Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial

Abstract

Objective To confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group. Design Prospective, double blind, superiority, randomised placebo controlled trial. Setting Seven French teaching hospitals between 13 April 2015 and 12 March 2019. Eligibility criteria for participants Aged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine. Participants 156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders. Intervention Two 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment. Main outcome measures The primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3. Analyses were conducted on an intention-to-treat basis. Results More participants receiving ketamine reached full remission of suicidal ideas at day 3 than those receiving placebo: 46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm (odds ratio 3.7 (95% confidence interval 1.9 to 7.3), P<0.001). This effect differed according to the diagnosis (treatment: P<0.001; interaction: P=0.02): bipolar (odds ratio 14.1 (95% confidence interval 3.0 to 92.2), P<0.001), depressive (1.3 (0.3 to 5.2), P=0.6), or other disorders (3.7 (0.9 to 17.3, P=0.07)). Side effects were limited. No manic or psychotic symptom was seen. Moreover, a mediating effect of mental pain was found. At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5% v 56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7). Conclusions The findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients. Comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain might explain the anti-suicidal effects of ketamine. Trial registration ClinicalTrials.gov NCT02299440 .

Interventions for attempted suicide

“…No trials have examined effectiveness of ketamine in preventing further suicide-related events in attempted suicide. Two randomised double-blind, placebo-controlled trials found short-term benefits, extending over days to weeks, for rapid reduction in suicidal ideation [12,13 ▪ ]. Two important findings were that the positive benefits of ketamine extended to 6 weeks and patients with bipolar disorder, but not major depression, benefited from the treatment [13 ▪ ].…”

“…Two randomised double-blind, placebo-controlled trials found short-term benefits, extending over days to weeks, for rapid reduction in suicidal ideation [12,13 ▪ ]. Two important findings were that the positive benefits of ketamine extended to 6 weeks and patients with bipolar disorder, but not major depression, benefited from the treatment [13 ▪ ]. No differences were noted in safety outcomes, such as exacerbations of psychosis, dissociative symptoms, and addiction potential.…”

Ketamine for suicidal ideation: heed lessons from opiate epidemic

“…This study by Abbar and colleagues shows that the use of ketamine reduces suicidal thoughts, although not suicide attempts, in bipolar depression for several weeks compared with treatment as usual 1. It seems to show that ordinary psychosocial induced (major) depression does not respond to ketamine and that bipolar depression does, highlighting their essential biological differences—one being a disorder of mood induced by life events and losses and the other being a mood disorder of genetic provenance probably more biochemically based.…”

Ketamine for suicidal ideation

“…In this context, the linked study by Abbar and colleagues (doi:10.1136/bmj-2021-067194)7 is set to challenge some of our current insights about ketamine. This randomised placebo controlled trial investigated the anti-suicidal effects of intravenous ketamine from three days to six weeks after treatment in 156 patients voluntarily admitted to hospital with severe suicidal ideation.…”

“…This is hard to say, given the plausible concern that the widespread use of ketamine might trigger a new opioid style crisis 10. Whether ketamine reduces suicidal ideation in some people is a matter of evidence—which this trial by Abbar and colleagues provides 7. But whether the emergency use of ketamine for suicidal crises will be recommended in practice depends on many other factors, including the values and preferences of patients, clinicians, researchers, and policymakers.…”