What is the likelihood of daytime sedation in a postpartum patient taking zuranolone (suvorexant), given her upcoming sole responsibility for infant care?

From the Guidelines

You should be concerned about your postpartum patient caring for her infant alone while taking zuranolone, given the potential for significant sedation. In clinical trials, approximately 15-20% of patients reported somnolence or sedation, which typically peaks within 1-3 hours after dosing and can last several hours 1. Consider advising your patient to take the medication at bedtime to minimize daytime impairment. Also, recommend having someone check on her during the first few days of treatment if possible, especially during the morning hours. Warn her against driving or operating dangerous equipment while taking zuranolone. The sedative effects often diminish after the first few days of the 14-day treatment course as patients adjust to the medication. Zuranolone works as a positive allosteric modulator of GABA-A receptors, similar to benzodiazepines but with a different binding site, which explains its sedative properties. If sedation is too problematic, alternative treatments for postpartum depression should be considered. Some studies suggest that sedated mothers are at higher risk for accidents and injuries, particularly when caring for newborns, and that increased staff vigilance and monitoring can help mitigate these risks 1. Given the potential risks, it is essential to prioritize the patient's safety and the safety of her infant, and to consider alternative arrangements for childcare if necessary. Ultimately, the decision to prescribe zuranolone should be made with caution and careful consideration of the potential risks and benefits, and with close monitoring of the patient's response to the medication.

From the FDA Drug Label

The most common adverse reactions (≥5% and greater than placebo) in ZURZUVAE-treated patients were somnolence, dizziness, diarrhea, fatigue, and urinary tract infection Somnolence includes sedation and hypersomnia The most common adverse reaction leading to treatment discontinuation in ZURZUVAE-treated patients was somnolence Dosage reduction due to an adverse reaction occurred in 14% of ZURZUVAE-treated patients The most common adverse reactions leading to dosage reduction in ZURZUVAE-treated patients were somnolence (10%) and dizziness (6%) CNS Depressant Drugs and Alcohol: Clinical Impact: Due to additive pharmacological effects, the concomitant use of CNS depressant drugs, including alcohol, may increase impairment of psychomotor performance or CNS depressant effects

Sedation is a common adverse reaction associated with zuranolone, with somnolence (including sedation and hypersomnia) reported in 36% of patients in Study 1. This may impact the patient's ability to care for the baby.

• Key considerations:
  • Somnolence was the most common adverse reaction leading to treatment discontinuation
  • Dosage reduction due to somnolence occurred in 10% of patients
  • Concomitant use of CNS depressant drugs or alcohol may increase the risk of sedation and impairment of psychomotor performance 2

From the Research

Sedation Effects of Zuranolone

• The most common adverse events reported with zuranolone use were somnolence, dizziness, sedation, and headache 3.
• In a double-blind phase 3 trial, the most common adverse events (≥10%) with zuranolone were somnolence, dizziness, and sedation 4.
• Zuranolone was well tolerated, with somnolence, dizziness, headache, and sedation reported as the most common side effects 5.

Impact on Daily Activities

• There is no direct evidence on how sedation from zuranolone affects daily activities, such as taking care of a baby.
• However, the fact that zuranolone can cause sedation suggests that it may impact the patient's ability to perform daily tasks, especially those that require attention and alertness 3, 4, 5.

Clinical Decision-Making

• Key aspects of clinical decision-making in patients with postpartum depression, including the use of zuranolone, are discussed in the literature 3.
• The integration of zuranolone into clinical practice may significantly improve the quality of life for mothers facing the challenges of postpartum depression, but ongoing research and post-marketing surveillance are essential to further elucidate its long-term safety and efficacy 6.