Ketamine nasal spray rapidly relieves depression and suicidal thoughts, finds trial

Significant improvement in patients at imminent risk of suicide within hours

Further trials must find a balance between making treatment available and protecting the public from an ‘epidemic of misuse’

People with serious mental illness could one day be offered a nasal spray of ketamine after a clinical trial showed the drug can rapidly tackle bouts of severe depression and suicidal thoughts.

In just a matter of hours, doctors, and the patients themselves, measured a significant improvement in symptoms of patients classed as being at high risk of suicide.

The trial of antidepressant esketamine by Yale University researchers and the manufacturer, Janssen, suggests it could be effective in bridging the gap where conventional antidepressants take weeks to be fully effective.

Esketamine, a part of the mind-altering ketamine molecule, has been designated a “breakthrough therapy” by the US Food and Drug Administration after early trials showed it could help patients “at imminent risk” of suicide.

This status allows the drug’s development process to be sped up to so it can become available in the clinic, and the results from phase two trials reported in the American Journal of Psychology (AJP) today still appear promising.

Previous trials with intravenously injected ketamine have already found benefits, but a nasal spray is much easier to administer in a controlled dose.

For the study, 68 patients at imminent suicide risk, who were also receiving treatment with conventional antidepressants, were randomly assigned to receive either esketamine or a placebo nasal spray twice a week for four weeks.

The trial was “double blind”, so neither patients nor doctors knew which treatment was being given, and found significant improvements in the ketamine group’s symptoms four hours after the dose and 24 hours after – when compared to the placebo.

At the third measurement, at 25 days, the ketamine-based treatment with antidepressants was no more effective than the placebo with antidepressants.

Current antidepressant treatments take four to six weeks to be fully effective.

The Royal College of Psychiatrists said it was a "significant" study, and suggested it raised the prospect of such a ketamine treatment being available on the NHS. The drug still needs to complete a phase three trial with a much larger group of patients before it could be licensed.

But its major hurdle will be in minimising the risks of harm and abuse, either from esketamine itself or from patients seeking conventional forms of the recreational drug to address cravings.

In a comment on the study the AJP’s editor’s note tighter controls are needed to ensure the drug is available to those who need it but does not lead to an “epidemic of misuse”.

The US is already in the midst of one drug misuse epidemic with opioids, marketed in the 1990s as a non-addictive treatment for chronic pain, fuelling 64,000 deaths in 2016 and costing more than a trillion dollars this century.

Ketamine has been known about since the 1960s and was first used as an anaesthetic before becoming popular recreationally because of its psychotropic effects, which change users’ self-perception.

It has both physical and mental health risks, and can induce a form of psychosis, trials with orally administered ketamine have also proved too slow to enter the system

A paper earlier this year also identified the elusive mechanism that allows it to tackle depression, by preventing an erratic burst firing of signals in the brain that drown out the reward centres.

AJP editor Dr Robert Freedman said doctors have a duty to provide the best possible treatment to their patients, but added: “Protection of the public’s health is part of our responsibility as well, and, as physicians, we are responsible for preventing new drug epidemics.”

Phase three trials should consult widely with public health officials and experts on drug misuse to develop the safest way for the drug to be used.

This would allow the treatment to “continue to be available to those with need, while the population that is at-risk for abuse is protected from an epidemic of misuse,” Freedman added.