The animal research behind the new nasal spray depression treatment

Or, our tax dollars at work!

Last week, the FDA approved a new drug for treatment-resistant depression (TRD). The nasal spray version of the drug ketamine, called Spravato (esketamine), is a newly-approved, fast-acting drug, available only with a doctor’s prescription, that could help millions.

Did you know that a wide range of nonhuman animal research in many different species contributed to the development of esketamine as an anti-depressant? This use was not the original intended purpose of ketamine, which for decades has been used as an anesthetic in both animals and humans. The new use for ketamine underscores the “long game” aspects of science – developments and discoveries can take decades, and can sometimes arise from basic research questions which lead to real world applications that improve the quality of life for millions of people.


Here, a timeline of just some of the animal-based research that led to the new ketamine drug for depression:

  • 1967: A study in monkeys established the safety of ketamine as an anesthetic
  • 1968: A study in cats identified the neuronal mechanisms of anesthesia induced by ketamine
  • 1980s: Studies in rodents, frogs, and other animals determined that ketamine acted as a NMDA antagonist (see here and here for just a few examples)
  • 1990s: Rodent studies identified the class of receptors (called NMDA receptors) affected in major depression, and as the site where antidepressant treatments act
  • Early 2000s: Studies in rats showed that a single dose of ketamine reduces depressive-like behaviors, and studies in mice further demonstrated the anti-depressive effects of ketamine
  • Mid-to-late 2000s: Studies in mice identified cellular mechanisms underlying the antidepressant effects of ketamine; research with chicks demonstrated the efficacy of ketamine in reducing depressive behaviors, paralleling early clinical data
  • 2010s: Research with monkeys demonstrated that subanesthetic doses of ketamine enhance serotonin in the brain, and that a single administration of esketamine reduces dopamine receptor binding.

Speaking of Research commends the scientists who conducted sound, rigorous, and ethical animal research over the past 50 years that collectively led to this novel treatment for TRD. Considering that:

  • Over 16 million adults in the U.S. suffer from major depression – that’s more than the combined populations of Massachusetts, Connecticut, Rhode Island, Vermont, New Hampshire, and Maine – or, essentially, all of New England;
  • Anywhere from 30-50% of those patients are diagnosed with TRD – or, between 4.8 and 8 million people; and
  • TRD costs $12-19,000 per patient per year in US, an annual cost of $29-48 billion – which is more than the individual annual budgets for the U.S. Departments of State, Justice, Homeland Security, Transportation, and many others;

This body of research – funded in part by the National Institutes of Health (NIAAA and NIMH) and the Department of Veterans Affairs – is truly a remarkable return on investment. The invaluable benefit of an improved quality of life for millions of people cannot be overstated. Our tax dollars at work!


~Amanda M. Dettmer, PhD