Spotlight On: Major Depressive Disorder

Rates of depression are on the rise, especially among teens and young adults. Almost 1 in 10 Americans over age 12 has had at least one episode of major depression in the last year.  Not everyone who struggles with depression gets the help they need. One reason is that help is hard to find. Many parts of the United States face a severe shortage of psychiatrists, especially lower income and minority communities. And about one-third of people who do get treatment aren’t able to get relief from their symptoms.


Did You Know?

An important discovery in the brain has led to the approval of the first medication designed for postpartum depression.


But not all depression trends are negative. New findings in the research world should give hope to anyone who has tried current treatments without success. Researchers have made great progress in understanding the genetics and biology of depression.  “Together, this work for the first time is putting depression research on an equal scientific footing with other medical disorders,” says John Krystal, MD, who is the Robert L. McNeil, Jr. Professor of Translational Research at the Yale School of Medicine in New Haven, CT.  What researchers have discovered has led to new depression treatments that work much faster. These new therapies could offer real alternatives to people who don’t find relief with antidepressants. Understanding depression as a disease might also help to break through some of the stigma that has long surrounded the condition.


These are just some of the latest trends and highlights in depression research.

Fast-Acting Depression Relief 

Antidepressants like selective serotonin reuptake inhibitors (SSRIs) can be very effective for depression, but they take a long time to start working. For anyone with severe depression symptoms, the 2 months it sometimes takes for an SSRI to relieve symptoms can be an agonizing wait. “The big thing that’s happened over the last 2 decades is the idea that depression can be treated rapidly,” says Nolan Williams, MD, associate professor of psychiatry and behavioral sciences at Stanford University in Stanford, CA. “What that means is we can get you well in days, not months.” He points to new drugs like ketamine that treat depression through a different pathway. Ketamine enhances the production of a chemical messenger in the brain called glutamate. “You might say [glutamate is the] main information highway of the brain,” says Krystal, who is also chair of the Department of Psychiatry at Yale University.


Brain imaging studies done on people with depression revealed they have less communication between nerve cells, Krystal says. Glutamate helps nerve cells “talk” to one another.  Ketamine was used for decades as an anesthetic and more recently as a club drug. In depression, it works to quickly restore the connections between nerve cells. In 2019, the FDA approved a nasal spray version of ketamine, called esketamine (Spravato), to treat people whose depression hasn’t improved on two different antidepressants.  Psychedelic drugs like psilocybin and MDMA (ecstasy) work in a similar way to ketamine – by making new connections in the brain. These drugs also show promise for treatment-resistant depression. In studies, psilocybin worked quickly to relieve depression and MDMA showed promise for treating posttraumatic stress disorder (PTSD), Krystal says. He expects the FDA to review these psychedelics in the next year or so.

The First Drug for Postpartum Depression

Depression is already more common in women than men, and the risk goes up after childbirth. Up to 1 in 7 new moms develop postpartum depression. In the past, the main treatments were talk therapy and antidepressants. But an important discovery in the brain has led to the approval of the first medication designed for postpartum depression. Studies of very depressed people have found a drop in gamma-aminobutyric acid (GABA), another chemical that helps brain cells send messages back and forth. Brexanolone (Zulresso) acts on this system to treat postpartum depression. When you get it through an IV, it works quickly to relieve depression with few side effects.

Lower Inflammation, Treat Depression

Another area of interest in depression research centers on inflammation. It’s a factor in many chronic conditions like Alzheimer’s, heart disease, and asthma. Inflammation also plays a role in depression. “Approximately one-third of depressed patients have prominent inflammation in their body and/or brain,” says Krystal. There’s a growing interest in using anti-inflammatory drugs to manage depression in people who haven’t responded to standard antidepressants.

Brain Stimulation

Medication isn’t the only way to manage depression. Another approach to treatment-resistant depression targets the brain more directly.  Neuromodulation is a noninvasive treatment that stimulates nerve cells with magnetic fields to relieve depression symptoms. In 2022, the FDA cleared a system that Williams developed, called the SAINT neuromodulation system. He says it should be available in hospitals in 2024.


One advantage to neuromodulation is that it doesn’t cause drug interactions like some antidepressants can. And it can be used in people with a wide range of depression severity – from those who have only failed on one medication all the way up to people with the most severe treatment-resistant depression.

The Teletherapy Trend

During the pandemic, talk therapy moved from the clinic into people’s homes. In the time of COVID-19, virtual therapy was meant to prevent the spread of infection, but it has caught on. Doing therapy sessions over a computer or phone can be just as effective as having them in person, but only if people complete all their sessions, which not everyone does. “Still, this is an important growing area of research that may make treatment more accessible,” Krystal says.



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