Researchers in Christchurch are calling for more people living with treatment-resistant depression to take part in a clinical trial combining oral ketamine with a proven form of psychotherapy.
The trial, led by the University of Otago, Christchurch, aims to tackle the high rates of relapse many patients experience once they stop ketamine treatment. The study is testing whether combining oral doses of ketamine with Behavioural Activation Therapy (BAT) can help people stay well for longer.
Since launching last year, researchers have been recruiting 60 participants from Christchurch and Dunedin who have not responded to regular anti-depressant medication. So far, 28 people have taken part, but more volunteers are needed to reach a definitive conclusion.
Associate Professor Ben Beaglehole, lead investigator from the university’s Department of Psychological Medicine, said ketamine is one of the most exciting new treatments for depression in a generation.
“We are already seeing benefits from the eight-week course of oral ketamine we have offered our trial participants so far, although it’s still too early to tell whether the addition of BAT is offering protection against the biggest problem many patients taking ketamine experience – the high rates of relapse within days or weeks of treatment ending,” Beaglehole said.
“We need more patients to join the trial to help give us answers.”
BAT works by targeting the inactivity that is common in depression, aiming to get people moving emotionally and physically to help lift their mood.
“We chose BAT because it’s an easily accessible and affordable solution for people to embed into their daily lives,” Beaglehole said.
The three-year Health Research Council of New Zealand-funded study is looking for more volunteers aged 18 to 65 who have tried at least two types of antidepressant medications without success. All participants will receive ketamine twice weekly for eight weeks, while half will also complete BAT. Both groups will be monitored for 12 weeks after treatment to measure whether BAT helps maintain improvements.
Beaglehole said most studies involving ketamine focus on injected doses, which can cause strong dissociative effects or a “trip.”
“In our study, participants swallow ketamine. It works more slowly, is easier to tolerate, and lessens the ‘trip’ effect,” he said.
However, Beaglehole said potential participants should know the trial has limits.
“The study may be a bit of a roller coaster due to the fact that if they respond, we are not in a position to continue their ketamine treatment once the trial ends,” he said.
The research team has also developed guidelines to help Specialist Mental Health Services safely prescribe ketamine and manage patients receiving the treatment.
Beaglehole said using ketamine for depression remains challenging because while it works well in the short term, depression is a long-term condition.
“Ketamine should be reserved for treatment-resistant depression, but even then, it’s tricky to know how long to continue treatment and how to manage relapses,” he said.
Ketamine has been legally used by doctors in New Zealand since the 1950s for sedation and pain relief but has been classified as an illegal drug for recreational use since the 1980s.
Beaglehole said the trial uses ketamine in a tightly controlled setting to reduce risks around its abuse potential, as well as known side effects including bladder issues and possible memory problems.
The trial is part of a broader body of University of Otago research examining ketamine’s potential in treating depression, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD). While studies on depression and OCD have shown short-term benefits, the PTSD study is still under review.
“Depression is the most common mental illness worldwide and one of the most burdensome health problems globally,” Beaglehole said.
“If our trial shows BAT can help delay relapse, it will give genuine hope to people with treatment-resistant depression and support clinicians in safely using the drug in the community.”
