A recent study published in Translational Psychiatry found that ketamine, a medication typically used as an anesthetic, may significantly reduce suicidal thoughts in individuals with recurrent major depressive disorder (MDD) compared to those prescribed more common antidepressants. The research shows that those prescribed ketamine had a lower risk of developing suicidal ideation over the short and long term, up to 270 days following treatment, compared to patients taking other antidepressants.
Major depressive disorder is a widespread condition that often recurs, meaning individuals who experience one episode of depression are highly likely to have future episodes. Recurrent MDD can be particularly challenging to treat, and many patients do not respond to traditional antidepressants. Suicidal ideation, or thoughts of suicide, is common among those with MDD and poses a major public health concern, as suicide remains one of the leading causes of death in the United States.
In recent years, ketamine has emerged as a promising treatment option for people with treatment-resistant depression. Research suggests that it can provide rapid relief from depressive symptoms, including suicidal ideation. However, most studies on ketamine’s effects have focused on the short term, and there is limited evidence regarding its long-term impact on suicidal thoughts.
“Ketamine is increasingly used for managing depression. Recent clinical trials showed promising benefits (relatively short follow-up time). However, long-term real-world evidence of effects of ketamine in patients of MDD is lacking,” said study author Rong Xu, a professor of biomedical informatics and director of the Center for Artificial Intelligence in Drug Discovery at Case Western Reserve University School of Medicine.
The research team conducted a retrospective cohort study using data from the TriNetX US Collaborative Network, a platform that aggregates electronic health records from millions of patients across 62 healthcare organizations. This network provided access to data from over 108 million patients, allowing the researchers to study a large and diverse group of individuals with recurrent MDD.
The study focused on 514,988 patients who had been diagnosed with recurrent MDD and were prescribed antidepressants between January 2019 and January 2023. The researchers divided the patients into two groups: those who were prescribed ketamine and those who were prescribed more common antidepressants such as fluoxetine, sertraline, or bupropion. Patients prescribed ketamine could also have been taking other antidepressants, as ketamine is often used alongside other treatments.
To ensure the two groups were comparable, the researchers used a method called propensity-score matching, which balances the groups based on various factors such as age, gender, race, medical history, and socioeconomic status. This technique helps minimize potential biases that could affect the results. After matching, each group had 21,372 patients, allowing for a fair comparison of the effects of ketamine versus other antidepressants.
The primary outcome the researchers examined was the presence of suicidal ideation, as recorded in patients’ health records. They tracked the occurrence of suicidal thoughts in both groups over different time periods, ranging from one week to 270 days after the initial prescription.
The study found that ketamine was associated with a significantly lower risk of suicidal ideation compared to other antidepressants. Within the first week of treatment, patients prescribed ketamine were about 37% less likely to develop suicidal thoughts. This effect remained consistent over time, with the risk being about 22% lower even after 270 days.
“Our study showed potential benefits of ketamine in reducing sucide risk in patients with MDD compared with other antidepressants,” Xu told PsyPost.
The beneficial effects of ketamine were particularly notable in certain demographic groups. Patients over the age of 24, both male and female, saw the most significant reductions in suicidal ideation. White patients also experienced a greater reduction in suicidal thoughts compared to those prescribed other antidepressants.
However, no significant difference was observed for patients under the age of 24 or for Black patients. The researchers suggest that these variations might be due to smaller sample sizes in these subgroups, which could limit the strength of the findings. Future studies with larger and more diverse samples are needed to better understand how ketamine affects different populations.
Despite its promising findings, the study has several limitations. First, because it is a retrospective study based on electronic health records, it is difficult to establish a cause-and-effect relationship between ketamine use and reduced suicidal ideation. The study can only show an association, meaning it is possible that other factors not accounted for in the data influenced the results.
“This is an associational study using patient electronic health records, which has inherent limitations of unmeasured and uncontrolled confounding and biases,” Xu noted. “Therefore, no causal inference can be drawn.”
Future research could focus on comparing ketamine directly with specific antidepressants and other non-drug treatments, such as therapy or electroconvulsive therapy. Additionally, understanding the optimal dosage and duration of ketamine treatment for reducing suicidal thoughts is an important next step.
“We will continue to monitor the risk and benefits of ketamine in real-world patients with MDD,” Xu said.
The study, “Suicidal ideation following ketamine prescription in patients with recurrent major depressive disorder: a nation-wide cohort study,” was authored by Yiheng Pan, Maria P. Gorenflo, Pamela B. Davis, David C. Kaelber, Susan De Luca, and Rong Xu.
