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USU researchers work to discover new treatments for depression

A wide shot of Browne as she uses a multi-pipette to fill a microplate. Dr. Caroline Browne prepares an assay to examine if the presence of HNK can raise BDNF in the body. If so, it could mean a possible new treatment for depression. (Photo by Christopher Austin)
By Christopher Austin

Researchers at Uniformed Services University (USU) led by Dr. Irwin Lucki, professor and chair of the Department of Pharmacology and Molecular Therapeutics, are working to discover drugs that could be used for individuals with treatment-resistant depression.

“Depression is the leading cause of disability from any medical illness today. We’re desperately in need of new medications to treat depression,” said Lucki. “A lot of people don’t realize that current treatments only work for half of the people they’re prescribed to, meaning there are lots of people out there that are not able to be treated by existing antidepressants.

“Depression is a tremendous problem for the military,” he continued. “Especially among deployed men and women and their families. Our interest is in discovering antidepressants that are more effective than the ones we have right now.”

The researchers are examining a product of the drug ketamine, a metabolite called hydroxynorketamine (HNK), as a possible treatment for depression. Ketamine is currently used for the treatment of depression via intravenous infusion because it works immediately. Ketamine may also work to reduce suicidal behavior. The treatment requires patients to visit a clinical setting and be monitored for an extended period as the drug’s initial hallucinatory effects wear off.

Alt-Text 02: A closeup of Browne’s hands as she uses a multi-pipette to fill a microplate.
Dr. Caroline Browne prepares an assay to examine if the presence of HNK can raise BDNF in the body. If so, it could mean a possible new treatment for depression. (Image credit Christopher Austin)

“With conventional antidepressants, you can go six to eight weeks before you see any effects,” said Dr. Caroline Browne, a research assistant professor in the Pharmacology department at USU. “In the treatment resistant population, there are patients who have failed multiple trials and have had no response for years. We know there’s a drug out there like ketamine that can remediate a patient’s symptoms within hours, and we need to pursue it.”

Lucki’s group is collaborating with clinical researchers led by Dr. Carlos Zarate at the National Institute of Health. Zarate’s team was one of the first to discover the antidepressant effect of ketamine. They’re now working with USU researchers to test how effective the molecule HNK can be at treating depression in subjects. The end goal is to discover a drug that can be administered to patients without the hallucinogenic effects, and that works much faster than current antidepressant treatments.

Most importantly, researchers want to isolate the antidepressant components of ketamine and learn its mechanism of action. Metabolites of ketamine, like HNK, might be used to safely treat patients who are resistant to current treatments without producing hallucinations.

Researchers are also examining buprenorphine as an antidepressant. The drug is already used to treat drug addiction and pain, but healthcare providers noticed an antidepressant effect in many patients who were administered the drug. This has now led to several researchers around the world, including Lucki’s group, looking into its possible use for treating depression.

Caroline Browne points at a graph on a laptop screen that’s on a countertop in a laboratory.
Dr. Caroline Browne, assistant professor in the Department of Pharmacology and  Molecular Therapeutics at USU, goes over the results of an experiment conducted to see how hydroxynorketamine (HNK), a byproduct of the human body processing ketamine, impacts the presence of brain derived neurotropic factor (BDNF), a protein that’s linked with antidepressant response. (Image credit Christopher Austin)

“I remember one individual I encountered when we were at the University of Pennsylvania. A patient was put on buprenorphine after 20 years without alleviation of symptoms, and it (buprenorphine) worked quickly,” Browne said. “We know this drug works for many people, but it is not perfect. It may be the best we can do for treatment resistant patients until we find something better.”

This research, if successful, could lead to not only relief for millions suffering from untreated depression, but possibly streamline treatment methods into safer forms.

“Although there are antidepressants that can help some people now, it doesn’t mean we can’t improve them or make them better,” Browne said. “We want patients that are treatment resistant to walk out of the clinic and feel better right away. It may be possible to give them their life back.”