Neuroactive Steroid GABA(A) Receptor-Positive Modulators

Postpartum depression (PPD) can cause feelings of overwhelming sadness, hopelessness, and anxiety for some new parents. Fortunately, there are various treatments available. A promising area of research is the use of neuroactive steroids that target GABA(A) receptors.^1,2

GABA(A) receptors, short for gamma-aminobutyric acid type A receptors, are vital parts of the brain's neurotransmitter system. They regulate anxiety, mood, and overall brain activity. GABA(A) receptor-positive modulators are also known as neuroactive steroids. These are substances that enhance the function of these receptors. In doing so, they may promote calm and stabilize moods.^1-3

How do neuroactive steroids work?

Neuroactive steroids work by increasing the activity of GABA(A) receptors in the brain. When GABA(A) receptors are activated, they help relax the central nervous system. This helps to relieve symptoms of anxiety and depression.³

How are they beneficial for postpartum depression?

PPD is a complex condition with both hormonal and psychological factors at play. GABA(A) receptor-positive modulators have shown promise in treating PPD because they are fast-acting and they are thought to help to:^1,2

• Stabilize mood
• Reduce anxiety
• Improve sleep

Examples of neuroactive steroid GABA(A) receptor-positive modulators

While research in this area is ongoing, some neuroactive steroids have shown great success in treating PPD. Two drugs have been approved by the US Food and Drug Administration (FDA) to treat postpartum depression:^1,2

• Brexanolone (Zulresso®)
• Zuranolone (Zurzuvae®)

Brexanolone is given as an intravenous (IV) infusion over a few days under medical supervision. Studies found that people who received this drug had significant improvements in depression symptoms within 60 hours after the drug was given.^1,2

Zuranolone is the first oral treatment for PPD. It was approved by the FDA in 2023. Zuranolone comes in a pill form and does not need to be taken under medical supervision. It may be used alone or in combination with another antidepressant.^1,2,4,5

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. Side effects of brexanolone and zuranolone may include:^4-6

• Sudden sedation (somnolence)
• Drowsiness and fatigue
• Dizziness
• Diarrhea
• Dry mouth
• Urinary tract infection (UTI)

Brexanolone has a boxed warning, the strictest warning from the FDA. It has this warning because it can cause excessive sedation and sudden loss of consciousness. For this reason, the drug is available only with a risk evaluation and mitigation strategy (REMS). The REMS requires the medicine to be given in a healthcare facility with a healthcare provider present.^1,2,6

Zuranolone also has a boxed warning. It has this warning because its sedating side effects can impact a person’s ability to drive and perform other tasks. This may be dangerous to the person’s health.^4,5

These are not all the possible side effects of neuroactive steroid GABA(A) receptor-positive modulators. Talk to your doctor about what to expect when taking neuroactive steroids. You also should call your doctor if you have any changes that concern you when taking these drugs.

Other things to know

Studies suggest that it is generally safe to take these drugs while breastfeeding. But neuroactive steroids may not be safe to take during pregnancy. According to animal studies, these drugs may cause harm to an unborn baby. Talk to your doctor if you are pregnant or planning to become pregnant or breastfeed.^4-6

Do not take these drugs if you have end-stage kidney disease.^5,6

These drugs may cause suicidal thoughts and behavior. If your PPD is getting worse or you have thoughts of self-harm or suicide, talk to your doctor as soon as possible. If you are in crisis, call or text the Suicide & Crisis Lifeline at 988.^4-6

Discuss the potential benefits and risks with a healthcare provider before starting any treatment for PPD. They can help determine whether neuroactive steroids are the right choice for you.

Before beginning treatment for postpartum depression, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.