UC San Diego conducts first large-scale study on ketamine as an antidepressant

Originally published in the La Jolla Village News.

Since its introduction in 1962, ketamine, often recognized as an illicit hallucinogenic or dissociative drug, has been used in various medical treatments. Researchers from the University of California San Diego and the Skaggs School of Pharmaceutical Sciences recently conducted the first large-scale study examining the drug's benefits in treating depression.

Utilizing the FDA's Adverse Effect Reporting System (FAERS), a voluntary database collection system set up in 2004, the researchers formulated data on side effects associated with clinical trials of the drug as a treatment for pain. Although the effects of ketamine are known, most of the information provided was from secondhand information or small studies of under 100 patients.

Dr. Ruben Abagyan, Ph.D. professor of pharmacy at UC San Diego, and pharmacy students Isaac Cohen, Tigran Makunts, and Rabia Atayee, PharmD, associate professor of clinical pharmacy, all at Skaggs School of Pharmacy, weeded through approximately 41,000 cases to collect their data. They then applied a mathematical algorithm to look for statistically significant differences in reported depression symptoms for each patient.

"We looked at records regarding the marketing of adverse effects of the drug as a treatment for pain," said Abagyan. "While the small-scale clinical trials presented information that made the drug appear safe for the market, even though it was approved, the post-market reporting system led us to believe otherwise."

Adverse effects in the pain treatment also revealed that most treated reported the lack of common depression as a side effect. One property of ketamine that is suitable for treating depression is its quick onset. The drug, often used as an anesthetic, begins to work instantaneously. This vastly differs from current antidepressants on the market, which usually take weeks to reach significant levels in a patient's body.

"Current FDA-approved treatments for depression fail for millions of people because they don't work or don't work fast enough," said Abagyan. "This study extends small-scale clinical evidence that ketamine can be used to alleviate depression and provides needed solid statistical support for wider clinical applications and possibly large-scale clinical trials."

Abagyan noted that a drug with a quick onset is paramount in cases where a patient may be dealing with suicidal depression.

"The real mechanism of ketamine works is still unknown," Abagyan added. "We have some hypotheses but no real proof. We can study the drug with many controls. For instance, if we were to inject some into a patient's neck or vocal cords, it could have two different effects."

This study found that depression symptoms in those taking ketamine dropped by 50 percent. This was with an error margin of less than 2 percent compared to patients who took other drug combinations for pain. Also, those treated with ketamine reported a loss of opioid-associated side effects, such as constipation, compared to patients receiving other pain medications.

The team continues to examine data regarding the pharmacological benefits of this drug, which is listed as a Schedule III drug in the U.S.