What is the recommended dose of brexanolone (allopregnanolone) for treating postpartum depression?

Recommended Dosing of Brexanolone for Postpartum Depression

The recommended dose of brexanolone for treating postpartum depression is a 60-hour continuous intravenous infusion starting at 30 μg/kg/hour (0-4 hours), increasing to 60 μg/kg/hour (4-24 hours), then to 90 μg/kg/hour (24-52 hours), followed by a taper to 60 μg/kg/hour (52-56 hours) and finally to 30 μg/kg/hour (56-60 hours). 1, 2

Administration Protocol

Brexanolone (Zulresso) is administered as a single continuous intravenous infusion over 60 hours with the following titration schedule:

• Hours 0-4: 30 μg/kg/hour
• Hours 4-24: 60 μg/kg/hour
• Hours 24-52: 90 μg/kg/hour
• Hours 52-56: Decrease to 60 μg/kg/hour
• Hours 56-60: Decrease to 30 μg/kg/hour

This dosing regimen has been established through multiple clinical trials, including phase 2 and phase 3 studies that demonstrated significant and rapid improvement in postpartum depression symptoms 1, 2.

Clinical Efficacy

The efficacy of brexanolone at this dosing regimen has been well-documented:

• Significant reduction in Hamilton Depression Rating Scale (HAM-D) scores compared to placebo as early as 24 hours after starting infusion 3
• Median time to response is 24 hours versus 36 hours with placebo 3
• Treatment effects are durable, with benefits maintained through at least 30 days post-infusion 1
• Some studies show benefits extending 3-16 months post-treatment 4

Administration Considerations

• The infusion must be administered in a healthcare facility under close supervision due to risk of excessive sedation and loss of consciousness 5
• Continuous pulse oximetry monitoring is required during administration
• Patients should be monitored for at least 12 hours after the end of the infusion before discharge

Safety Precautions

• Brexanolone should be administered with or after feeding to reduce the risk of hypoglycemia, similar to other medications like propranolol 6
• Doses should be held during times of diminished oral intake or vomiting 6
• Due to the risk of excessive sedation, a Risk Evaluation and Mitigation Strategies (REMS) program is required 5
• The most common adverse effects include headache, dizziness, and somnolence 1, 2

Special Populations

• For patients with renal impairment, no dose adjustment is necessary as the drug is primarily metabolized through non-renal pathways
• For patients with hepatic impairment, careful monitoring is recommended as metabolism may be affected

Practical Implementation

• Treatment requires a 2.5-day hospital stay
• The healthcare facility must be certified in the REMS program
• A healthcare provider must be available on site to continuously monitor the patient during the entire infusion
• Patients must be enrolled in the REMS program prior to receiving treatment

This dosing regimen has demonstrated both rapid and sustained efficacy in treating postpartum depression, with clinically meaningful improvements in depressive symptoms, anxiety, and insomnia 3.