healthHealth and Medicine

FDA Approves New Fast-Acting Ketamine-Derived Antidepressant Spray


Ben Taub

Freelance Writer

clockMar 7 2019, 16:02 UTC

Esketamine is a derivative of Ketamine, and is aimed at those who have previously failed to respond to conventional antidepressants. Image: grey_and/Shutterstock

A nasal spray that could alleviate symptoms of depression in just a few hours has been approved by the US Food and Drug Administration (FDA) – though the decision has attracted its share of criticism and controversy. The new drug, called esketamine, is a molecular variation of ketamine, which is already being used as an anesthetic, an antidepressant, and a party drug.

Esketamine will be sold as a spray called Spravato and is intended for patients with treatment-resistant depression, meaning they have failed to respond to at least two other types of antidepressant. Because of ketamine’s mind-altering effects and high potential for abuse, patients will be required to take Esketamine in a doctor’s office or clinic and remain under medical supervision for two hours after administration.


Most people with a diagnosis of depression are prescribed selective serotonin reuptake inhibitors (SSRIs) such as Prozac. These ensure that neurons have access to an increased amount of the neurotransmitter serotonin, which is a key emotional regulator. However, it is thought that around one-third of people with major depressive disorder (MDD) do not respond to conventional medications for the condition, which is why researchers are hunting for alternative treatments.

Recent studies have highlighted the potential of psilocybin – the active compound in magic mushrooms – to tackle depression, though much more research is needed before its safety and efficacy can be confirmed. Similarly, ketamine has been found to aid those suffering from treatment-resistant depression, though its mechanism of action is not fully understood, hence the apprehension from some quarters around the FDA’s decision.

Previous clinical trials have shown that ketamine alleviates depression in up to 70 percent of participants, with the effects becoming noticeable in as little as two hours and lasting for up to two weeks. One study even found that it significantly reduces suicidal thoughts in as little as 24 hours.

Ketamine is already being used as an intravenous antidepressant in private clinics worldwide, although studies have shown that it is just as effective when administered nasally. Yet in spite of this, critics have pointed out that there is a lack of evidence for the efficacy of Spravato, especially when considering that the FDA decided to approve the drug on the basis of just a single trial. In most cases, a minimum of two successful trials is necessary before it approves a drug.


Ketamine’s depression-busting properties are thought to be caused by its ability to block N-methyl-d-aspartate (NMDA) receptors in the brain, which interact with the neurotransmitter glutamate. However, the drug’s full cascade of effects has still not been revealed, which is why there is still so much apprehension around its use as a medication.

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