Association between tramadol use and seizures:   A nationwide case-case-time-control study

Sohee Park; Hyesung Lee; Ju Hwan Kim; Ha-Lim Jeon; Ju-Young Shin

doi:10.1002/pds.5417

Association between tramadol use and seizures: A nationwide case-case-time-control study

Sohee Park, Hyesung Lee, Ju Hwan Kim, Ha-Lim Jeon, Ju-Young Shin

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: Tramadol may lower the seizure threshold; however, there is no conclusive evidence to confirm this. This study aimed to determine whether the use of tramadol is associated with the occurrence of seizures.

METHODS: We conducted a case-case-time-control (CCTC) study by identifying patients who had received tramadol and seizure diagnosis in a nationwide healthcare database in South Korea between 2003 and 2015. Each case was matched for age and sex to one future case to adjust for time trends in exposure without selection bias from the use of an external control group. The use of tramadol was assessed during a risk period of 1-30 days, and two reference periods, 61-90 days and 91-120 days, preceding the first diagnosis of seizures. We calculated the adjusted odds ratio (aOR) by dividing the OR in cases (case-crossover) by the OR in future cases (control-crossover). We performed a dose-response analysis using the average daily dose.

RESULTS: We identified 2523 incident cases with matched future cases (mean age, 45.4 years; 50% men). The aOR for seizure with tramadol use was 0.94 (95% confidence interval [CI], 0.98-1.43) in the CCTC analysis, with a case-crossover OR of 1.19 (0.98-1.43) and control-crossover OR of 1.27 (1.03-1.56). The dose-response analysis showed a similar trend in the main analysis: a low-dose aOR of 0.80 (0.50-1.28) and a high-dose aOR of 0.92 (0.41-2.11).

CONCLUSION: We could not identify a significant association between transient use of tramadol and incidence of seizures in clinical practice.

Original language	English
Pages (from-to)	614-622
Number of pages	9
Journal	Pharmacoepidemiology and Drug Safety
Volume	31
Issue number	6
Early online date	9 Feb 2022
DOIs	https://doi.org/10.1002/pds.5417
Publication status	Published - 2 May 2022

Bibliographical note

Keywords

Analgesics, Opioid/adverse effects
Case-Control Studies
Cross-Over Studies
Female
Humans
Male
Middle Aged
Odds Ratio
Seizures/chemically induced
Tramadol/adverse effects

Access to Document

10.1002/pds.5417

Supporting Information_revised Association between tramadol use and seizures
This is the supporting information of the following article: Park et al (2022) 'Association between tramadol use and seizures: A nationwide case–case-time-control study' in Pharmacoepidemiology & Drug Safety, which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/pds.5417. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Accepted author manuscript, 315 KB
Manuscript_revised clean Association between tramadol use and seizures
This is the peer reviewed version of the following article: Park et al (2022) 'Association between tramadol use and seizures: A nationwide case–case-time-control study' in Pharmacoepidemiology & Drug Safety, which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/pds.5417. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Accepted author manuscript, 146 KB

Cite this

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title = "Association between tramadol use and seizures: A nationwide case-case-time-control study",

abstract = "PURPOSE: Tramadol may lower the seizure threshold; however, there is no conclusive evidence to confirm this. This study aimed to determine whether the use of tramadol is associated with the occurrence of seizures.METHODS: We conducted a case-case-time-control (CCTC) study by identifying patients who had received tramadol and seizure diagnosis in a nationwide healthcare database in South Korea between 2003 and 2015. Each case was matched for age and sex to one future case to adjust for time trends in exposure without selection bias from the use of an external control group. The use of tramadol was assessed during a risk period of 1-30 days, and two reference periods, 61-90 days and 91-120 days, preceding the first diagnosis of seizures. We calculated the adjusted odds ratio (aOR) by dividing the OR in cases (case-crossover) by the OR in future cases (control-crossover). We performed a dose-response analysis using the average daily dose.RESULTS: We identified 2523 incident cases with matched future cases (mean age, 45.4 years; 50% men). The aOR for seizure with tramadol use was 0.94 (95% confidence interval [CI], 0.98-1.43) in the CCTC analysis, with a case-crossover OR of 1.19 (0.98-1.43) and control-crossover OR of 1.27 (1.03-1.56). The dose-response analysis showed a similar trend in the main analysis: a low-dose aOR of 0.80 (0.50-1.28) and a high-dose aOR of 0.92 (0.41-2.11).CONCLUSION: We could not identify a significant association between transient use of tramadol and incidence of seizures in clinical practice.",

keywords = "Analgesics, Opioid/adverse effects, Case-Control Studies, Cross-Over Studies, Female, Humans, Male, Middle Aged, Odds Ratio, Seizures/chemically induced, Tramadol/adverse effects",

author = "Sohee Park and Hyesung Lee and Kim, {Ju Hwan} and Ha-Lim Jeon and Ju-Young Shin",

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T1 - Association between tramadol use and seizures

T2 - A nationwide case-case-time-control study

AU - Park, Sohee

AU - Lee, Hyesung

AU - Kim, Ju Hwan

AU - Jeon, Ha-Lim

AU - Shin, Ju-Young

PY - 2022/5/2

Y1 - 2022/5/2

N2 - PURPOSE: Tramadol may lower the seizure threshold; however, there is no conclusive evidence to confirm this. This study aimed to determine whether the use of tramadol is associated with the occurrence of seizures.METHODS: We conducted a case-case-time-control (CCTC) study by identifying patients who had received tramadol and seizure diagnosis in a nationwide healthcare database in South Korea between 2003 and 2015. Each case was matched for age and sex to one future case to adjust for time trends in exposure without selection bias from the use of an external control group. The use of tramadol was assessed during a risk period of 1-30 days, and two reference periods, 61-90 days and 91-120 days, preceding the first diagnosis of seizures. We calculated the adjusted odds ratio (aOR) by dividing the OR in cases (case-crossover) by the OR in future cases (control-crossover). We performed a dose-response analysis using the average daily dose.RESULTS: We identified 2523 incident cases with matched future cases (mean age, 45.4 years; 50% men). The aOR for seizure with tramadol use was 0.94 (95% confidence interval [CI], 0.98-1.43) in the CCTC analysis, with a case-crossover OR of 1.19 (0.98-1.43) and control-crossover OR of 1.27 (1.03-1.56). The dose-response analysis showed a similar trend in the main analysis: a low-dose aOR of 0.80 (0.50-1.28) and a high-dose aOR of 0.92 (0.41-2.11).CONCLUSION: We could not identify a significant association between transient use of tramadol and incidence of seizures in clinical practice.

AB - PURPOSE: Tramadol may lower the seizure threshold; however, there is no conclusive evidence to confirm this. This study aimed to determine whether the use of tramadol is associated with the occurrence of seizures.METHODS: We conducted a case-case-time-control (CCTC) study by identifying patients who had received tramadol and seizure diagnosis in a nationwide healthcare database in South Korea between 2003 and 2015. Each case was matched for age and sex to one future case to adjust for time trends in exposure without selection bias from the use of an external control group. The use of tramadol was assessed during a risk period of 1-30 days, and two reference periods, 61-90 days and 91-120 days, preceding the first diagnosis of seizures. We calculated the adjusted odds ratio (aOR) by dividing the OR in cases (case-crossover) by the OR in future cases (control-crossover). We performed a dose-response analysis using the average daily dose.RESULTS: We identified 2523 incident cases with matched future cases (mean age, 45.4 years; 50% men). The aOR for seizure with tramadol use was 0.94 (95% confidence interval [CI], 0.98-1.43) in the CCTC analysis, with a case-crossover OR of 1.19 (0.98-1.43) and control-crossover OR of 1.27 (1.03-1.56). The dose-response analysis showed a similar trend in the main analysis: a low-dose aOR of 0.80 (0.50-1.28) and a high-dose aOR of 0.92 (0.41-2.11).CONCLUSION: We could not identify a significant association between transient use of tramadol and incidence of seizures in clinical practice.

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KW - Case-Control Studies

KW - Cross-Over Studies

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Odds Ratio

KW - Seizures/chemically induced

KW - Tramadol/adverse effects

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U2 - 10.1002/pds.5417

DO - 10.1002/pds.5417

M3 - Article

C2 - 35141978

SN - 1053-8569

VL - 31

SP - 614

EP - 622

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

IS - 6

ER -