to cross-tolerance. 1
• Avoid underestimating clonazepam's sedative effects, particularly when administered during daytime hours; consider giving a larger portion of the dose at bedtime. 4
• Do not use clonazepam concomitantly with opioids except when alternative treatments are inadequate, as this combination significantly increases risk of respiratory depression, coma, and death 5
• Warn patients that clonazepam impairs cognitive and motor performance; they should not drive or operate machinery until they know how the medication affects them. 5
• Discontinuing alprazolam is particularly difficult and associated with serious rebound and withdrawal symptoms, but the direct switch to clonazepam avoids this problem 2

Special Populations

• In patients with renal impairment, use caution as clonazepam metabolites are renally excreted and may accumulate. 5
• Patients with hepatic impairment require reduced clonazepam dosing 6
• Avoid clonazepam in patients with severe pulmonary insufficiency, severe liver disease, or myasthenia gravis unless the patient is imminently dying. 4
• Counsel patients of childbearing potential about pregnancy risks and encourage enrollment in the North American Antiepileptic Drug Pregnancy Registry (1-888-233-2334) if pregnancy occurs 5

Long-Term Considerations

• Both alprazolam and clonazepam carry risks of abuse, misuse, addiction, and physical dependence, which can lead to overdose and death. 5
• If future discontinuation of clonazepam becomes necessary, taper gradually by 0.25 mg per week to avoid withdrawal symptoms, which can be life-threatening (including seizures) 5, 7
• The recommended tapering schedule after intermediate-term use is 0.25 mg/week reduction, which successfully discontinues clonazepam in most patients without major withdrawal symptoms 7
• Abrupt discontinuation or rapid dosage reduction can precipitate acute withdrawal reactions including seizures; always use a gradual taper. 5