A study published by Columbia psychiatry researchers has shown for the first time that in mouse models a pharmaceutical agent can provide protection against stress. A single low-dose injection of ketamine was found to protect the mice against stress, a risk factor for such psychiatric disorders as post-traumatic stress disorder (PTSD) and depression. The researchers used mouse models to simulate stress-induced psychiatric disorders and found that giving ketamine before a stressor protected the mice against depressive behavior. Fluoxetine, a common antidepressant, which the researchers used as a control, did not protect against stress. The proof-of-concept study was published online in May in Biological Psychiatry.
While ketamine remains in the body for only a few hours, the protective effect observed in the mice lasted at least four weeks, suggesting a self-maintaining drug-induced resilience. Additionally, when the researchers compared the protective effect of ketamine with its effectiveness as an antidepressant (i.e., given after stress), they found the protective effect was far more robust than the antidepressant effect.
If this research translates to humans ketamine could be used as a prophylactic against stress-induced psychiatric disorders.
“It’s not intuitive to think that giving ketamine before introducing a stressor would protect against stress, but from our own work over the last decade, and research in the field, we had a strong suspicion that we might be able to use ketamine prophylactically,” says Christine Ann Denny, PhD, senior author of the study and assistant professor of clinical neurobiology in psychiatry.
“If this research translates to humans,” adds first author Rebecca Brachman, PhD, “ketamine could be used as a prophylactic against stress-induced psychiatric disorders, a use of pharmacotherapy not even considered previously.”
The title of the paper is, “Ketamine as a prophylactic against stress-induced depressive-like behavior.” The other study authors are Josephine McGowan, Jennifer Perusini, Sean Lim, Thu Ha Pham, Charlene Faye, Alain Gardier, Indira Mendez-David, Denis David, and René Hen.
Drs. David and Hen are consultants for Lundbeck, Roche and Servier. The other authors report no biomedical financial interests or potential conflicts of interest.
The study was funded by the National Institute of Child Health and Human Development grant T32HD07430 (Dr. Brachman); a Lundbeck grant (Dr. David); an R37 MH068542, R01 AG043688, and a Hope for Depression Research Foundation grant (Dr. Hen); a National Institutes of Health DP5 OD017908-01, a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation, and New York Stem Cell Science N13S-006 (Dr. Denny).
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