Ketamine for suicide prevention

Suicidal ideation, its impact and its treatment

Today, suicide is the fourth leading cause of death among young people between the ages of 15 and 29 ⁽¹⁾. Nearly 800,000 people die from it each year, and many more make one or more suicide attempts. In Spain, suicide is the leading cause of death between young people ⁽²⁾ due to external causes. The stigma that surrounds it means that many will hide their thoughts and plans about suicide, or what we know as suicidal ideation (SI). Although suicidal ideation does not always lead to the action itself, it is indisputable that it carries a great risk that only increases over time. For this reason, early detection and rapid treatment are vital for its prevention, as well as destigmatizing its discussion in daily life.

Suicidal ideation does not always come in conjunction with a diagnosis of depression or another illness, but it does often co-occur with them. One possible treatment is the use of antidepressants, but one of the biggest problems we find here is their delayed onset of action; they take several weeks to start working. It is also common to have to try several types before finding the right one, spending precious time during which the risk of suicide can be high. Statistically, there is also evidence towards an increased risk of suicide for those under the age of 25 who are prescribed SSRI antidepressants ⁽³⁾. Additionally, antidepressants are not recommended for all types of patients, for example, those with bipolar disorder. Psychotherapy is also often helpful, but again we run into the same problem: it is not immediate, and often with suicidal ideation we might not have that much time available.

Therefore, it is vital to find a method that acts quickly, and ketamine is a potential candidate that has shown important changes from the first hours of administration. Although esketamine or S-ketamine, a drug modified from ketamine to be administered intranasally, has also shown good results in patients with depression, evidence points to a markedly greater impact of racemic ketamine, typically administered intravenously, on the reduction of suicidal ideation ⁽⁴⁾.

The evidence

A study by Abbar and colleagues.⁵, published in 2022, investigates the effect of ketamine on suicidal ideation during the first six weeks after administration. Across seven hospitals in France, researchers recruited a total of 156 participants diagnosed with bipolar disorder, depression, or other psychiatric disorders (such as post-traumatic stress or generalized anxiety disorder). They were randomly divided into two groups: one received an intravenous infusion of ketamine, administered twice within 24 hours, while the second group received the placebo, a saline solution also administered intravenously. It was a double-blind study. Various follow-ups were performed over the following weeks, during which the patients’ usual care (such as hospital visits, psychotherapy, and assessments with family) also continued.

It was found that 63% of patients experienced complete remission of symptoms within 3 days, versus 31% with placebo. From these, 43% had complete remission after just 2 hours, and there was no increase in suicidal ideation after ketamine administration. Distinguishing between the three groups explored, the greatest improvement was detected in the group with bipolar personality disorder, also highlighting the absence of mood swings during the days of treatment. The improvement was considerably less significant for the group diagnosed with other disorders, but the heterogeneity of the group may have caused disparate results. A more exhaustive and specific exploration of the other disorders would be necessary to determine if ketamine is effective in their treatment.

Surprisingly, considering the extensive evidence in the treatment of depression, the group diagnosed with this disorder did not experience a significant improvement in suicidal ideation. The authors here point out that this group was the most sensitive to placebo (those who experienced the most improvement with it) and therefore the analysis may not have been sensitive enough to detect a specific difference between placebo and ketamine. There is also evidence that patients with depression, especially when it is treatment-resistant depression, require a greater number of sessions to experience complete remission.

Although the exact mechanism through which ketamine works is not known, levels of psychological pain have been associated with suicidal ideation (psychological pain can be caused by things like the loss of someone close to you, but for thise diagnosed with mood disorders, psychological pain is often present without any specific cause), and therefore it has been postulated that the analgesic effect of ketamine reduces this mental pain. Some have suggested that ketamine in depression may involve the opioid system, although this opinion is highly debated. In future posts we will explore the current theories and evidence about the mechanisms of action of ketamine in our body and mind. As with depression, it is vital to continue studying the effect of ketamine on suicidal ideation in the long term, with follow-ups over the years evaluating relapses and exploring the use of maintenance doses. However, it is indisputable that ketamine can be of great use for the treatment of suicidal ideation and suicide prevention, especially for high-risk populations such as those diagnosed with bipolar disorder.

References

• World Health Organization: WHO. Suicidio [Internet]. Who.int. World Health Organization: WHO; 2021. Available from: https://www.who.int/es/news-room/fact-sheets/detail/suicide

• Suicidios en adolescentes en España: factores de riesgo y datos [Internet]. Save the Children. 2022. Available from: https://www.savethechildren.es/actualidad/suicidios-adolescentes-espana-factores-riesgo-datos

• Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 3. Pharmacological Treatments. Can J Psychiatry [Internet]. 2016;61(9):540–60. Available from: http://dx.doi.org/10.1177/0706743716659417

• Siegel AN, Di Vincenzo JD, Brietzke E, Gill H, Rodrigues NB, Lui LMW, et al. Antisuicidal and antidepressant effects of ketamine and esketamine in patients with baseline suicidality: A systematic review. J Psychiatr Res [Internet]. 2021;137:426–36. Available from: http://dx.doi.org/10.1016/j.jpsychires.2021.03.009

• Abbar M, Demattei C, El-Hage W, Llorca P-M, Samalin L, Demaricourt P, et al. Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. BMJ [Internet]. 2022;e067194. Available from: http://dx.doi.org/10.1136/bmj-2021-067194