Should ketamine be used to treat depression?

Building on several smaller trials in the US and Europe, Antipodean researchers are launching the largest randomised control trial into the use of ketamine for patients suffering from long-term depression. Current evidence indicates that ketamine is highly effective in treating severe depression, especially in patients displaying suicidal tendencies but, to date, there has not been a randomised double blind trial to definitively determine the efficacy of ketamine treatment or the implications for long-term use.

Researchers across Australia and New Zealand will enrol 200 adult patients over a three-year trial to receive twice-weekly ketamine treatments over a four-week period. They are seeking patients who have not responded to other depression medications and have experienced extended periods of low mood which significantly impacts their ability to function on a daily basis.

The research is led by Professor Colleen Loo of the University of New South Wales, in conjunction with the Black Dog Institute. Over the last five years, UNSW has conducted extensive research into ketamine as a treatment for depression.

“Ten separate randomised, placebo-controlled trials involving about 250 participants worldwide have shown a single dose of ketamine produces rapid antidepressant effects within hours, even in treatment-resistant patients,” Professor Loo stated. The problem has been in attaining lasting remission and determining safe dosage levels for ongoing treatment. Given ketamine’s history as a recreational drug, safety considerations are paramount.

Neither patients nor researchers will know which participants are receiving placebos in this randomised double blind trial. Professor Loo explained, “This trial will allow us to examine the effects of repeated dosing and whether the positive effects of ketamine on an individual’s depression can be sustained over a longer period.”

The four-week trial will be followed by four weeks of monitoring patients’ mood levels and participants will then be at the top of the list for receiving ongoing ketamine treatment. Professor Loo said, “We will be working very closely with clinical pharmacologists during this trial to understand the specific dosage required for each individual and the likely effects it will have.”

Unregulated use of ketamine as a depression treatment has become popular in recent years, but Professor Loo believes that an evidence-based approach to assessing the effectiveness and safety of this treatment is essential.

“Some clinics in Australia and overseas continue to offer off-label ketamine treatments to patients with depression in an unsafe manner and with minimal care,” she said. “This practice is premature and irresponsible, given that the effectiveness and safety of this treatment approach involving repeated dosing has yet to be tested in controlled trials.”

The trial has been funded by the National Health and Medical Research Council and will be conducted at the following institutions: UNSW/Black Dog Institute, Sydney; Brain and Mind Centre/Royal Prince Alfred Hospital, Sydney;  Monash Alfred Psychiatry Research Centre, Melbourne; South Eastern Private Hospital, Victoria; Adelaide University/Royal Adelaide Hospital, Adelaide; Sir Charles Gairdner Hospital, Perth; and in New Zealand at the University of Otago, Dunedin.

Image caption: Ketamine research leader UNSW Professor Colleen Loo. ©Grant Turner/Mediakoo