New antidepressant medications

According to the World Health Organization (WHO), depression is a leading cause of disability worldwide, affecting over 264 million people.

The National Center for Health Statistics reports approximately 12.7% of Americans ages 12 and up used antidepressant medications in the past month, according to data from 2011 to 2014. 

The Food and Drug Administration (FDA) recently approved two new antidepressant medications that represent new approaches to treating depression: brexanolone and esketamine.

Both of these medications carry a black box warning, which is the most serious warning from the FDA. It alerts you of potentially serious drug effects. 

For brexanolone, there’s a warning for excessive sedation and sudden loss of consciousness. People taking this drug should have continuous pulse oximetry monitoring and must be accompanied during interactions with children.

For esketamine, warnings include:

  • Sedation and dissociation. After each treatment session, people who take this drug should be monitored for at least 2 hours.
  • Abuse and misuse.
  • Suicidal thoughts and behaviors. Antidepressants increase the risk of suicidal thoughts and behaviors in children and teens.

Brexanolone  

Brexanolone (sold under the brand name Zulresso) was approved by the FDA in March 2019. A derivative of allopregnanolone (a naturally produced steroid), it’s a new type of antidepressant. It appears to begin working within hours. 

Brexanolone is the first drug to have been scientifically shown to treat postpartum depression (PPD). PPD is a type of depression that can set in following childbirth. It often presents with symptoms such as anxiety, mood swings, and difficulty sleeping.

According to the Centers for Disease Control and Prevention (CDC), 1 in every 8 American women experience PPD. 

How does it work?

Brexanolone modulates the function of the brain’s gamma-aminobutyric acid type A (GABA-A) receptors. GABA receptors may have an important function in altering vulnerability to anxiety and depression. How exactly brexanolone exerts its antidepressant effects isn’t known.

Side effects

Common side effects of brexanolone include:

  • Dizziness
  • Sedation
  • Dry mouth
  • Loss of consciousness
  • Hot flushes

Esketamine  

Esketamine (sold under the brand name Spravato) was approved by the FDA in March 2019. 

Esketamine is in a new class of antidepressants, based on the pain medication and general anesthetic ketamine, a drug that has been used clinically for decades.

It’s the first ketamine-based antidepressant for people experiencing treatment resistant depression (TRD). TRD is depression that doesn’t get better after at least two antidepressant therapies.

Recently, the FDA also approved esketamine for people who are having suicidal thoughts or have attempted to harm themselves. Esketamine is recognized for its quick action — many people see symptoms of major depressive disorder reduced within 24 hours of the first dose. Other medications can take weeks before benefits are observed.

In both indications, esketamine is approved alongside an oral antidepressant. That means it will always be taken with another medication to treat these conditions.

How does it work?

Esketamine interacts with your body’s glutamatergic system, which is thought to create synapses (connections) in the brain.

A reduced number of synapses between brain cells has been associated with depression. It’s thought that esketamine helps create the synapses that impact depression.

One treatment with the drug appears to produce antidepressant effects within hours and lasts for a week or longer.

Side effects

Common side effects of esketamine include:

  • Sedation or lethargy
  • Dissociation
  • Dizziness
  • Nausea and vomiting
  • Anxiety
  • Numbness
  • Lower urinary tract symptoms

It may also cause a temporary increase in blood pressure.

Less common but potentially serious side effects include suicidal thoughts and behaviors. If you experience severe side effects while taking esketamine, seek emergency medical attention.

Most commonly prescribed antidepressants 

The types of antidepressants prescribed most often for depression are selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). These medications also carry black box warnings.

SSRIs

Low levels of serotonin in the brain have been associated with anxiety and depression. SSRIs prevent serotonin from moving back into the nerve endings (serotonin reuptake), boosting levels of serotonin in the brain.

Frequently prescribed SSRIs include:

SNRIs

SNRIs inhibit the reuptake of the neurotransmitters norepinephrine and serotonin.

Frequently prescribed SNRIs include:

Takeaway  

The FDA has recently approved brexanolone (Zulresso) and esketamine (Spravato) to treat depression. These new approaches for treating depression appear to offer some worthwhile advantages compared to SSRIs and SNRIs, including acting in hours as opposed to days or weeks. 

Brexanolone has been approved to treat postpartum depression. Esketamine has been approved to be used alongside oral antidepressants for treatment resistant depression and suicidal thoughts.

If you’re interested in brexanolone or esketamine, talk with your doctor to see if they’re right for you. All medications carry risk. It’s important to review all the possible side effects with your doctor.