Zuranolone is a prescription medication used to treat postpartum depression in adults. Sold under the brand name Zurzuvae, it is a neuroactive steroid that increases the activity of GABA-A receptors, which are involved in regulating activity in the brain.
In the United States, zuranolone is FDA-approved specifically for postpartum depression and is not approved for major depressive disorder. Unlike antidepressants that may be taken for months or longer, zuranolone is given as a short 14-day course.
Zuranolone is available as oral capsules and is normally taken once each evening with food that contains fat. Because the medication can cause significant sleepiness and affect the ability to drive safely, several precautions are needed during treatment.
Indications
Zuranolone is indicated for the treatment of postpartum depression in adults.
Postpartum depression is a depressive disorder that develops during pregnancy or after childbirth. Clinical trials have found that zuranolone can reduce symptoms of postpartum depression after a 14-day treatment course.
In one phase 3 study using 30 mg of zuranolone daily, improvement in depression symptoms was greater with zuranolone than with placebo by the end of treatment. Benefits were still observed during follow-up through day 45.
Another phase 3 trial evaluated the 50 mg dose that is now recommended by the FDA. Participants treated with zuranolone had greater improvement in depression scores at day 15 compared with those who received placebo, with differences also reported earlier in treatment and during follow-up.
Zuranolone is not FDA-approved for major depressive disorder, postpartum blues, general anxiety, bipolar depression or depression during pregnancy.
How to take it
The recommended dose of zuranolone is 50 mg by mouth once daily in the evening for 14 days.
Each dose should be taken with a meal that contains fat. Zuranolone is available only as oral capsules, including 20 mg, 25 mg and 30 mg strengths. There are currently no liquid, injectable or extended-release forms.
If significant effects on the central nervous system occur, such as excessive sleepiness or sedation, the dose may be reduced to 40 mg once daily in the evening for the remainder of the 14-day course.
A lower dose of 30 mg once daily for 14 days is recommended for people taking strong CYP3A4 inhibitors. This dose is also recommended for people with severe liver impairment or moderate to severe kidney impairment.
Treatment consists of one 14-day course. The safety and effectiveness of taking zuranolone for longer than 14 days or receiving repeated treatment courses have not been established.
Possible side effects
The most common side effects associated with zuranolone include:
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Sleepiness or somnolence
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Dizziness
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Diarrhea
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Fatigue
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Sedation
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Nasopharyngitis, which can cause symptoms similar to a common cold
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Urinary tract infection
Sleepiness and sedation are particularly important because zuranolone can impair mental alertness and coordination.
Other clinically important effects can include confusion, memory problems and an increased risk of falls. As with other medications used to treat depression, worsening depression or suicidal thoughts and behavior also require prompt medical assessment.
Warnings and precautions
Driving and hazardous activities
Zuranolone carries an important warning about impaired ability to drive or perform other potentially hazardous activities.
Driving, operating machinery or performing other hazardous activities should be avoided for at least 12 hours after each dose throughout the 14-day treatment course. A person may not be able to accurately judge the degree of impairment caused by the medication.
Alcohol and other sedating medications
Alcohol and medicines that slow the central nervous system can increase sleepiness, sedation and problems with coordination when combined with zuranolone.
Examples include benzodiazepines, opioids, tricyclic antidepressants and other medications that cause central nervous system depression. A review of medications being taken is therefore important before treatment begins.
Drug interactions
Zuranolone is affected by medicines that alter the activity of the CYP3A4 enzyme.
Strong CYP3A4 inhibitors can increase exposure to zuranolone, which is why a lower dose may be required. CYP3A4 inducers can reduce exposure to the medication and may reduce its effectiveness.
Frequently asked questions
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Yes. Zuranolone is a controlled substance in the United States because it has the potential for misuse and dependence.
It should be taken only at the prescribed dose and for the recommended treatment period.
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Zuranolone may begin improving postpartum depression symptoms within the first few days of treatment. In a phase 3 trial of the 50 mg dose, improvement compared with placebo was reported by day 3.
Benefits were also seen at the end of the 14-day treatment course and during follow-up on days 28 and 45.
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Zuranolone passes into breast milk in small amounts. A study found that estimated infant exposure through breast milk was low, including with the 50 mg dose.
However, the effects of zuranolone on breastfed infants have not been established, so the potential benefits and risks should be considered before breastfeeding during treatment.
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Zuranolone can cause harm to a developing fetus and carries a warning for embryo-fetal toxicity.
Pregnancy status and reproductive considerations should therefore be assessed before treatment when appropriate.
Contraindications
The FDA prescribing information does not list any formal contraindications for zuranolone.
However, the medication has several important warnings and precautions. Particular care is needed because of the risk of severe sleepiness, impaired driving ability, central nervous system depression, suicidal thoughts or behavior, fetal harm, drug interactions and the potential for misuse or dependence.
Dose adjustments may also be necessary in people with severe liver impairment, moderate to severe kidney impairment or those taking strong CYP3A4 inhibitors.