Ketamine has a wild reputation. It’s used as party drug thanks to its hallucinogenic effect, but it’s also widely used in medicine as a general anaesthetic and for pain relief. The interactions of the drug on the brain have led to increasing interest from psychiatrists for treating mental health conditions.
Now, a new study from University of the Sunshine Coast (USC), Queensland, has found that oral doses of ketamine administered in a clinical setting can provide a rapid-acting treatment for chronic suicidality.
Currently antidepressants are typically used to treat mood disorders – of which suicide ideation may be a symptom. Antidepressants have some downsides, including that they may take several weeks to have a positive effect, if they make a difference at all.
Antidepressants primarily target monoaminergic neurotransmitters: dopamine, noradrenaline and serotonin. They don’t direct affect the primary excitatory and inhibitory neurotransmitters glutamate and gamma aminobutyric acid. However, all of these are involved in the pathophysiology of depression.
The study from USC’s Thompson Institute, published in Translational Psychiatry, showed that within the first six weeks, 69% of participants achieved a clinical reduction in suicide ideation.
It involved 32 adults with chronic suicidal thoughts in an open-label trial of sub-anaesthetic doses of oral ketamine. Under the supervision of a consultant psychiatrist, they began on 0.5 mg/kg of the drug administered as a liquid in fruit juice, which was titrated to a maximum 3.0 mg/kg. This was a comparatively conservative dose to ensure that participants could tolerate the treatment with temporary side effects.
“On average, patients experienced a significant reduction in suicide ideation, from a high level before the trial to below the clinical threshold by week six of the trial,” said psychiatrist Adem Can, the study’s principal investigator.
“These patients had lived with suicidality for a very long time and presented a range of psychiatric conditions, including mood, anxiety and personality disorders, and many of them had lost hope of recovery.”
The treatment also had prolonged benefits, with 50% of the participants still showing a significant improvement at the post-ketamine follow-up at week 10. The results were consistent with past studies using intravenous ketamine, suggesting that oral ketamine is a viable treatment option for chronic suicidality.
“Intravenous administration, however, is invasive, expensive and carries a higher chance of adverse reactions due to its injection straight into the blood stream,” Can says. “So logistically it is a lot easier and faster to clinically administer an oral dose.”
USC Thompson Institute director and study supervisor Jim Lagopoulos has been researching the potential therapeutic benefits of ketamine for 20 years, and said the findings were a significant development.
“We also had a very complex group of patients with a variety of conditions such as depression, anxiety, borderline personality disorder – all factors that can increase your potential for suicidality – yet the treatment still worked across the group,” says Lagopolous.
“This means the trial group was representative of the community we are serving, where suicidality is often accompanied by one or more other conditions. So results like these across the spectrum are very encouraging.”
Although this study had some limitations – there was no placebo or control group – it provided encouraging evidence to the feasibility of ketamine treatments.
It demonstrated the range in which dosage could be adjusted according to a patient’s physiology and tolerance to the treatment, while still reducing suicidality.