Menu

Depression: The Latest Research

Medically Reviewed by Jennifer Casarella, MD on July 14, 2021

If you’re one of more than 17 million adults or 3.2 million teens in the United States with major depression, you may know that treatment often falls short. The latest research on this common mental health disorder, also called clinical depression, aims to help you feel better faster, and with fewer side effects.

Right now, doctors don’t have a precise way to tell which medication is best for you. That’s part of the reason that many people with depression have to try more than one drug before they feel better.

Most antidepressants, the type of drug doctors often use to treat depression, take weeks to months to work. That means a lot of time can pass before you know if the treatment helps your symptoms. And, about 30% of people don’t feel better even after trying several medications. Doctors call this treatment-resistant depression.

Because this trial-and-error process takes time -- and sometimes doesn’t work -- depression can continue to affect your ability to live your life.

Recent numbers from the National Institute of Mental Health show that depression causes major distress and life disruption for more 63% of adults and more than 70% of teens with the disorder. Depression can also lead you to think more about or to attempt suicide.

Here’s a look at what researchers are studying now and how their work may help you if you have depression.

Fast-Acting Antidepressants

Fast-acting antidepressants can work in hours to help you feel better if you have depression or suicidal thoughts. The FDA in 2019 approved the first, a nasal spray called esketamine for treatment-resistant depression. A year later the FDA approved it for depression that includes suicidal thinking.

Esketamine, which you might take with a traditional antidepressant, is made from an older medication called ketamine. Doctors first used ketamine years ago as an anesthetic, a drug used to put people to sleep.

Ketamine can also rapidly improve depression but can cause serious side effects. These include out-of-body experiences and hallucinations. Some people abuse ketamine.

Esketamine can cause similar side effects and abuse problems. However, a 2021 review of studies published in Frontiers in Neuroscience reported that its effects are usually mild to moderate and don’t last long.

Scientists think esketamine improves depression by raising levels of glutamate, a chemical that helps brain cells communicate. Researchers are studying a number of newer agents that work on glutamate or on GABA, another of your brain’s chemical messengers. Scientists hope they may have fewer side effects than current options.

The FDA has given breakthrough therapy status to several experimental fast-acting antidepressants. The agency gives this status to speed development of drugs that may be able to outperform available treatments for serious conditions like depression.

More Exact Antidepressant Selection

Right now, doctors rely mostly on guesswork to choose your antidepressant. The latest research may give them tools that can help them pick the best treatment for individuals. Tests and tools that may cut down on trial and error in antidepressant treatment include:

Blood tests. Recent studies show blood tests that measure levels of certain proteins can predict whether particular antidepressants are likely to relieve your symptoms.

Gene tests. Tests for certain genes and how they affect your body’s response to specific drugs may help guide your doctor to the best treatment for you. In one recent study, people who took a 10-gene test to help direct treatment choice got better more often than those whose treatment was chosen without the test.

Brain imaging. Researchers are testing SPECT (single positron emission computed tomography) and PET (positron emission tomography) to see if these imaging tools can help doctors choose the right drug for you. They show activity in different areas of your brain.

A recent review of studies found that using PET to look at how the brain uses glucose, or sugar, could help predict whether an antidepressant would improve a person’s depression.

Artificial intelligence (AI) that reads brain scans. Some scientists hope to treat depression with AI programs that can find patterns in EEG (electroencephalogram) scans. These scans measure your brain’s electrical activity. A 2020 Nature Biotechnology study found that an AI program could use a person’s EEG data to predict whether the most common type of antidepressant would work for them.

Causes of Depression

New knowledge about the causes of depression could open the door to new treatments. These biological processes may play a role:

Inflammation.  Inflammation is your body’s natural defense against infections and injury. But when it happens when it shouldn’t or gets out of control it can lead to or worsen many different diseases. Depression is one of them, according to the latest research.

In the largest-ever study of depression and inflammation, published in 2021 in the American Journal of Psychiatry, scientists confirmed the link between the two. They found people with depression had more inflammation than those without the mental health disorder. This was true even after scientists accounted for other factors involved in depression.

This means that medications that lower inflammation may be helpful add-ons to antidepressant treatment. Lifestyle changes that can reduce inflammation, such as exercise and a healthy diet, may also help improve symptoms of depression.

The gut-brain connection. You’ve got trillions of bacteria and microorganisms, or microbes, in your gut. Some are helpful and some can be harmful. When the balance isn’t right, it can add to health problems, including depression and inflammation.

Some of the latest research has found that probiotics, which can give you a better balance of gut microbes, may also ease symptoms of depression. Probiotics are living bacteria found in fermented foods like yogurt or in supplements. They have few side effects.

Scientists need to learn more about how probiotics work in people with depression. Some studies find they work best when you use them along with antidepressant drugs. Research also suggests different strains, or types, of probiotics may help with different symptoms of depression.

In the meantime, it’s probably safe to try a probiotic for a month to see if it improves your mood. Just don’t stop any of your prescribed medications without the OK from your doctor.

WebMD Medical Reference

Sources

SOURCES:

National Institute of Mental Health: “Major Depression,” “Mental Health Medications.”

UT Southwestern Medical Center: “Breakthroughs in depression research lead to more effective treatments.”

British Medical Bulletin: “Managing inadequate antidepressant response in depressive illness.”

Psychiatry and Clinical Neurosciences: “Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective.”

Chronic Stress: “Emerging therapeutics based on the amino acid neurotransmitter system: an update on the pharmaceutical pipeline for mood disorders.”

Neuroscience Bulletin: “Major depressive disorder: Advances in neuroscience research and translational applications.”

Frontiers in Neuroscience: “Repurposing ketamine in depression and related disorders: Can this enigmatic drug achieve success?” “Intranasal ketamine for depression in adults: A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials.”

Alcohol Health and Research World: “GABA and the GABAA receptor.”

Johns Hopkins Medicine: “Esketamine for Treatment-Resistant Depression,” “Can Probiotics Improve Your Mood?”

Harvard Health Publishing: “Ketamine for major depression: New tool, new questions,” “Understanding acute and chronic inflammation.”

Nature Biotechnology: “An electroencephalographic signature predicts antidepressant response in major depression.”

Biogen: “Sage Therapeutics and Biogen Announce Positive Pivotal Phase 3 Results for Zuranolone, an Investigational Two-Week, Once-Daily Therapeutic Being Evaluated for Major Depressive Disorder.”

PRNewswire: “NeuroRx Initiates Pivotal Study for NRX-101, a Breakthrough Designation Therapy Targeting Suicidal Bipolar Depression.”

FDA: “Breakthrough Therapy.”

Brain, Behavior, and Immunity: “Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection.”

Psychoneuroendocrinology: “Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial.”

Journal of Psychiatric Research: “Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: A randomized clinical trial demonstrating clinical utility.”

Mayo Clinic: “SPECT Scan.”

American Journal of Psychiatry: “Using the power of a giant wisely: confirming inflammation in depression,” “Elevated C-reactive protein in patients with depression, independent of genetic, health, and psychosocial factors: results from the UL biobank.”

Medscape: “Inflammation a Core Feature of Depression.”

Harvard T.H. Chan School of Public Health: “The Nutrition Source: The Microbiome.”

Nutrients: “Exploring the role and potential of probiotics in the field of mental health: major depressive disorder.”

© 2021 WebMD, LLC. All rights reserved.