Metabolic biomarkers steer proper use of party drug ketamine for depression

Certain metabolites can flag patients with bipolar depression for whom intravenous doses of ketamine will work best or not at all, researchers have concluded.

Medscape Medical News reports on the new biomarker discovery, which could enable mainstream use of the drug for depression, an anesthetic that has been used illegally in nightclubs for some time under the name "Special K." Ketamine has shown promise in other studies as a fast-acting treatment for depression for some patients, and Johnson & Johnson ($JNJ) is testing a nasal spray version of the drug called esketamine, which has advanced to midstage clinical trials after generating encouraging early results. Several other ketamine-related programs are also underway that rely on subanesthetic doses of the therapy, with researchers looking for a low dose that can treat the depression without the illicit responses that made it a party drug. 

While the results of this latest study are preliminary, the research team hopes the data eventually leads to a regular blood test that can screen out depressive patients for whom ketamine will work best or not at all. Some patients gain real benefits, but others face major side effects, so it would be good to preemptively figure out who those patients are, study co-author Michael Goldberg, an anesthesiologist from Cooper University Health Care in Camden, NJ, told Medscape.

"It's not ethical to put everyone [with depression] on ketamine because it has risks," he explained to the publication. "Hallucinations are common and may require other medications to counteract."

The researchers presented their findings recently at the American Society of Anesthesiologists 2013 Annual Meeting, Medscape noted.

Their work focused on blood samples from 22 patients suffering from bipolar disorder and depression, both before and after they received a small dose of ketamine or a placebo. Many patients also received lithium as a mood stabilizer. For this group, patients who didn't respond to ketamine generated variations in 18 metabolites compared to those for whom ketamine worked well. Patients treated with the mood stabilizer valproate produced similar results on a smaller scale, the researchers said. Interestingly, patients who didn't respond to ketamine and weren't also treated with mood stabilizer generated much larger amounts of the amino acid D-serine.

To pursue their work, the researchers used a blood test that relied on pharmacometabolomics, which measures metabolic patterns, the story noted. The initial pharmacometabolomic process took a lot of time and wasn't exactly cheap, study co-author Irving Wainer from the National Institute on Aging's Intramural Research Program in Baltimore, MD, is quoted as saying. Still, they'll use the same technique in a planned study of patients with post-traumatic stress disorder after they receive a ketamine infusion. Also, future tests will more narrowly focus on 5 or 6 metabolites, Wainer told Medscape. They'll also tinker with the blood test in a bid to produce more rapid results on-site.

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