What is the diazepam dose equivalent for an adult switching from alprazolam 0.5 mg twice daily?

Benzodiazepine Conversion: Alprazolam to Diazepam

For an adult transitioning from alprazolam 0.5 mg twice daily (1 mg total daily), the equivalent diazepam dose is 10 mg daily, typically given as 5 mg twice daily. 1, 2

Conversion Ratio and Evidence Base

The standard conversion ratio is 1 mg alprazolam = 10 mg diazepam, based on comparative efficacy trials demonstrating equivalent anxiolytic effects at these dose ratios. 1, 2

• In controlled trials, alprazolam 1.5 mg daily was therapeutically equivalent to diazepam 15 mg daily, establishing a 1:10 potency ratio. 1
• A separate study confirmed that alprazolam 1.5-3 mg daily produced equivalent anxiolytic effects to diazepam 15-30 mg daily, reinforcing this conversion factor. 2

Practical Conversion Strategy

Initial conversion should use the full calculated equivalent dose (10 mg diazepam daily), divided into twice-daily dosing to match the patient's current alprazolam schedule. 1, 2

• Start with diazepam 5 mg twice daily (morning and evening) to maintain consistent benzodiazepine coverage throughout the day.
• The longer half-life of diazepam (20-100 hours vs. alprazolam's 12-15 hours) provides more stable plasma levels and reduces interdose anxiety. 3

Critical Dose Adjustments for Special Populations

Elderly patients require a 50% dose reduction: Start with diazepam 2.5 mg twice daily (5 mg total daily) due to decreased clearance and increased sensitivity. 4

• Alprazolam clearance in elderly patients is significantly reduced (0.54-0.62 ml/min/kg) with half-lives exceeding 21 hours, indicating prolonged drug accumulation. 3
• Elderly patients experience greater psychomotor impairment and sedation at equivalent doses. 3

Patients with hepatic or renal impairment: Reduce the initial diazepam dose by 30-50% (start with 3.5-5 mg daily) due to reduced clearance of both medications. 4, 5

Concurrent opioid use: Reduce diazepam dose by 30% (start with 7 mg daily, divided) due to synergistic respiratory depression risk. 4

Common Pitfalls to Avoid

• Incomplete cross-tolerance: Although alprazolam and diazepam are both benzodiazepines, some patients may experience mild withdrawal symptoms during the first 48-72 hours of conversion due to pharmacokinetic differences. 6
• Timing of conversion: Do not taper alprazolam before switching—perform an abrupt substitution with the full equivalent diazepam dose to prevent withdrawal symptoms. 6
• Paradoxical reactions: Diazepam may cause paradoxical excitement or agitation in 1-7% of patients, particularly in elderly or frail individuals; monitor closely during the first week. 4
• Fall risk: All benzodiazepines increase fall risk in elderly patients; counsel on fall prevention strategies regardless of which agent is used. 4

Monitoring During Transition

Monitor for withdrawal symptoms (anxiety, tremor, insomnia, irritability) during the first 3-5 days after conversion, as alprazolam's shorter half-life may result in transient gaps in benzodiazepine coverage until diazepam reaches steady state. 3

• If breakthrough anxiety occurs, consider temporarily increasing the diazepam dose by 2.5-5 mg daily rather than reverting to alprazolam. 6
• Reassess the patient at 1 week to ensure adequate symptom control and absence of excessive sedation. 4