Veterans’ Study Shows Effectiveness of Ketamine Against Depression

The former ‘party drug’ ketamine has gotten some good press recently, with clinical trials suggesting it might be a powerful and fast-acting antidepressant.

Now, one of the first “real-world” studies of ketamine against depression appears to support those findings.

Researchers at the University of Michigan and the VA Ann Arbor Healthcare System say that almost half of 215 veterans who’d been suffering severe, treatment-resistant depression benefited from six weeks of ketamine infusions.

“It’s not a silver bullet,” stressed study lead author Dr. Paul Pfeiffer. “But when we see these patients in our clinic, who have been through every treatment available and nothing has worked, to have even a quarter achieve a significant measurable response is very good. We routinely get thanked for making a difference in their lives.”

Pfeiffer led the study with Dr. Avinash Hosanagar. Both are faculty at the U-M Medical School department of psychiatry, and both treat patients in the VA Ann Arbor Healthcare System.

The veterans involved in the new study were selected because they’d all tried and failed multiple treatments to curb their severe depression. Many had other mental health issues, such as post-traumatic stress disorder (PTSD), anxiety or a history of alcohol or drug abuse.

The Michigan researchers had each of the patients receive ketamine infusions beginning in 2019 or the first nine months of 2020. Their outcomes were tracked for a year after their first infusion.

Patients received an average of 18 ketamine infusions spread out over a number of months. The first few infusions were given twice a week.

Almost half of patients did get a real boost from the therapy, seeing a meaningful drop in scores on standard tests that measure depression, the study found.

A minority of patients — 15% — fared so well that by six weeks into treatment their depression was declared to be in remission.

Initial publicity around the use ketamine for depression suggested almost instant results. But those findings from clinical trials weren’t mirrored in this “real-world” study.

“These findings ratchet down the hype about ketamine a bit, because we don’t see dramatic improvement after just one infusion, or strong response in most patients,” Pfeiffer noted in a university news release.

“The chronic nature of their conditions is not something ketamine will magically reverse, but when they do respond and feel better, and don’t have to wait as long to see an impact as they do with a traditional antidepressant, it instills a sense of hope,” he explained.

These were often tough-to-treat cases: Most had already undergone dozens of outpatient treatments (including multiple forms of standard antidepressants). Many had been admitted to inpatient psychiatric care in the year prior to their ketamine treatment, while others had undergone shock therapy treatments, the authors noted.

Receipt of any of those treatments did not seem to be related to whether or not ketamine helped, the researchers noted.

The study was published recently in the Journal of Clinical Psychiatry.

Ketamine has a decades-long history of use as an anesthetic, and it also became a popular “club drug” for illicit use.

But its success against depression has raised the drug’s profile, and the U.S. Food and Drug Administration recently approved a patented nasal spray form of ketamine called esketamine. That was not the infused version of ketamine used in the new study, however.

“It’s important to remember that ketamine is relatively new as a treatment, and there are multiple ways it can be delivered,” said Pfeiffer. “I think we’re in for an interesting decade of a changing landscape for care of treatment-resistant depression.”

More information

Find out more about the use of ketamine for depression at Harvard Health.

SOURCE: University of Michigan, news release, Feb 5, 2024