Oral Ketamine Experiment Reduces Suicidal Thoughts In Over Two-Thirds Of Patients

Suicide is a major threat to public health. In recent years, suicide rates have actually worsened in the US, and tragically, it's a phenomenon that's accelerating even among children.

There are reasons for hope in the face of this deadly despair, however, and it comes from an unlikely quarter. Ketamine – an anaesthetic discovered in the 1950s – may be dismissed by many as a horse tranquilliser or illicit party drug, but that's far from the whole story about this powerful chemical.

A new study shows oral doses of ketamine can dramatically lower suicidal ideation in patients with chronic suicidal thoughts – the latest finding in a series of experiments forcing us to reevaluate the drug.

In recent years, ketamines's reputation has undergone a makeover of sorts, thanks to new scientific discoveries of the positive effects it can have on people experiencing mental health issues.

A wealth of research has shown that ketamine seems to be capable of treating severe depression, among other conditions.

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While the mysterious mechanisms behind these effects are still being explored, the FDA approved a ketamine-based nasal spray for depression in 2019.

In addition, researchers have found the chemical significantly and quickly reduces suicidal ideation in people who experience such thoughts – which is something traditional antidepressants often fail to achieve, and can take weeks to work if they are in fact successful.

Yet, there's much we still don't know about how effective ketamine is at reducing suicidal thoughts, scientists say.

For starters, most existing experiments assessing the efficacy of the drug on suicidality have delivered it by intravenous (IV) administration – a workable method, but also one that's costly, invasive, and sometimes complication-prone to implement.

Researchers say there's another, simpler, cheaper way.

"An oral form of ketamine that can be administered with ease, and potentially on a more frequent basis, is … an attractive option for the treatment of suicidal ideation," researchers from the University of the Sunshine Coast (USC) in Australia write in a new study.

"However, very few studies have explored the feasibility of low-dose oral ketamine in treating suicidality."

To help bridge that gap, a team led by USC psychiatrist Adem Can conducted an open-label trial where 32 adult patients were given mild, sub-anaesthetic doses of oral ketamine over six weeks, mixed into orange juice, with the dosage increasing over the course of the experiment.

The participants in the study all experienced what is known as chronic suicidality – an ongoing level of suicidal thoughts that linger in the mind over a period of time, but which never rise to acute or extreme risk of suicide.

"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," Can explains.

Despite the chronic nature of their condition, the experiment produced a substantial and rapid-acting response.

"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," says Can.

"In medicine, this response rate is significant, particularly given it was experienced by patients with chronic suicidality, which can be difficult to treat."

Using a test specifically designed to measure levels of suicidal intent, the researchers found that after the six weeks of ketamine treatment, suicidal thoughts had dropped to below the cut-off for clinically significant levels of suicidal ideation for over two-thirds (69 percent) of the group.

A follow-up test taken four weeks later – being four weeks from the final dose – saw a small but significant bump in suicidal thoughts, suggesting the effects of the drug fade with time.


Nonetheless, even at this point, it was still a roughly 50 percent drop in suicidal ideation compared to the pre-treatment levels. Secondary measures of depression and suicidality also saw improvements.

Some of the participants did experience temporary side effects, however, especially early in the study when they were getting used to the effects of the drug. Side effects included decreased energy and fatigue, restlessness, anxiety, and dizziness, among others.

According to the researchers, though, no serious adverse events were recorded, and the drug was generally well tolerated by the group.

What's more, the reduction in suicidal ideation seen is generally in line with what previous experiments delivering ketamine via IV have shown.

While the researchers acknowledge there's much more we still need to learn about ketamine's impact on suicidal behavior, the findings amount to important new evidence of what ketamine can achieve in the short term, and with the practicality of oral dosage too.

"To the best of our knowledge, the current study is the first to explore the feasibility, safety and tolerability of oral ketamine on chronic suicidality in patients who presented with a range of psychiatric conditions including mood, anxiety, and personality disorders," the authors write.

"Overall, oral ketamine led to significant short-term and prolonged improvements in suicidal ideation, affective symptoms, well-being and socio-occupational functioning in this sample of adults with a history of chronic suicidality and [major depressive disorder]."

The findings are reported in Translational Psychiatry.

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