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The participants kinda started tripping. (GoaShape/Unsplash)

Snorting Ketamine May Not Be The Best Way to Treat Depression, Study Shows

Bad, bad side-effects. 

SIGNE DEAN
19 MAR 2018

The anaesthetic drug ketamine has recently emerged as a promising new depression treatment - especially for those with a particularly stubborn illness that doesn't respond to conventional antidepressants.

 

But now the unsuccessful results of a pilot study for a ketamine nasal spray show there's still more work to do until we find the best way to use this drug as a depression treatment.

Led by researchers from the Black Dog institute in Australia, the small pilot trial was supposed to be a first step to investigate how repeatedly snorting ketamine as a nasal spray might work for patients with severe and treatment-resistant depression.

Unfortunately, they discovered that the side-effects from an intranasal ketamine spray are worse than anyone could have expected.

Previous clinical trials have shown that a single dose of intravenous (IV) ketamine can be remarkably effective as a fast-acting antidepressant. But that single dose - which is lower than what's used for anaesthetic purposes - tends to wear off after a couple weeks at most.

If we're going to add ketamine to the antidepressant drug arsenal, we need to know whether repeated doses over longer periods of time are safe and feasible - which is what the pilot trial set out to examine.

 

The researchers turned their attention to the nasal spray route because snorting a medication can have several benefits - it gets into the bloodstream faster, it doesn't have to go through the stomach as a tablet would, and there's a pleasant lack of needles in comparison to IV ketamine.

The team planned to recruit a total of ten participants with treatment-resistant depression, but ended up cutting the study short after the first five experienced some seriously nasty side-effects.

In a double-blind, randomised and controlled set-up, each patient spent four weeks receiving a total of eight treatments of ten doses - either a ketamine nasal spray, or midazolam, a calming and sedative drug used as an 'active control' in this case.

All participants were trained to self-administer the nasal sprays, a process not dissimilar from any other nasal spray medication you might use when you have a cold. But they couldn't even get through the ten sprays needed to get the full dose.

As soon as the ketamine hit their bloodstreams, the subjects started losing motor coordination, which got so bad that none of them managed to do all the sprays without the help of research staff monitoring the treatment.

 

When the researchers tried to space out the nasal sprays with a five minute interval, things only got worse - the subjects' blood pressure shot up, and they started experiencing psychotic-like effects as well.

Ketamine is well-known as a psychedelic party drug, so it's not entirely surprising that snorting it caused some pretty wild experiences for the participants.

"Intranasal ketamine delivery is very potent as it bypasses metabolic pathways, and ketamine is rapidly absorbed into the bloodstream," explained senior researcher Colleen Loo from the University of New South Wales in Sydney, Australia.

"But as our findings show, this can lead to problems with high peak levels of ketamine in some people causing problematic side effects."

The team's findings are actually different from an earlier ketamine nasal spray trial done in 2014, in which the drug was well tolerated. The researchers of this newest pilot study attribute the better tolerance to a lower dosage (50mg as opposed to 100mg) as well as the training of their participants to deliver the nasal spray as effectively as possible - thus they ended up with higher levels of the drug in their bloodstreams.

"Our results suggest that absorption via the intranasal mucosa may be too rapid when careful attention is paid to the administration technique, resulting in the development of rapid and intense side effects," the team writes in the study.

Because the study had to be cut short, the team doesn't have conclusive results on whether the ketamine even helped the depression; given the massive problems with the nasal spray route, that's kind-of a moot point anyway.

But this doesn't mean that ketamine is useless as an antidepressant - even if snorting a standardised dose turned out disastrous for those who want to treat their depressive symptoms and remain lucid.

There are still more options to explore for the scientists. Loo's team is now recruiting participants for the world's largest ketamine depression treatment trial involving injections. And nasal sprays are not completely ruled out, either.

"Our prior research has shown that altering the dose on an individual patient basis was important," Loo said.

"[But] more research is needed to identify the optimal level of ketamine dosage for each specific application method before nasal sprays can be considered a feasible treatment option."

The study has been published in the Journal of Psychopharmacology.

 
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