Major depressive disorder (MDD) affects nearly 10% of Americans at any given time, and as many as 20% will experience symptoms at some point in their lives.
While antidepressants are the most common treatment, they don’t work for about 30% of people with MDD.
For those who don’t respond to standard medications, treatment options can be limited and frustrating.
Ketamine, originally developed as an anesthetic, has emerged in recent years as a powerful, fast-acting antidepressant. When given in low doses, ketamine can relieve depression symptoms within hours—even in people who haven’t responded to other treatments. But the relief it provides usually lasts only up to a week.
To keep symptoms away, patients often need repeated doses, which can increase the risk of side effects like dissociation, and even raise concerns about addiction and relapse after stopping treatment.
Now, a groundbreaking study published in Science suggests that it may be possible to extend the antidepressant effects of a single dose of ketamine for much longer—up to two months. The research, led by Dr. Zhenzhong Ma from Vanderbilt University, opens the door to the possibility of using ketamine in a way that avoids frequent dosing and reduces long-term risks.
The study was led by two teams of scientists: Lisa Monteggia, director of the Vanderbilt Brain Institute, and Ege Kavalali, chair of the Department of Pharmacology. They focused on a key pathway in the brain called ERK, which helps support the growth and strength of connections between brain cells—a process known as synaptic plasticity.
This pathway is essential for how ketamine relieves depression so quickly. Scientists already knew that ketamine’s short-term effects depend on this pathway, but Ma and his team asked: What if we could keep this pathway active for longer?
To test this idea, they used a compound called BCI, which blocks a protein that normally turns off the ERK pathway. By keeping ERK activity high, they were able to extend the antidepressant effect of ketamine in lab studies for up to two months.
This result is significant because it shows a new way to make a single dose of ketamine work much longer than previously thought possible. While BCI itself may not be ready for use in human patients—due to limitations in how it works in the body—the study gives scientists a clear proof of concept.
It demonstrates that targeting the right signaling pathways inside brain cells could dramatically improve how we use fast-acting antidepressants like ketamine.
Monteggia explained that the work shows ketamine’s action can be sustained by enhancing specific biological processes within the brain.
This could lead to a new generation of treatments that combine ketamine with drugs designed to boost and maintain its effects—possibly reducing the need for repeated ketamine infusions and making treatment safer and more manageable.
For patients living with treatment-resistant depression, this research offers hope for better, longer-lasting relief. It also paves the way for future studies that aim to identify safer and more precise drugs that can extend ketamine’s benefits without increasing side effects.
In short, this study is an important step forward in depression treatment. If researchers can find a way to translate these findings into a safe therapy for people, it could dramatically reduce the burden of care for millions and improve quality of life for those with severe, hard-to-treat depression.
If you care about depression, please read studies about how dairy foods may influence depression risk, and B vitamins could help prevent depression and anxiety.
For more information about mental health, please see recent studies that ultra-processed foods may make you feel depressed, and extra-virgin olive oil could reduce depression symptoms.
The research findings can be found in Science.
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