Zuranolone: Does it Work? Benefits & FDA Status [Sep. 2023]

Zuranolone is an investigative oral drug to treat depression, insomnia, and Parkinson’s disease. It was developed primarily by improving brexanolone (allopregnanolone), which is administered by injection.

After completing phase III clinical trials, Biogen and Sage Therapeutics, Inc. submitted a New Drug Application for zuranolone to treat major depressive disorder and postpartum depression. On August 4, 2023, the U.S. Food and Drug Administration (FDA) approved zuranolone for postpartum depression.

Read on to learn what to expect shortly, how zuranolone works, who it’s for, what side effects it may cause, and more.

What is zuranolone?

Zurzuvae (zuranolone) is a new FDA-approved drug for postpartum depression. It may also treat major depressive disorder.

This drug has completed phase III clinical trials, where it showed rapid improvement over the placebo on multiple days. Side effects were minimal, especially compared to other antidepressants currently available, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants.

Zuranolone is taken orally every day for 14 days. The fact that zuranolone may be an effective fast-acting oral medication for postpartum depression is a big deal, as the only medication previously approved for this condition is administered only by IV. The short treatment course may lead to lower healthcare costs and better outcomes for women with postpartum depression.

Better Than Brexanolone

Zuranolone improves upon brexanolone (brand name: Zulresso), which was FDA-approved in 2019. This drug is administered by venous injection.

However, zuranolone has higher oral absorption and a longer half-life than ​​brexanolone. In layman’s terms, your body absorbs it better, so zuranolone is, therefore, more effective.

The longer half-life of zuranolone over brexanolone (up to 23 hours, compared to 9 hours) allows patients to take zuranolone less often.

These improvements make zuranolone more accessible for patients to take (and afford).

What class of drug is zuranolone?

Zuranolone is a neuroactive steroid. This antidepressant drug is an inhibitory pregnane neurosteroid and a GABA-A receptor-positive allosteric modulator.

Is zuranolone FDA-approved?

Yes, the FDA approved zuranolone (brand name Zurzuvae) for postpartum depression on August 4, 2023, after being submitted to the FDA in December 2022.

How Zuranolone Works

How does zuranolone work? Zuranolone works by rapidly rebalancing dysregulated neuron networks. This rebalancing is supposed to reset and maintain healthy brain function.

This drug is an inhibitory pregnane neurosteroid. This means zuranolone blocks specific neurons from getting excited, which could lead to feelings of depression.

Pregnane is an indirect parent of progesterone, a hormone associated with GABA. Low GABA levels are associated with anxiety and depression. Keeping those GABA levels from dropping may prevent depressive symptoms.

Related reading: NAD (Nicotinamide Adenine Dinucleotide): Benefits & How It Works

Here’s What the Research Tells Us

Biogen and Sage organized 2 clinical development programs (LANDSCAPE and NEST), which included 7 advanced studies. LANDSCAPE included MDD-201B, MOUNTAIN, WATERFALL, CORAL, and SHORELINE (an open-label study). The NEST program included the SKYLARK and ROBIN studies.

Many studies have gone into zuranolone’s benefits, but let’s focus on these 3 phase III clinical trials:

• In the phase III MOUNTAIN study, 30 grams of zuranolone a day improved depression significantly over the placebo at days 3, 8, and 12 out of 14.
• In the phase III CORAL study, 50 grams of zuranolone a day seemed to perform better than the MOUNTAIN study’s 30 grams daily. This intervention study met its primary goal of showing improvement at Day 3 of treatment. No signs of suicidal ideation or withdrawal were observed.
• In the phase III SKYLARK study, which is newer than CORAL, CORAL’s results were largely confirmed and expounded upon. SKYLARK met its primary endpoint of showing improvement at Day 15 of treatment (one day after the 14-day treatment course ended), according to the Hamilton Anxiety Rating Scale (HAMD-17) total score.

Side Effects

Treatment-emergent adverse effects have occurred in fewer than 5-10% of patients in clinical trials — an excellent safety profile for an antidepressant. These side effects include:

• Sedation
• Somnolence (feeling drowsy and/or having a strong desire to go to sleep)
• Headache
• Fatigue
• Dizziness
• Diarrhea
• Nausea

Zuranolone was designed as an improvement over brexanolone, utilizing similar mechanisms of action. The adverse events may not be the same, but it’s worth noting that brexanolone side effects also include fainting and a spinning sensation.

How Long Does Zuranolone Last?

Zuranolone has a half-life of up to 23 hours, meaning you only have to take it once daily. Results show up by Day 3.

Studies have indicated the benefits of zuranolone may last 2-5 months after treatment. One study found that depression symptoms were minimal or mild after a year.

In one ongoing study, researchers set a minimum of 56 days between 14-day courses of zuranolone, allowing for up to 5 courses over a year.

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Looking to the Future

Zuranolone seems to be a rapid-acting, once-daily oral medication for depression — something you take for 2 weeks, lasting more than 2 months. Its side effects are minimal and rare. This is very exciting news in the world of pharmacology.

Do you live in Colorado and struggle with depression? Schedule a consultation at PrimeHealth for a holistically-minded approach to reversing depression for good.

Sources

1. Clayton, A. H., Lasser, R., Nandy, I., Sankoh, A. J., Jonas, J., & Kanes, S. J. (2023). Zuranolone in Major Depressive Disorder: Results From MOUNTAIN—A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial. The Journal of Clinical Psychiatry, 84(2), 45750.
2. Deligiannidis, K. M., Meltzer-Brody, S., Gunduz-Bruce, H., Doherty, J., Jonas, J., Li, S., … & Lasser, R. (2021). Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial.JAMA psychiatry, 78(9), 951-959.