Around 700,000 people worldwide die by suicide annually, and up to 20 times this number attempt suicide. Most suicide ideas will not lead to a suicidal act; all suicidal acts are preceded by suicidal thoughts. Thus, rapidly resolving a suicidal crisis before it is acted on might prevent many deaths.

Ketamine is a fast-acting, efficient treatment for patients hospitalised for severe suicidal thoughts (ideation), finds a clinical trial published by The BMJ today.

The results suggested that some patients with severe suicidal thoughts, particularly those with bipolar disorder, could benefit from ketamine, as current treatment options are limited.

Treating suicidal thoughts with ketamine

Ketamine is a powerful and quick-acting sedative, which rapidly deadens pain without loss of consciousness. It is approved as an aesthetic but is also a promising drug to rapidly reduce suicidal thoughts. However, poor-quality studies have left too much uncertainty about the balance of benefits and harms in this situation to provide clinically useful evidence.

To address this, researchers investigated the anti-suicidal effects of ketamine over a six-week period amongst 156 patients (aged 18 or over) voluntarily admitted to a hospital in France with severe suicidal thoughts between April 2015 and March 2019.

Before starting the trial, patients completed a thorough clinical assessment and were divided into three diagnostic groups: bipolar disorder, depressive disorder, or other psychiatric disorders.

Patients were randomly allocated to receive two 40-minute intravenous infusions of either ketamine or placebo (saline) over 24 hours, in addition to the usual treatment. The researchers then assessed the rate of patients in full suicidal remission at day three, confirmed by a score of three or less on a clinical rates scale for suicidal thoughts based on 19 items score zero to two (maximum score 38).

The results of the study

The researchers found that more patients receiving ketamine reached full remission of suicidal thoughts at day three than those receiving placebo (63% of patients in the ketamine group compared with 32% in the placebo group). All side effects were rated as minor and reduced significantly between the first assessment and day four.

In the ketamine group, one patient died from suicide, although this was determined by the oversight committee to be unrelated to the intervention. These results were unchanged after adjusting for other potentially influential factors.

Ketamine’s effect was greatest in patients with bipolar disorder, whereas no meaningful benefits were seen in patients with major depression or other mental illnesses. However, caution must be exercised because the data is from a small number of participants.

The drug also appeared to relieve psychological pain, and the researchers suggested that this analgesic effect might explain its benefits on the reduction of suicidal thoughts. However, the study uncovered that ketamine was not effective at weeks four and six.

These findings indicated that ketamine is rapid, safe, and effective in the short term for acute care in hospitalised suicidal patients, they wrote. However, they stress that ketamine is a drug with a potential for abuse and say longer follow-up of larger samples will be necessary to examine benefits on suicidal behaviours and long-term harm.

This new trial challenges current thinking about ketamine said psychiatry specialist Riccardo De Giorgi in a linked editorial.

Whilst it provides evidence that ketamine reduces suicidal thoughts in some people, he questioned whether ketamine will be given to eligible patients with suicidal thoughts any time soon, “given the plausible concern that the widespread use of ketamine might trigger a new opioid style crisis.”

Whether the emergency use of ketamine for suicidal crises will be recommended in practice depends on many other factors, he added, including the values and preferences of patients, clinicians, researchers, and policymakers.

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