Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Design of the Study
4.2. Data Analysis
4.3. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Adverse Reaction | Male Cases Number and % | Female Cases Number and % | Male and Female Cases | % of All ICSRs | Significance Level (P) |
---|---|---|---|---|---|
Increased blood pressure | 23 (53.5%) | 20 (46.5%) | 43 | 16.2% | 0.016410 * |
Dissociation/dissociative disorder | 14 (33.3%) | 28 (66.6%) | 42 | 15.8% | 0.802393 |
Suicidal ideation | 9 (34.6%) | 17 (65.4%) | 26 | 9.8% | 0.972193 |
Anxiety | 5 (21.7%) | 18 (78.3%) | 23 | 8.7% | 0.198565 |
Dizziness | 2 (11.1%) | 16 (88.9%) | 18 | 6.8% | 0.041125 * |
Completed suicide | 12 (70.6%) | 5 (29.4%) | 17 | 6.4% | 0.005334 * |
Drug ineffective | 5 (29.4%) | 12 (70.6%) | 17 | 6.4% | 0.685521 |
Suicide attempt | 3 (21.4%) | 11 (78.6%) | 14 | 5.0% | 0.369206 |
Loss of consciousness | 6 (46.1%) | 7 (53.8%) | 13 | 4.9% | 0.639931 |
Hallucination | 4 (33.3%) | 8 (66.7%) | 12 | 4.5% | 0.925157 |
Generalized tonic–clonic seizure | 4 (50.0%) | 4 (50.0%) | 8 | 3.0% | 0.653024 |
Diplopia | 2 (28.6%) | 5 (71.4%) | 7 | 2.6% | 0.977208 |
Aggression | 0 (0%) | 5 (100%) | 5 | 1.9% | N.A. |
Bradycardia | 4 (80.0%) | 1 (20%) | 5 | 1.9% | 0.112688 |
Adverse Reaction | Number and % of Serious ICSRs in the Age Group of 18–64 Years (N = 210) | Number and % of Serious ICSRs in the Age Group of 65–85 Years (N = 50) | Significance Level (P) |
---|---|---|---|
Increased blood pressure | 26 (12.4%) | 17 (34.0%) | 0.000490 * |
Dissociation/ dissociative disorder | 37 (17.6%) | 5 (10.0%) | 0.270536 |
Suicidal ideation | 23 (10.9%) | 3 (6.0%) | 0.431401 |
Anxiety | 20 (9.5%) | 3 (6.0%) | 0.608985 |
Dizziness | 12 (5.7%) | 6 (12.0%) | 0.206359 |
Completed suicide | 16 (7.6%) | 1 (2.0%) | 0.260073 |
Drug ineffective | 11 (5.2%) | 6 (12.0%) | 0.155604 |
Suicide attempt | 12 (5.7%) | 2 (4.0%) | 0.893348 |
Loss of consciousness | 10 (4.8%) | 3 (6.0%) | 1.0 |
Hallucination | 11 (5.2%) | 0 (0.0%) | N.A. |
Generalized tonic–clonic seizure | 5 (2.4%) | 2 (4.0%) | 0.881104 |
Diplopia | 6 (2.8%) | 1 (2.0%) | 0.881104 |
Aggression | 4 (1.9%) | 1 (2.0%) | 0.596922 |
Bradycardia | 4 (1.9%) | 1 (2.0%) | 0.596922 |
Cases and % of ICSRs (0–85 Years) (N = 265) | Cases and % of ICSRs (18–64 Years) (N = 210) | Cases and % of ICSRs (65–85 Years) (N = 50) | Male Cases and % of Total ICSRs (N = 265) | Female Cases and % of Total ICSRs (N = 265) | |
---|---|---|---|---|---|
Cases of death | 10 (3.8%) | 8 (3.8%) | 1 (2.0%) | 6 (2.3%) | 4 (1.5%) |
SOC | SARs to Esketamine | All Other SARs to Esketamine | SARs to Fluoxetine | All Other SARs to Fluoxetine | ROR Esketamine vs. Fluoxetine (95% C.I.) | SARs to Venlafaxine | All Other SARs to Venlafaxine | ROR Esketamine vs. Venlafaxine (95% C.I.) |
---|---|---|---|---|---|---|---|---|
Psychiatric disorders | 117 | 148 | 318 | 919 | 2.28 (1.74–3.00) | 573 | 1758 | 2.42 (1.87–3.15) |
Nervous system disorders | 26 | 239 | 371 | 695 | 0.20 (0.13–0.31) | 793 | 1226 | 0.17 (0.11–0.25) |
Vascular disorders | 23 | 242 | 66 | 1000 | 1.44 (0.88–2.36) | 156 | 1863 | 1.13 (0.72–1.79) |
Investigations | 18 | 247 | 119 | 947 | 0.58 (0.35–0.97) | 246 | 1773 | 0.52 (0.32–0.86) |
Respiratory, thoracic and mediastinal disorders | 14 | 251 | 76 | 990 | 0.73 (0.40–1.31) | 197 | 1822 | 0.51 (0.30–0.90) |
General disorders and administration site conditions | 14 | 251 | 240 | 826 | 0.19 (0.11–0.33) | 492 | 1527 | 0.17 (0.10–0.30) |
Cardiac disorders | 9 | 256 | 96 | 970 | 0.35 (0.18–0.71) | 258 | 1761 | 0.24 (0.12–0.47) |
Immune system disorders | 9 | 256 | 15 | 1051 | 2.46 (1.06–5.69) | 11 | 2008 | 6.42 (2.63–15.63) |
Gastrointestinal disorders | 7 | 258 | 147 | 919 | 0.18 (0.08–0.37) | 261 | 1758 | 0.18 (0.08–0.39) |
Adverse Reaction | Esketamine Cases/Not Cases Total Number of Cases = 265 | Fluoxetine Cases/Not Cases Total Number of Cases = 1066 | Venlafaxine Cases/Not Cases Total Number of Cases = 2019 | ROR Esketamine vs. Fluoxetine (95% C.I.) | ROR Esketamine vs. Venlafaxine (95% C.I.) | ROR Fluoxetine vs. Venlafaxine (95% C.I.) |
---|---|---|---|---|---|---|
Suicidal ideation | 26/239 | 38/1028 | 41/1978 | 2.94 (1.75–4.94) | 5.25 (3.15–8.73) | 1.78 (1.14–2.79) |
Suicide attempt | 14/251 | 70/996 | 102/1917 | 0.79 (0.44–1.43) | 1.05 (0.59–1.86) | 1.32 (0.96–1.81) |
Completed suicide | 17/248 | 9/1057 | 13/2006 | 8.05 (3.55–18.3) | 10.58 (5.08–22.04) | 1.31 (0.56–3.08) |
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Ammendolia, I.; Mannucci, C.; Esposito, E.; Calapai, G.; Currò, M.; Midiri, P.; Mondello, C.; Cardia, L.; Calapai, F. Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis. Pharmaceuticals 2025, 18, 702. https://doi.org/10.3390/ph18050702
Ammendolia I, Mannucci C, Esposito E, Calapai G, Currò M, Midiri P, Mondello C, Cardia L, Calapai F. Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis. Pharmaceuticals. 2025; 18(5):702. https://doi.org/10.3390/ph18050702
Chicago/Turabian StyleAmmendolia, Ilaria, Carmen Mannucci, Emanuela Esposito, Gioacchino Calapai, Mariaconcetta Currò, Paola Midiri, Cristina Mondello, Luigi Cardia, and Fabrizio Calapai. 2025. "Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis" Pharmaceuticals 18, no. 5: 702. https://doi.org/10.3390/ph18050702
APA StyleAmmendolia, I., Mannucci, C., Esposito, E., Calapai, G., Currò, M., Midiri, P., Mondello, C., Cardia, L., & Calapai, F. (2025). Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis. Pharmaceuticals, 18(5), 702. https://doi.org/10.3390/ph18050702