Credit: Wikimedia Commons.

In the future, people who struggle with mental illness and chronic depression might be able to quickly and significantly ease their symptoms with a ketamine-based nasal spray. According to a new study, patients who were classed as being at a high risk of suicide reported feeling much better in a matter of hours. The findings mirror those reported by other clinical trials — these studies employed intravenous injections of ketamine, which are far more invasive and much more difficult to administer than nasal sprays.

Ketamine is famous for being a ‘party drug’, but traditionally its been primarily used as an anesthetic by medical practitioners and veterinarians. Most recently, study after study has found that the substance is incredibly effective at easing depression symptoms at subanesthetic doses. A study published in 2017 found that the drug caused a marked reduction in suicidal thoughts only 24 hours after the drug was administered intravenously. Now, researchers at the Janssen Research and Development (a Johnson and Johnson company) and Yale School of Medicine have also come to a similar conclusion.

The double-blind trial involved 68 participants who were randomly assigned to one of two groups, either receiving 84mg of esketamine (part of the ketamine molecule) or a placebo twice a week for four weeks. Participants in both groups also received standard treatment consisting of antidepressants, regardless of whether or not they had taken ketamine. Although ketamine and esketamine are similar insofar as they target the neurotransmitter glutamate, the latter does appear to have some crucial differences such as decreased dissociative properties —that is, when people are awake but totally detached from their surroundings— compared to ketamine. In other words, esketamine has less of a high, compared to ketamine.

Only four hours after taking the drug, the participants from the esketamine group showed a significant improvement in depression scores and decreased suicidal ideation, which lingered on for up to 25 days after the last dose, as compared to the placebo.

Most antidepressants take four to six before they become fully effective. That’s a long window of time in which the patient may be tormented by suicidal thoughts, so having a drug that can improve the mood of some of the hardest cases in mere hours is a godsend — literally the difference between life and death. Esketamine could be an important treatment to bridge the gap in time that exists from the delayed effect of most common antidepressants.

Another reason this study is so exciting is that the researchers are from a private drug company, which means it’s very likely, given the positive results, that the nasal spray formula could one day become a marketable product. Compared to intravenous injections, nasal sprays are much easier and quicker to administer.

First developed in the 1960s, ketamine has recently seen a revival in a therapeutic setting after decades of being notorious as a party drug. Scientists say the drug “blew the doors off what we thought we knew about depression treatment.” One 2013 study involving 73 participants found ketamine relieved depression symptoms in 64% of patients who had tried three or more other medications with unsuccessful results — all in less than 24 hours. Other studies have reached similar conclusions. “Feeling better faster, getting the mood to improve faster — that’s why ketamine is very promising,” said Alan Manevitz, MD.

This was a phase 2 clinical trial, however, meaning esketamine must still go through a phase 3 study before possible FDA approval. For instance, one very important thing that the researchers are concerned about is esketamine’s potential for abuse. Researchers will have to monitor craving and potential ketamine use from other sources.

In the United States and the UK, some doctors are administering ketamine to patients suffering from severe depression. However, this is done only in some private clinics and the treatment’s cost is completely supported by the patient.

The findings were reported in the American Journal of Psychology (AJP). 

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