A $2.1 million grant from the National Health and Medical Research Council announced today will see UNSW lead Australia’s largest clinical trial to further explore the potential of ketamine as a new treatment for major depression.

The trial will enrol 200 patients, who have not responded to existing medications, to compare the effects of ketamine against an active placebo treatment over a four-week period. Trial recruitment is expected to start around April 2016.

Ketamine research leader Professor Colleen Loo, from UNSW’s School of Psychiatry and the Black Dog Institute, welcomed the grant and said it would allow UNSW and Australia to continue its pioneering research in this area.

“This trial builds on five years of research and will be the largest worldwide trial of this scale that is university-based and government-funded.”

Prior studies have shown a single dose of ketamine can reduce depressive symptoms within hours, even in treatment-resistant patients.

“The trial will allow us to examine whether the positive effects of ketamine on an individual’s depression are sustained over a longer period, using the gold standard approach for research, a randomised control trial,” Professor Loo said.

In earlier studies conducted at the Wesley Hospital, Sydney, Professor Loo and the UNSW team tested new approaches for using ketamine to treat depression, including better methods for administering ketamine and the effects of different doses.

These studies found that the intravenous delivery of ketamine over 40 minutes, which has been used in most other trials, is not likely to be the best treatment method.

“Our results also found that dose levels are very important in determining effectiveness and side effects, and that a more tailored approach to dosing for individual patients is important,” Professor Loo said.

The safety and effects of ketamine will be carefully studied in the upcoming trial.

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

The UNSW research team will also study the potential for ketamine to rapidly remove suicidal thoughts, due to rapid improvements in mood within hours of treatment.

The UNSW research team will collaborate with The Black Dog Institute, The George Institute and mood disorders experts from around Australia including Sydney, Monash, Deakin, Western Australia and Adelaide universities, along with the University of Otago in New Zealand.

How does ketamine work?

Ketamine targets a key signalling chemical in the brain known as glutamate. This contrasts with other antidepressant medications, which alter different brain neurotransmitters such as serotonin and noradrenaline.

Researchers believe this may be why the effects of ketamine appear distinct to those of other antidepressant drugs and is faster acting and results in more powerful effects. Studies have shown that ketamine can strongly promote the growth and functioning of brain cells. Prior research has also shown that brain cells can shrink when people are depressed, so the earlier finding that ketamine can reverse these changes is important.

However, as ketamine temporarily ‘disconnects’ the central nervous system from the perception of external stimuli, it can have disorienting or dissociative side effects, such as out-of-body experiences, a sense of intoxication or seeing psychedelic lights, accounting for its use as a recreational drug. These effects are short lived, typically lasting half an hour after each treatment, whereas beneficial mood effects persist for days.