Unmet needs exist in ketamine research

Sanjay Mathew

SAN DIEGO — An expert discussed the research supporting ketamine and esketamine for treatment-resistant depression as well as what future research should focus on in a session presented at Psych Congress.

“The objective of this talk is to give issues I think are critical for clinicians to know and think about in this brave new world where we finally have a FDA-approved version of ketamine on the market and available for use,” Sanjay Mathew, MD, Marjorie Bintliff Johnson and Raleigh White Johnson, Jr. Vice Chair for Research and professor of psychiatry of psychiatric and behavioral sciences, Baylor College of Medicine, said. “Also, at the same time, we’re navigating the off-label world of IV ketamine and different forms of ketamine for a variety of indications beyond depression, including anxiety, PTSD and even substance abuse disorders. The expansion of possible indications is a really interesting development.”

In his presentation, Mathew broke down the research that led to the FDA approval of intranasal esketamine as an adjunctive treatment for treatment-resistant depression earlier this year. Ketamine, however, does not have any FDA-approved indication for psychiatry.

As a NMDA receptor channel blocker, ketamine’s antidepressant mechanisms of action is complex, according to Mathew.

In a previous study, researchers found that opioid receptor antagonism may attenuate the antidepressant effects of ketamine. Some clinical predictors or mediators of ketamine’s efficacy may include anhedonia; family history of alcohol use disorder; early, rapid response and dissociating side effects; early infusion-related anxiety; and hopelessness, according to the presentation.

Mathew said that more data is needed to determine other routes of administration, dose, its use in late-life depression, clinical predictors of effectiveness, sex differences, adverse effects of long-time use and its long-term efficacy and safety.

“We have a lot of unmet needs in terms of research and clinical directions. Most importantly — what do we do in the long-term, what do we do with the elderly patients, what are our dosing strategies and what do we do to identify response predictors,” he concluded. “Real world data is needed, data gathering will be critical and understanding the mechanism of action will help guide future drug development.” – by Savannah Demko

References:

Mathew, SJ. Top 5 issues clinicians should know about ketamine therapy. Presented at: Psych Congress; Oct. 3-6, 2019; San Diego.

Disclosures: Mathew reports consulting for Alkermes, Allergan, Clexio Biosciences, Intracellular Therapies, Janssen, Perception Neurosciences and Sage Therapeutics, as well as grant/research support from Biohaven and VistaGen Therapeutics.