Emerging Trends in Drug-Induced Seizures: A Pilot Study

Document Type : Original Article

Authors

1 Department of Medical Sciences, Yazd Branch, Islamic Azad University, Yazd, Iran

2 Department of Forensic Medicine & Clinical Toxicology, Yazd Branch, Islamic Azad University, Yazd, Iran

3 Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Department of Forensic Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

5 Emergency medicine resident; Department of Emergency Medicine, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

6 Department of Pharmacology and Toxicology, School of Pharmacy, Iran University of Medical Sciences.

7 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

8 Department of Forensic Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

9 Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran

10 Students Research Committee, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Background: Seizures, indicative of uncontrolled and abnormal electrical activity in the brain, constitute a significant concern in emergency medicine.

Objectives: This pilot study, conducted in two toxicology centers in Yazd, Iran, aimed to enhance our understanding of drug-induced seizures (DIS).

Methods: This five-year cross-sectional study analyzed 205 cases in two toxicology centers in Yazd, Iran. The investigation focused on demographic distribution, causative agents, and clinical outcomes. Data entered into SPSS version 26 and analyzed. p<0.05 was assumed significant.

Results: Tramadol emerged as the predominant cause of DIS (74.15%), followed by benzodiazepine withdrawal (7.8%), organophosphorus toxins (3.41%), and methadone (3.41%). Tramadol ingestion was correlated with status epilepticus (Odds ratio (OR) = 4.166, 95% CI = 1.73-10.01), ICU admission (OR=3.394, CI = 1.623-7.1), and intubation (OR=0.057, CI = 0.012-0.272) P<0.05), but no significant correlation was observed between tramadol ingestion and overall outcome (P>0.05).  A significant correlation was found between ICU admission and age (P=0.04). Additionally, a notable correlation was seen between drug categories with outcome, status epilepticus, ICU admission, and intubation (P<0.05). Among five deaths, 2 (40%) were related to tramadol, 2 (40%) to organophosphorus compounds, and 1 (20%) to methadone.

Conclusion: Drug-induced seizures present critical challenges in emergency settings. Moreover, the widespread use of tramadol and a recent trend in its abuse have contributed to drug-induced seizures.  Organophosphorus toxins, though uncommon, led to severe complications and high mortality. Further research is essential to develop predictive models and refine clinical approaches in managing diverse drug-induced seizure scenarios.

Keywords


Acknowledgments: The present study was extracted from the doctoral dissertation of the first author in the field of psychology and was approved by the Ethics Committee of the Islamic Azad University of Shahrood with the ethics code IR.IAU.NEYSHABUR.REC.1399.004. The authors would like to express their great appreciation to the respected director of the Afarinesh Psychology Center in Neyshabur and all the participants who sincerely helped the researchers.

 

Availability of data and materials: Not applicable.

 

Conflicts of interest : The authors of the article declared no conflict of interest.

 

Consent for publication: Not applicable

 

Ethics approval and consent to participate: This study is based on a research project approved by Ethics Committee of Islamic Azad University of Shahrood with the code of ethics IR.IAU.NEYSHABUR.REC.1399.004. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable. Written informed consent was obtained from all participants.

 

Financial Disclosure: Not applicable

 

Author contributions: FS. AM, H.O, and H. Gh: Study design, data analysis, and drafting. F.F, R. A, and S. T: Study design, and critical reviewing. R. Sh. and M. Sh: Study design, critical reviewing. A.S. and SM.M, MA.TZ, A.F: Study design, Data acquisition, data analysis, and drafting the manuscript.

 

Open Access Policy: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

1. Huff JS, Murr N. Seizure. StatPearls. 2023;1-9.
 
2. Trinka E, Guerrini R, Shorvon S, Schachter S. Alcohol- and Toxin-Induced Seizures. In: The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children. 2nd ed. Cambridge: Cambridge University Press; 2019. 852-862.
https://doi.org/10.1017/9781108355209.118
 
3. Chen HY, Albertson TE, Olson KR. Treatment of drug-induced seizures. Br J Clin Pharmacol. 2016;81(3):412-9. doi: 10.1111/bcp.12720, ,[PMID: 26174744]
https://doi.org/10.1111/bcp.12720
PMid:26174744 PMCid:PMC4767205
 
4. Thundiyil JG, Rowley F, Papa L, et al. Risk factors for complications of drug-induced seizures. J Med Toxicol. 2011;7(1):16-23. doi: 10.1007/s13181-010-0096-4, [PMID: 20661684]
https://doi.org/10.1007/s13181-010-0096-4
PMid:20661684 PMCid:PMC3056005
 
5. Pesola GR, Avasarala J. Bupropion seizure proportion among new-onset generalized seizures and drug related seizures presenting to an emergency department. J Emerg Med. 2002;22(3):235-9. doi: 10.1016/s0736-4679(01)00474-7, [PMID]: 11932084
https://doi.org/10.1016/S0736-4679(01)00474-7
PMid:11932084
 
6. Fletcher ML, Sarangarm P, Nash J, Smolinske SC, Alunday RL, Seifert SA, et al. A systematic review of second line therapies in toxic seizures. Clin Toxicol. 2021;59(6):451-6. doi: 10.1080/15563650.2021.1894332, [PMID: 33755521].
https://doi.org/10.1080/15563650.2021.1894332
PMid:33755521
 
7. Reichert C, Reichert P, Monnet-Tschudi F, Kupferschmidt H, Ceschi A, Rauber-Lüthy C. Seizures after single-agent overdose with pharmaceutical drugs: analysis of cases reported to a poison center. Clin Toxicol (Phila). 2014;52(6):629-34. doi: 10.3109/15563650.2014.918627, [PMID]: 24844578
https://doi.org/10.3109/15563650.2014.918627
PMid:24844578
 
8. Trinka E, Guerrini R, Shorvon S, Schachter S. Recreational and Illicit Drugs Causing Seizures and Epilepsy. In: The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children. 2nd ed. Cambridge: Cambridge University Press; 2019. 848-851.
https://doi.org/10.1017/9781108355209.117
 
9. Thundiyil JG, Kearney TE, Olson KR. Evolving epidemiology of drug-induced seizures reported to a Poison Control Center System. J Med Tixicol. 2007;3:15-9. doi: 10.1007/BF03161033,[ PMID: 18072153]
https://doi.org/10.1007/BF03161033
PMid:18072153 PMCid:PMC3550124
 
10. Okazi A, Taghaddosinejad F, Mazrouei N, Forouzeh M, Barzegar A, Fallah F. Occurrence and recurrence of seizures and related factors in patients with tramadol ingestion. Int J Med Toxicol Forensic Med. 2018;8(3):101-8. [PMID: 31432038].
 
11. Behnoush B, Taghadosinejad F, Arefi M, Shahabi M, Jamalian M, Kazemifar AM. Prevalence and complications of drug-induced seizures in Baharloo Hospital, Tehran, Iran. Iranian J Toxicol. 2012;6(16):588-93.
 
12. Trinka E, Guerrini R, Shorvon S, Schachter S, editors. Drug-Induced Seizures. In: The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children. 2nd ed. Cambridge: Cambridge University Press 2019; 839-847.
https://doi.org/10.1017/9781108355209.116
 
13. Messing RO, Closson RG, Simon RP. Drug-induced seizures: a 10-year experience. Neurology. 1984;34(12):1582-6. doi: 10.1212/wnl.34.12.1582, [PMID: 6504330].
https://doi.org/10.1212/WNL.34.12.1582
PMid:6504330
 
14. Haque B. Characteristics of epilepsy patients at a tertiary care hospital in Bangladesh. Research. 2014;2014;1:741:741.
https://doi.org/10.13070/rs.en.1.741
 
15. Guidelines for intensive care unit admission, discharge, and triage. Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. Crit Care Med. 1999;27(3):633-8.
https://doi.org/10.1097/00003246-199903000-00048
PMid:10199547
 
16. Lapostolle F, Alhéritière A. To intubate or not intubate, that is still the question. European J Emerge Med. 2020;27(5):387-8.
https://doi.org/10.1097/MEJ.0000000000000726
PMid:32516162
 
17. Wylie T, Sandhu DS, Murr NI. Status Epilepticus. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from:https://www.ncbi.nlm.nih.gov/books/NBK430686.
 
18. Jovanović-Čupić V, Martinović Ž, Nešić N. Seizures associated with intoxication and abuse of tramadol. Clin toxicol. 2006;44(2):143-6.
https://doi.org/10.1080/1556365050014418
PMid:16615669
 
19. Izadi mood N YA, Gheshlaghi F, Mojiri R. Causes, treatments and outcome of seizure in drugs and toxins intoxicated patients. J Tehran Univ MEd SCi 2009; 66 (3): 214-20.
 
20. Nakhaee S, Amirabadizadeh A, Brent J, Miri-Moghaddam E, Foadoddini M, Farrokhfall K, Hosseini M, Abdollahi M, Mehrpour O. Tramadol and the occurrence of seizures: a systematic review and meta-analysis. Critt Rev 2019;4;49(8):710-23. doi: 10.1080/10408444.2019.1694861
https://doi.org/10.1080/10408444.2019.1694861
PMid:31914355
 
21. Boostani R, Derakhshan S. Tramadol induced seizure: A 3-year study. Caspian J int Med. 2012;3(3):484.[ PMID: 24009919].
 
22. Ryan NM, Isbister GK. Tramadol overdose causes seizures and respiratory depression but serotonin toxicity appears unlikely. Clin toxicol. 2015;53(6):545-50. doi.org/10.3109/15563650.2015.1036279, [PMID: 31914355].
https://doi.org/10.3109/15563650.2015.1036279
PMid:25901965
 
23. Shapiro MJ, Cole AJ. Alcohol-and toxin-induced seizures. This page intentionally left blank.674.
https://doi.org/10.1017/CBO9780511921001.097
 
24. Olson KR, Kearney TE, Dyer JE, Benowitz NL, Blanc PD. Seizures associated with poisoning and drug overdose. American J Emerg Med. 1994;12(3):392-94. doi: 10.1016/0735-6757(93)90001-r [PMID: 8192750].
https://doi.org/10.1016/0735-6757(93)90001-R
PMid:8192750