Trials are underway for a potentially groundbreaking new antidepressant, with significant breakthroughs reported in severely depressed participants.
The medication is characterised by the slow release of ketamine, a drug clinically used in anaesthesia for decades. Ketamine has also been recognised for producing an antidepressant effect, with low intravenous doses tested in the mid-2000s. However, a side effect typically reported was dissociation - a disconnection and lack of continuity between thoughts, memories, surroundings, actions and identity.
Since then, pharmaceutical scientists have aimed to create a convenient, oral antidepressant that releases ketamine at an incredibly slow rate. New Zealand has taken part in the ongoing trials, with work on the drug beginning in 2017. Two more trial sites are now set to be opened in Tauranga and Rotorua, with three existing locations in Auckland, Christchurch and Dunedin.
Douglas Pharmaceuticals chief scientific officer, Dr Peter Surman, appeared on The AM Show on Wednesday to discuss the major breakthroughs reported in the trials. Seventy-five percent of participants have reported a drastically-reduced score on the Montgomery-Asberg Depression Rating Scale (MADRS), Dr Surman said, a diagnostic questionnaire used by psychiatrists to measure the severity of depressive episodes in patients with mood disorders.
He says in the initial trial of seven severely depressed patients, a "pronounced effect" was recorded. Within two days of taking the drug, the patients were "well", he said, and remained well for three months on a continual low dose.
The results of the initial study encouraged the developers to present their case before the US Food and Drug Administration (FDA).
"They blessed the study for us for phase two and 150 patients," Dr Surman said. "We've got maybe 120 enriched patients [patients with depression]. They come in, they get dosed for a week on an open-label [a clinical trial in which information is not withheld from trial participants], so the doctor and patient know what they're taking. They take the drug once a day, and at the end of the week the psychiatrist objectively measures their depression score."
Upon commencing the study, patients were reporting scores in the 30s. MADRS scores of 20 or more indicate clinical depression. Scores of 30 or more indicate that the patient's quality of life and daily functioning is significantly impacted by their illness.
Dr Surman said that by day eight, patients were reporting an average MADRS score of 10.
"Below 12 is like all of us. We could all have a score like that," he said.
Dr Surman noted that the pronounced results are unusual, with the majority of antidepressant drugs - like selective serotonin reuptake inhibitors (SSRIs) - taking around six to eight weeks to have an effect on patients.
"We think here if it carries on, and safety and efficacy keeps being shown through these studies, this would be the first rapidly-acting antidepressant as an oral dose," he told The AM Show.
"It would provide a lot of help in emergency settings potentially down the track. At the moment we're looking at treatment-resistant patients - those who have found one, two or more antidepressants [don't work for them]. The only thing they really have is maybe counselling or electroconvulsive therapy. There are a lot of people out there who are treatment-resistant, maybe a third of depression patients. If you could reach even 30 percent of them, it would be 50,000 people in New Zealand."
No demographic trends - such as efficacy being dependent on gender, age or race - have clearly emerged so far. Trials are beginning in Taiwan and Singapore, Dr Surman said, the results of which will show how well the drug works in Asian populations, or whether the dose needs to be adjusted depending on ethnic background.
The trials are currently working to establish the optimal dose of the ketamine antidepressant, which will be taken into the pivotal phase three trials.
Side effects appear minimal, with dissociation, spaciness and headaches reported early on but not as the trials progressed, he noted.
Phase two trials are ongoing, with 100 randomised patients. Douglas Pharmaceuticals is now looking for 50 additional participants, with another two sites opening in New Zealand due to heightened interest from local psychiatrists. There are now five sites nationwide in Auckland, Christchurch, Dunedin, Tauranga and Rotorua - the latter two being the most recent to open.
"We've had great interest from psychiatrists in the middle North Island to become part of this… if we get a good read from the Government, from Medsafe, from TGA, with the FDA, hopefully there can be some fast-tracking to the process to go through phase three."
With phase two tentatively set to wrap-up in 2021 and phase three set to conclude in 2023 and a year of review, 2024 is the very earliest the medicine may become available.
"It's being driven now by psychiatrists. They're the ones pushing us," Dr Surman said.
"It's fantastic to be on a project like this."
