Yes, Zurzuvae (zuranolone) can cause headaches, though this is not one of the most common side effects.
Headache Incidence from FDA Drug Label
According to the FDA-approved prescribing information, headache occurred in patients treated with Zurzuvae but was not among the most frequently reported adverse reactions 1. The drug label specifically lists the most common adverse reactions (≥5% and greater than placebo) as somnolence, dizziness, diarrhea, fatigue, and urinary tract infection—notably, headache is not included in this primary list 1.
Detailed Safety Profile
In the pivotal Study 1 (50 mg dose), headache was not reported at a rate of ≥2% in the adverse reaction tables, suggesting it occurred in fewer than 2% of patients at a higher rate than placebo 1. This indicates headache is a relatively uncommon side effect compared to the predominant adverse reactions.
Most Common Side Effects to Anticipate
The adverse reactions you should primarily counsel patients about include:
- Somnolence (36% vs 16% placebo) - by far the most common
- Dizziness (13% vs 9% placebo)
- Diarrhea (6% vs 2% placebo)
- Fatigue (5% vs 2% placebo)
- Urinary tract infection (5% vs 4% placebo)
Evidence from Meta-Analysis
A 2024 systematic review and meta-analysis examining zuranolone across multiple studies found that headache showed no significant overall difference between zuranolone and placebo (OR = 1.11,95% CI: [0.84,1.47], p = 0.47) 2. Interestingly, dose-dependent analysis revealed that the 30 mg group actually had less headache than placebo, suggesting headache is not a characteristic adverse effect of this medication 2.
Clinical Context
In the broader depression literature examining zuranolone, headache appears occasionally in lists of common side effects alongside somnolence, dizziness, and nausea 3, 4, but it consistently ranks below the primary CNS depressant effects that define this medication's tolerability profile.
Key Clinical Takeaway
While headache can occur with Zurzuvae, it is not a defining or particularly common adverse reaction. The medication's side effect profile is dominated by CNS depressant effects (somnolence, dizziness, sedation) that occur at substantially higher rates and should be the primary focus of patient counseling and monitoring 1.