Researchers are seeking more people living with treatment-resistant depression to join a novel trial combining oral ketamine with a proven form of psychotherapy, in the hope they can stay well for longer.
The trial, led by the University of Otago, Christchurch, is seeking a solution for the high rates of relapse experienced by many patients who come off ketamine treatment, by combining oral doses of ketamine with Behavioural Activation Therapy (BAT).
Launched last year, the trial has been seeking 60 patient recruits from Christchurch and Dunedin for whom regular anti-depressant therapy has repeatedly failed.
Study lead investigator Associate Professor Ben Beaglehole, from Christchurch campus’s Department of Psychological Medicine, says while 28 participants have taken part, more are being sought to help the trial reach definitive conclusions.
Associate Professor Ben Beaglehole
“Ketamine is probably the most exciting new treatment for depression for a generation,” Associate Professor Beaglehole says.
“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. We need more patients to join the trial to help give us answers.”
BAT aims to activate people with depression, targeting the inactivity which is often part and parcel of the disease, as a means of getting them moving – both emotionally and physically – to encourage a lift in mood.
“We chose BAT because it’s an easily accessible and affordable solution for people to embed into their daily lives,” Associate Professor Beaglehole says.
The three-year Health Research Council of New Zealand study is seeking more volunteers aged 18-65 for whom two different types of anti-depressant medication has not worked. All will receive ketamine twice weekly for eight weeks, with half also receiving BAT for eight weeks. Both groups will be monitored for a further 12 weeks after treatment finishes to see if BAT helps maintain improvements in mood.
Associate Professor Beaglehole says most studies on ketamine as a treatment for depression have focussed on injected ketamine, which can lead to a strong dissociative reaction or ‘trip’.
“However, in our study, participants are being given ketamine to swallow, which works more slowly, is easier to tolerate and lessens the ‘trip’ effect,” he explains.
He says there is one potential issue participants need to be prepared for.
“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.”
The research team has also published a guideline aimed at giving Specialist Mental Health Services direction about how to prescribe ketamine to mental health patients, and how to manage them once on it.
Associate Professor Beaglehole says decisions about using ketamine are challenging because although the evidence suggests it works very well in the short-term, depression is a longer-term health problem.
“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,” Associate Professor Beaglehole says.
The anaesthetic drug has been used legally by doctors in New Zealand since the 1950s for sedation and pain relief but classified as an illegal drug for recreational use since the 1980s.
Associate Professor Beaglehole says the ketamine in this trial is being given in a tightly controlled setting to minimise concerns about its abuse potential, alongside concerns it can lead to bladder issues and possible memory side effects.
This is the latest in a body of clinical research on ketamine carried out by the University of Otago, examining its use for depression, as well as obsessive compulsive disorder (OCD) and post traumatic stress disorder (PTSD). The depression and OCD studies both reported short-term benefits for ketamine use; the PTSD study is still under review but has also found short-term benefits.
“Depression is the most common mental illness worldwide and one of the most burdensome health problems globally,” Associate Professor Beaglehole says.
“If our completed trial is effective and BAT 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.”