Newer antidepressants: Brixanolone, esketamine, agomelatine

Antidepressants are medications that can help relieve symptoms of depression, such as fatigue and emotional numbness.

Several different types of antidepressants exist, but the most common are selective serotonin reuptake inhibitors (SSRIs).

Fluoxetine (Prozac) entered the market in 1988 As the first SSRI, and over the next 30 years, many experts considered SSRIs to be “modern” antidepressants.

In 2019, the Food and Drug Administration (FDA) approved two new antidepressants, Brixanolone And the to avoid. There has also been a renewed interest in agomelatineAn antidepressant is not currently available in the United States.

Read on to learn more about these new antidepressants, including how they compare to SSRIs, their side effects, and how to try them.

In 2019, the US Food and Drug Administration approved brexanolone (Zulresso) as the first drug specifically designed to treat moderate to severe postpartum depression (PPD).

Experts consider some SSRIs to be safe during pregnancy or breast-feeding, but these medications may not lead to much improvement. several weeks. When you have postpartum depression, symptoms not only affect your health – they can also have long-term effects on your relationship with your baby.

However, Brexanolone starts working right away. According to the two randomized clinical trials Published in 2018, this drug can significantly reduce symptoms of postpartum depression — benefits achieved when researchers followed up with participants 30 days after treatment.

Learn more about treating postpartum depression.

How it works

Brixanolone increases brain levels of the neurotransmitter gamma-aminobutyric acid (GABA).

In short, GABA dampens chemical activity in neurons, almost like a dimmer switch for specific cells.

Scientists aren’t sure exactly how brexanolone treats PPD symptoms, but one theory It is suggested that with PPD, GABA levels do not recover quickly enough from pregnancy to manage stress. Basically, cortisol hormones rise unchecked, which contributes to depressive symptoms. Brexanolone, then, may offer a “reset” by restoring your GABA levels.

You receive this medicine as a one-time intravenous (IV) treatment throughout the cycle two and a half days. You will remain in your healthcare center for the full 60 hours of treatment for observation.

Safety and side effects

Like other medicines that affect GABA levels, brexanolone can cause sedation. severely 1 in 4 people Experience of anesthesia-related side effects in the first 24 hours of treatment.

You may feel:

  • Very sleepy, even during the day
  • Unfocused and dispersible
  • Dizzy or faint

Your care team will check you every two hours for severe symptoms such as fainting. If you get serious side effects, they will stop the infusion. Symptoms associated with indoor anesthesia should cease 15 minutes After stopping the intravenous infusion.

How to get a prescription

You can only receive this treatment from approved healthcare centers, and you will need a referral from a doctor to join the treatment program.

Treatment can cost Up to $34,000, although health insurance can help offset some of the cost. Companies like Etna And the Cigna They require prior authorization, so you’ll need to make sure your insurance provider covers the treatment before checking into your clinic.

Also keep in mind that most insurance companies only cover one round of treatment, as research has yet to explore the potential benefits of additional rounds of treatment.

The company that makes brexanolone also offers several products Financial Assistance Programswhich might be worthwhile if the price makes it so unattainable.

Esketamine (Spravato) is a chemical cousin of the drug ketamine. The U.S. Food and Drug Administration (FDA) approved esketamine in 2019 to treat treatment-resistant depression, or depression that persists after trying at least two different antidepressant treatments.

During clinical trials, doctors gave participants esketamine nasal spray or a placebo spray. All participants also took an oral antidepressant they had not tried before. Compared to people who took oral antidepressants and used a placebo spray, those who used esketamine spray reported Greater symptom relief And the Longer, symptom-free periods.

How it works

Esketamine kicks off a Chemical chain reaction It eventually raises levels of brain-derived neurotrophic factor (BDNF). BDNF helps your neurons form new connections, which in turn enables you to form memories, learn new information, and develop different habits.

Depression usually involves low levels of BDNF, and your brain may have trouble adjusting to the changes. Esketamine helps restore BDNF levels, along with the overall plasticity of the brain.

As with brexanolone, you should take esketamine in the presence of a healthcare professional. Your doctor or doctor will give you a dose between 56-84 milligrams (mg)that you spray in your nose. Then relax on a chair for two hours. Your care team will monitor your blood pressure and heart rate during this time.

This medication works quickly, with many people noticing relief right away. The treatment requires multiple sessions, usually twice a week for the first 28 days and then spaced out over time. Effects usually last until the next dose.

Safety and side effects

In clinical trials, participants tended to report mild to moderate side effects. You may feel drowsy, dizzy, or “out” a little during the treatment session. These side effects often go away Within 90 minutes after taking your dose.

In rare cases, people have reported more serious side effects such as:

  • vomiting
  • Anxiety and confusion
  • Worsening of depression or suicidal thoughts

Esketamine can also cause a significant increase in blood pressure during the treatment session, which is why you will need to be monitored for 2 hours. If you have high blood pressure or any other vascular condition, be sure to tell your doctor before receiving treatment.

How to get a prescription

You can only receive this treatment at an approved health care center, so you will need to ask your doctor or psychiatrist if you want to try esketamine.

The course of treatment depends instead on the severity of your symptoms – and how much you can pay. From 2021For example, a standard 56-mg dose of esketamine costs $590, and a large 84-mg dose costs $885.

The first month of treatment is often the most expensive as treatment guidelines recommend treatment twice a week for the first month. The first month can cost anywhere between $4,800 and $6,800.

To date, there are no official guidelines establishing the ideal duration of treatment.

according to The company that produces SpravatoSome insurance programs cover most esketamine costs. You’ll only need to pay $10 in co-payments per session until you reach the benefits cap of $7,150 per year.

Agomelatine (Valdoxan), an oral antidepressant, has been available in some other countries since 2009, although you cannot obtain this medication in the United States.

You are taking agomelatine as a file 25 mg tablets Once a day at bedtime. If your depression symptoms do not respond, your doctor may increase your dose to 50 mg daily.

May be agomelatine special benefit For depression that:

How it works

agomelatine has two main effects In your mind. It increases the activity of the neurotransmitter melatonin receptors, which helps you fall asleep. It also reduces the activity of specific serotonin receptors and helps increase dopamine and norepinephrine in the frontal cortex.

Increasing levels of melatonin can improve sleep-related problems. in the small Study 2018 Involving 24 young adults, the researchers found that the more agomelatine altered the participants’ circadian rhythms, the better their depressive symptoms improved.

Experts don’t yet know exactly how the decrease in serotonin fits into the picture.

That said, seniors Animal Research from 2014 It is suggested that boosting melatonin and simultaneously reducing serotonin binding to receptors may help protect newly created neurons by protecting them from damage from chronic stress.

Safety and side effects

Agomelatine may cause:

  • Vomiting and nausea
  • Constipation, stomach pain and diarrhea
  • drowsiness or difficulty sleeping
  • headache

But many people experience only mild side effects while taking agomelatine, which may partly explain the renewed interest in this antidepressant.

After all, if you are not experiencing severe side effects, you will likely feel more inclined to continue taking the medication.

How does agomelatine compare

a 2018 review Including 522 trials with a total of 116,477 participants comparing 21 antidepressants.

When the review authors looked at dropout rates due specifically to adverse reactions, they discovered that all of the included antidepressants had a higher dropout rate than placebo — except for agomelatine.

Incidentally, researchers also listed agomelatine as one of the seven most effective antidepressants among those studied.

With many antidepressants, you may experience flu-like symptoms if you suddenly stop taking the medication. This phenomenon, called discontinuation syndrome, does not occur with agomelatine. You can easily stop until Long-term use of agomelatine.

So, you might be wondering: If this drug works so well, what’s holding back approval in the United States?

Agomelatine has the potential to cause one very severe side effect: liver toxicity. The drug raises levels of amino acids in the liver called transaminases, causing liver damage up to 4.6% of the people who take it. People taking this medicine need to have their liver function tested Weeks 3, 6, 12 and 24 of treatment.

Other antidepressants can have a similar effect on the liver, but in Much lower rates:

  • placebo: 2.1%
  • Escitalopram (Lexapro): 1.4%
  • Paroxetine (Paxil): 0.6%
  • Fluoxetine (Prozac): 0.4%

How to get a prescription

Currently, you cannot obtain a prescription for agomelatine in the United States or Canada, as regulators have deemed the risk of liver injury too high to allow the drug to be marketed.

It is likely that agomelatine will become more widely available in the future if researchers identify a way to reduce the risk of hepatotoxicity.

Doctors in Europe and Australia He may prescribe this medication.

Brixanolone and esketamine appear to have the greatest benefit in postpartum depression and treatment-resistant depression, respectively. These drugs also come at a high price that can make them more difficult to access.

Agomelatine can effectively treat a wide range of depression subtypes. But it also carries a risk of hepatotoxicity, and is not approved for use in the United States.

In short, these medications likely won’t replace SSRIs as the first line of treatment for other types of depression anytime soon. However, their presence opens possibilities for future advances in the treatment of depression.


Emily Swim is a freelance health writer and editor specializing in psychology. She received a BA in English from Kenyon College and an MA in writing from California College of the Arts. In 2021, she was certified by the Board of Editors in Life Sciences (BELS). You can find more of her work at GoodTherapy, Verywell, Investopedia, Vox, and Insider. find it on Twitter And the LinkedIn.