Ketamine offers short-term benefits to patients with suicidal ideation, French study finds
Ketamine provided rapid benefits to hospitalized patients with suicidal ideation; however, more research is needed to determine its long-term impact, according to findings from a French study published in The BMJ.
“No available treatment, such as antidepressants, have so rapid positive effects on suicidal ideation,” Fabrice Jollant, MD, PhD, an adjunct professor in the department of psychiatry at McGill University in Montreal and a professor of psychiatry at Université de Paris and Sainte-Anne Hospital in Paris, told Healio. “This is an important and quite unique benefit of ketamine to date.”
In a 6-week prospective, double-blind, superiority, randomized, placebo-controlled trial, Jollant and colleagues assessed the rapid anti-suicidal benefits of ketamine for adults with current suicidal ideation who were voluntarily admitted to one of seven French teaching hospitals between April 13, 2015, and March 12, 2019. The Academic Hospital of Nîmes served as the leading research center.
In total, the researchers enrolled 156 patients; 73 were randomly assigned to receive ketamine in two 40-minute intravenous infusions of 0.5 mg/kg at baseline and at the 24-hour mark. The remaining participants received infusions of saline. All patients were provided with usual treatment for suicidal ideation.
Prior to randomization, patients underwent a clinical assessment and were divided into three groups based on diagnoses for bipolar disorder (n = 26 in both arms), depressive disorder (n = 26 in the treatment arm; n = 30 in the control arm) or other psychiatric disorders (n = 21 in the treatment arm; n = 27 in the control arm). Jollant and colleagues assessed the rate of suicidal remission with a confirmed score of three or less on a clinician-rated scale for suicidal ideation.
The median age of the patients was 40 years and 68% were women. The median score for suicidal ideation using the Beck Scale was 22. Severe suicidality occurred in 97.3% of patients in the treatment arm and 86.6% of patients in the control arm.
Remission of suicidal ideation
Overall, full remission of suicidal ideas at day 3 occurred among 63% of patients in the treatment arm compared with 31.6% of patients in the placebo arm (OR = 3.7; 95% CI, 1.9-7.3), according to Jollant and colleagues. The effect varied based on diagnosis. In the bipolar disorder group, 84.6% of patients who received ketamine achieved remission at day 3 compared with 28% of patients in the placebo arm (OR = 14.1; 95% CI, 3-92.2). For patients with a depressive disorder, 42.3% of patients in the treatment arm achieved remission compared with 35.7% of patients in the placebo arm (OR = 1.3; 95% CI, 0.3-5.2). For all other psychiatric disorders, 61.9% of patients in the treatment arm achieved remission compared with 30.8% of patients in the placebo arm (OR = 3.7; 95% CI, 0.9-17.3).
The significant benefit of ketamine diminished by week 6, with 69.5% of patients in the treatment arm achieving remission compared with 56.3% of patients in the control arm. However, adverse events associated with ketamine use were limited and no manic or psychotic symptoms were observed, according to the researchers. They also reported a mediating effect of mental pain in the treatment arm.
“While the short-term benefits of ketamine for the reduction of suicidal ideation are obvious and the short-term benefits-risk balance seems very favorable as shown in our study, the long-term benefits-risk balance will have to be determined with longer clinical trials,” Jollant said. “This includes the risk of addiction, and the benefits in terms of suicidal act.”
The treatment should only be used in hospital settings by experienced teams and should only be used in combination with other approaches like psychosocial support, he added.
Jollant and colleagues are also investigating the use of buprenorphine for the treatment of suicide.
A ‘new opioid-style crisis’
In a related editorial, Riccardo De Giorgi, MD, MRCPsych, a Wellcome Trust doctoral training fellow in biomedical and clinical sciences at the University of Oxford, noted addiction concerns, as “widespread use of ketamine might trigger a new opioid-style crisis.”
“Careful clinical consideration must precede any consideration of ketamine use,” he advised.
The findings from Jollant and colleagues emphasize how people with suicidal ideation are in “unbearable pain,” which brings into question whether a rapid treatment like ketamine should be available for them, according to De Giorgi.
“The possibility of an opioid-related mechanism of action for ketamine signals a need for caution, as well as restrictions on the duration of treatment,” he said.