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Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits.
BMJ Open. 2019 03 13; 9(3):e026705.BO

Abstract

OBJECTIVES

Tramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. While seizures have been reported with its use, the risk in clinical practice has not been well characterised. We examined risk of seizure with tramadol relative to codeine, a comparable opioid analgesic.

DESIGN

Retrospective nested case-control study. For each case, we identified up to 10 controls matched on age, sex, US state of residence and date of cohort entry (±365 days). We calculated ORs to determine the association between seizure and exposure to tramadol, codeine (≥15 mg), both or neither, in the preceding 30 days.

SETTING

Cohort of patients, who had continuous health coverage and resided in the same state for≥3 years, identified from linked administrative health data in US MarketScan databases from 2009 to 2012.

PARTICIPANTS

We identified 96 753 patients with seizure and 888 540 matched controls.

PRIMARY AND SECONDARY OUTCOME MEASURES

In the primary analysis, we defined cases using a broad definition of seizure (based on either an outpatient physician claim for seizure disorder or a seizure-related emergency department visit or hospitalisation). In a secondary analysis, we used a more specific definition of seizure restricted to a hospital visit with a principal diagnosis of seizure.

RESULTS

In the primary analysis, we found no association between risk of seizure and exposure to tramadol compared with codeine (OR 1.03, 95% CI 0.93 to 1.15). However, in the secondary analysis (using a more specific definition of seizure), this association was statistically significant (OR 1.41, 95% CI 1.11 to 1.79).

CONCLUSIONS

Tramadol was not associated with an increased risk of seizure defined by inpatient and outpatient diagnoses. However, this finding was sensitive to the outcome definition used and requires further study.

Authors+Show Affiliations

Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Victoria, British Columbia, Canada.Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Victoria, British Columbia, Canada.Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.Applied Health Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.Clinical Pharmacology and Toxicology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30872555

Citation

Morrow, Richard L., et al. "Tramadol and the Risk of Seizure: Nested Case-control Study of US Patients With Employer-sponsored Health Benefits." BMJ Open, vol. 9, no. 3, 2019, pp. e026705.
Morrow RL, Dormuth CR, Paterson M, et al. Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits. BMJ Open. 2019;9(3):e026705.
Morrow, R. L., Dormuth, C. R., Paterson, M., Mamdani, M. M., Gomes, T., & Juurlink, D. N. (2019). Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits. BMJ Open, 9(3), e026705. https://doi.org/10.1136/bmjopen-2018-026705
Morrow RL, et al. Tramadol and the Risk of Seizure: Nested Case-control Study of US Patients With Employer-sponsored Health Benefits. BMJ Open. 2019 03 13;9(3):e026705. PubMed PMID: 30872555.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits. AU - Morrow,Richard L, AU - Dormuth,Colin R, AU - Paterson,Michael, AU - Mamdani,Muhammad M, AU - Gomes,Tara, AU - Juurlink,David N, AU - ,, Y1 - 2019/03/13/ PY - 2019/3/16/entrez PY - 2019/3/16/pubmed PY - 2020/4/14/medline KW - adverse events KW - case control study KW - opioids KW - seizure KW - tramadol SP - e026705 EP - e026705 JF - BMJ open JO - BMJ Open VL - 9 IS - 3 N2 - OBJECTIVES: Tramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. While seizures have been reported with its use, the risk in clinical practice has not been well characterised. We examined risk of seizure with tramadol relative to codeine, a comparable opioid analgesic. DESIGN: Retrospective nested case-control study. For each case, we identified up to 10 controls matched on age, sex, US state of residence and date of cohort entry (±365 days). We calculated ORs to determine the association between seizure and exposure to tramadol, codeine (≥15 mg), both or neither, in the preceding 30 days. SETTING: Cohort of patients, who had continuous health coverage and resided in the same state for≥3 years, identified from linked administrative health data in US MarketScan databases from 2009 to 2012. PARTICIPANTS: We identified 96 753 patients with seizure and 888 540 matched controls. PRIMARY AND SECONDARY OUTCOME MEASURES: In the primary analysis, we defined cases using a broad definition of seizure (based on either an outpatient physician claim for seizure disorder or a seizure-related emergency department visit or hospitalisation). In a secondary analysis, we used a more specific definition of seizure restricted to a hospital visit with a principal diagnosis of seizure. RESULTS: In the primary analysis, we found no association between risk of seizure and exposure to tramadol compared with codeine (OR 1.03, 95% CI 0.93 to 1.15). However, in the secondary analysis (using a more specific definition of seizure), this association was statistically significant (OR 1.41, 95% CI 1.11 to 1.79). CONCLUSIONS: Tramadol was not associated with an increased risk of seizure defined by inpatient and outpatient diagnoses. However, this finding was sensitive to the outcome definition used and requires further study. SN - 2044-6055 UR - https://www.unboundmedicine.com/medline/citation/30872555/Tramadol_and_the_risk_of_seizure:_nested_case-control_study_of_US_patients_with_employer-sponsored_health_benefits L2 - http://bmjopen.bmj.com/cgi/pmidlookup?view=long&pmid=30872555 DB - PRIME DP - Unbound Medicine ER -