By John Kerr 16/08/2016

New Zealand patients will be part of the world’s largest controlled clinical trial testing the “enormous potential” of ketamine as an antidepressant medication.

A vial of ketamine. Credit: Wikimedia / Psychonaught
A vial of ketamine. Credit: Wikimedia / Psychonaught

Depending on who you ask, the drug ketamine is either a powerful anesthetic, a horse tranquilizer or an illicit narcotic.  However, there is now a growing body of evidence that the drug might also be an effective treatment for depression.

A number of previous studies have shown that low doses of ketamine can quickly reverse some of the symptoms of depression, but there hasn’t been much research into the best way to administer the drug to get lasting results.

“If you give a single treatment, the studies show that you get an amazing anti-depressant response that lasts at least a few days,” says Prof Colleen Loo, a psychiatrist based at the Black Dog Institute in Australia.

“But what no study has shown is how can you use it as a clinically useful treatment to get a lasting response.”

That’s about to change with the world’s largest randomised controlled trial of ketamine as a treatment for depression set to kick off. The three-year trial, led by Prof Loo, will enroll 200 adult patients who have not responded to existing medications for major depression. Researchers will then compare the effects of twice-weekly ketamine treatment against an active placebo treatment over a four-week period.

The trial will include patients recruited from Dunedin, New Zealand, as well as five sites in Australia.

Read more about the trial on

Off-label ketamine ‘irresponsible’

Some doctors are already prescribing ketamine to depressed patients ‘off-label’  i.e. for an unapproved use. In New Zealand, ethical concerns were raised over the prescribing of ketamine to 11 Dunedin patients with treatment-resistant depression in 2010. A report ultimately found that the practice had not breached any ethical guidelines but was “borderline”.

Professor Loo described the practice of off-label prescribing as “premature and irresponsible,” given that the effectiveness and safety of this treatment approach involving repeated dosing has yet to be tested in controlled trials.

“We will be working very closely with clinical pharmacologists during this trial to understand the specific dosage required for each individual and the likely effects it will have,” she said.

How does ketamine treat depression?

The Black Dog Institute website offers an insight into how ketamine is thought to combat depressive symptoms:

Ketamine seems to achieve its effect via the NMDA (N-methyl-D-aspartate) receptors that are lodged in the membrane of the nerve cells that send messages throughout the brain. Some NMDA receptors promote, and some shut down cell growth. In conditions such as bipolar disorder and depression it’s thought that the growth-interrupting receptors may be over-activated and that ketamine may block just enough of the ‘bad’ receptors and allow most of the ‘good’ receptors to keep working.

However, as ketamine temporarily ‘disconnects’ the central nervous system from the perception of external stimuli, it can have disorienting ‘psychotomimetic’ side effects (psychosis-like perceptions and behavioural changes), such as out-of-body experiences, a sense of intoxication or seeing psychedelic lights (accounting for its use as a recreational ‘street’ drug). It can also have temporary ‘dissociative’ effects (a psychological experience of alienation or unreality): in fact, research suggests that dissociative side effects may be a clinical biomarker that predicts ketamine’s efficacy in lifting mood.


Featured image: Sadness. Kyla Duhamel / Flickr

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