Most studies on ketamine and depression tend to inject participants with ketamine “but when you get a hit of ketamine over a short period of time . . . people have a ‘trip’, they have a mind altering experience”.

Beaglehole, who is based at the Christchurch campus, says it's not clear if that mind-altering experience is necessary for the improvement, or is just a side effect that needs to be managed.

As part of the Otago study, participants will sip the ketamine over an hour to minimise any mind-altering experience and give those patients a “genuine improvement in their mood that typically lasts days”.

That's the challenge with ketamine, “although it looks promising and exciting as a short term treatment, it wears off”.

Ketamine has been used legally by doctors in New Zealand since the 1950s for sedation and pain relief, but it has been  classified as an illegal drug for recreational use since the 1980s.

Beaglehole says this specific trial is after those who still have significant depressive symptoms, despite having tried at least two medications.

The community trial means study participants will remain at their own homes and while unpaid, those involved will receive transport assistance “because we don't want people driving after they have had the ketamine treatment”.

The use of ketamine would be tightly controlled to minimise the potential abuse, including a monitoring period for three months.

The addition of Behavioural Activation Therapy, by engaging in healthy activities which bring enjoyment to participants, is the most important aspect of the trial, says Beaglehole.

Both groups will be monitored for a further 12 weeks after treatment finishes to see if BAT helps maintain improvements to mood once ketamine treatment ends.

“The study may be a bit of a roller-coaster, due to the fact that if participants do respond, we are not in a position to continue their ketamine after the trial ends,” he warns.

That means participants will have to be prepared that their mood may deteriorate once the ketamine treatment stops, but it's hoped the BAT treatment will mean the people with treatment-resistant depression will feel emotionally stronger than before.

“If this trial is effective and can be proven to help delay relapse, it will give genuine hope to people with treatment-resistant depression, and support clinicians more widely in their community use of the drug.”