A new study in BMJ challenges the notion that ketamine has anti-suicidal effects. In this randomized, controlled trial, the researchers found that ketamine was no better than placebo for reducing suicidal ideation (thoughts/intent) in depression.
Ketamine did beat placebo for bipolar disorder—but only in the short-term. By the 6-week follow-up, ketamine was no better than placebo for bipolar disorder either.
One participant died by suicide in the ketamine group versus none in the placebo group. The rates of suicide attempts were about the same in both the ketamine group and the placebo group.
Mocrane Abbar led the study at the University of Montpellier, Nîmes, France. It included 156 patients who were hospitalized for suicidal ideation. Fifty-two had a diagnosis of bipolar disorder, 56 had a diagnosis of depression, and 48 had other diagnoses (e.g., PTSD, anxiety disorders, dysthymia).
They were randomly assigned to receive either two ketamine infusions (24 hours apart) or two saline infusions (the placebo control condition). About 88% of the participants had attempted suicide in the past.
The main outcome was whether participants had suicidal thoughts 72 hours after their last injection.
For those with bipolar disorder, the drug appeared to have a strong short-term effect: 84.6% of those who received ketamine versus 28.0% of those who received placebo no longer had suicidal thoughts.
However, ketamine was no different from placebo (statistically speaking) for those with depression or other diagnoses. About the same number of people in these groups continued to have suicidal thoughts.
One suicide attempt occurred during the first 72 hours—and it was someone who took the active drug, not a placebo.
Rates of suicide attempts during the next six weeks were not statistically different between those who took a placebo and those who took ketamine, meaning that the drug did not actually stop people from attempting suicide over that time, even for those with bipolar disorder.
Over the remainder of the study, one person died by suicide after taking ketamine. According to the authors, this was “determined by the oversight committee to be unrelated to the intervention.”
It is unclear how death by suicide—in a trial to determine if a treatment prevents suicidal thoughts—could be considered “unrelated to the intervention.”
The findings of this study challenge the commonly-held idea that ketamine is particularly effective for depression and specifically at preventing suicide in those with depression.
In an accompanying editorial, Riccardo De Giorgi at the University of Oxford makes this point:
The study “perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine.”
He adds, “In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder.”
Despite finding that ketamine was ineffective for both depression and other disorders, that the effects even for bipolar disorder were temporary, and that it did not reduce actual suicide attempts, Abbas and his co-researchers conclude that “the findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients.”
The researchers had financial ties to the pharmaceutical industry, including companies that market ketamine and its derivatives:
Support from PHRC-N 2013 for the submitted work; FJ has no declaration of interests for the past five years. PG received, during the past five years, fees for presentations at congresses or participation in scientific boards from Alcediag-Alcen, Angelini, GSK, Janssen, Lundbeck, Otsuka, SAGE, and Servier. WE-H reports personal fees from EISAI, Janssen, Lundbeck, Otsuka, UCB, and Chugai. PC received speaker and consultation fees from Exeltis, Janssen, and Pfizer. GV is part of a scientific board for Janssen. RG has received compensation as a member of the scientific advisory board of Janssen, Lundbeck, Roche, SOBI, and Takeda; he has served as consultant and/or speaker for Astra Zeneca, Boehringer-Ingelheim, Pierre Fabre, Lilly, Lundbeck, MAPREG, Otsuka, Pileje, SANOFI, Servier, LVMH and received compensation; and he has received research support from Servier; cofounder and stock shareholder: Regstem. P-ML has received compensation as consultant and member of a scientific advisory board for Janssen. LS declares fees for advisory board, travel support activities of consultant and lecturer in the past five years received from Janssen, Lundbeck, and Otsuka; fees for advisory board, travel support activities of consultant, lecturer, and faculty member in the past five years received from Eisai, Janssen, Lundbeck, Otsuka, Sanofi, Teva. MA declares fees from Astra Zeneca and Lundbeck, and has been invited to congresses by Janssen-Cilag, Otsuka, Lundbeck, Servier, and Astra Zeneca.
Abbar, M., Demattei, C., El-Hage, W., Llorca, P-M., Samalin, L., Demaricourt, P., . . . & Jollant, F. (2022). Ketamine for the acute treatment of severe suicidal ideation: Double-blind, randomized placebo-controlled trial. BMJ, 376, e067194. https://doi.org/10.1136/bmj-2021-067194 (Link)
De Giorgi, R. (2022). Ketamine for suicidal ideation. BMJ, 376, o74. https://doi.org/10.1136/bmj.o74 (Link)