The association between ketamine and esketamine and suicidality: reports to the Food And Drug Administration Adverse Event Reporting System (FAERS).
Roger S McIntyre, Rodrigo B Mansur, Joshua D Rosenblat, Kayla M Teopiz, Angela T H Kwan
Expert opinion on drug safety June 21, 2024 DOI: 10.1080/14740338.2024.2368827 via PubMed
Summary
AI-generated from the abstractKetamine and esketamine reduce measures of suicidality in people with treatment-resistant depression, but whether they can worsen preexisting suicidality is unclear. Analysis of the FDA Adverse Event Reporting System from 1970 and 2019 through September 2023 found higher reporting odds ratios for suicidal ideation (7.58) and depression suicidal (14.19) with esketamine compared to lithium. In contrast, lower reporting odds ratios for suicide attempt were observed with both ketamine (0.15) and esketamine (0.57). The mixed results across different aspects of suicidality prevent any determination of causal effects, and the lower odds for suicide attempt cannot be interpreted as a direct therapeutic effect.
Study at a glance
| Characteristics | Pharmacovigilance analysis Peer reviewed |
|---|---|
| Population | Reports in the FDA Adverse Event Reporting System (FAERS) database |
| Interventions | Ketamine Esketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Suicidality Depression treatment Suicide prevention Ketamine therapy |
| Citations | 7 |
| Key finding | Esketamine was associated with higher reporting odds for suicidal ideation and depression suicidal, while both ketamine and esketamine were associated with lower reporting odds for suicide attempt. |
Abstract
Replicated evidence indicates that ketamine and esketamine reduce measures of suicidality in persons with treatment-resistant depression (TRD). It remains uncertain whether individuals experience worsening of preexisting suicidality with either agent. The Food and Drug Administration Adverse Event Reporting System (FAERS) database was searched from 1970 and 2019 to 30 September 2023 for reports of suicidal ideation, depression suicidal, suicidal behavior, suicidal attempt, and completed suicide in association with ketamine and esketamine exposure, respectively. We present reporting odds ratios (ROR) significance was determined when the lower limit of the 95% confidence interval (CI) exceeded 1.0. Lithium was used as the control agent. Observed a higher ROR for suicidal ideation (ROR 7.58, 95% CI 6.34-9.07) and depression suicidal (ROR 14.19, 95% CI 1.80-112.07) with esketamine. Significantly lower RORs were observed for suicide attempt with ketamine (ROR 0.15, 95% CI 0.11-0.21) and esketamine (ROR 0.57, 95% CI 0.48-0.67). Mixed RORs across aspects of suicidality were observed with ketamine and esketamine. Limitations of the FAERS database prevent any determination of causal effects new onset suicidality to either agent. The lower RORs for suicide attempt with ketamine and esketamine is noted but cannot be interpreted as a direct therapeutic effect.