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Spotlight on Clinical Research

Research May Lead to New Treatments for Depression
Gerard Sanacora, PhD, MD
Professor of Psychiatry and Director, Yale Depression Research Program
Many of the drug classes we use to treat mental illness were initially developed almost 50 years ago. This is especially true of depression. Some anti-depressants that are still used today were developed in the 1960s and most of the newer drugs that have since been developed target the same pathways as the older drugs.

About 60 percent of patients suffering from depression end up doing very well with the currently available medications, but they sometimes have to try up to four different drugs, which could take a year or longer. “We can help a lot of people with our current treatments, but there are still 40 percent of the patients seeking treatment who are not getting a huge benefit. We’ll never be able to help them if we continue to design new medications that work the same way as the old ones,” said Dr. Gerard Sanacora, a Yale psychiatrist who treat and conducts research on depression.

Dr. Sanacora and other Yale doctors have been studying depression with the aim of understanding the causes of this disease and how it affects the brain. Yale is at the forefront of research on depression, conducting research that has led to potential new treatments that target the pathways of a different neurotransmitter than existing medications.

Some of these studies have looked at ketamine, traditionally used as a general anesthetic for children and also used as a recreational drug known as “Special K.” In research studies, ketamine has shown a very rapid and dramatic effect on depression. While the results are very promising, there are still real concerns and limitations regarding the use of the drug. Doctors at Yale and other sites are conducting further studies to find out how safe it is and how well it works if given repeatedly, whether it is addictive, and the best dosage that is effective while minimizing risks.

Ketamine has helped to open the door to other drugs that work on the glutamate neurotransmitter system. Research at Yale suggests that depression may be tied to an impaired ability to clear excessive glutamate in the brain. Fortunately there is already a drug on the market that helps clear glutamate from the system. Riluzole, a drug used to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is believed to work in part by enhancing the clearance of glutamate.

In open label studies – where the researchers and patients know which treatment is being given – Riluzole appears to help many people with a variety of mental illnesses. Yale is currently enrolling depressed patients in a randomized placebo controlled study, in which neither researchers nor patients know if the drug or a placebo (a neutral substance that has no effect) is being administered. This type of rigorous testing is a normal and necessary step in the process of developing new treatments.

Yale also has several studies for other new compounds to treat depression. To find out if you are eligible to participate in a clinical trial, call Donna at 203-764-9131 or e-mail For more information on depression research at Yale, visit