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Cited by 40Epilepsy research and treatmentTreatment of Major DepressionElectroconvulsive Therapy Studies

Risk of Seizures Associated with Antidepressant Use in Patients with Depressive Disorder: Follow-up Study with a Nested Case–Control Analysis Using the Clinical Practice Research Datalink

Bloechliger, Marlene, Ceschi, Alessandro, Rüegg, Stephan, Kupferschmidt, Hugo, Kraehenbuehl, Stephan, Jick, Susan S., Meier, Christoph R., Bodmer, Michael·2016·Drug Safety
DOI 10.1007/s40264-015-0363-z
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Abstract

Introduction Antidepressant use has been associated with an increased risk of seizures. Evidence on the association between antidepressant use at therapeutic doses and seizures mainly comes from clinical trials that were not designed to investigate this potential relationship.Objective The objective of this study was to assess the risk of first-time seizures in association with exposure to antidepressants in patients with depressive disorders.Methods We conducted a retrospective follow-up study with a nested case-control analysis between 1998 and 2012, using data from the UK-based Clinical Practice Research Datalink (CPRD). We estimated crude incidence rates with 95 % confidence intervals (CIs) of seizures in depressed patients who used selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), 'other antidepressants', no antidepressants, or who had used antidepressants in the past. To adjust for potential confounding, we estimated odds ratios of antidepressant drug use among cases with seizures and matched controls in a nested case-control analysis.Results Of 151,005 depressed patients, 619 had an incident seizure during follow-up. Incidence rates per 10,000 person-years were 12.44 (95 % CI 10.67-14.21) in SSRI users, 15.44 (95 % CI 8.99-21.89) in SNRI users, 8.33 (95 % CI 4.68-11.98) in TCA users, 9.33 (95 % CI 6.19-12.46) in non-users of antidepressants, and 5.05 (95 % CI 4.49-5.62) in past users of antidepressants. In the case-control analysis, relative risk estimates for seizures were increased in current users of SSRIs (adjusted odds ratio 1.98, 95 % CI 1.48-2.66) and SNRIs (adjusted odds ratio 1.99, 95 % CI 1.20-3.29), but not TCAs (adjusted odds ratio 0.99, 95 % CI 0.63-1.53), compared with non-users.Conclusion Current use of SSRIs or SNRIs was associated with a twofold increased risk of first-time seizures compared with non-use, while current use of TCAs (mostly low dose) was not associated with seizures. Treatment initiation in SSRI and SNRI users was associated with a higher risk of seizures than longer-term treatment.

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Authors
Bloechliger, M., Ceschi, A., Rüegg, S., Kupferschmidt, H., Kraehenbuehl, S., Jick, S. S., Meier, C. R., & Bodmer, M.
Affiliations
  • University of Basel (CH)
  • University of Zurich (CH)
  • Boston University (US)
Corresponding author
Meier, Christoph R.
ORCID
Venue
Drug Safety
Publisher
Springer Science and Business Media LLC
Published
2015-12-09
Volume
39
Issue
4
Pages
307-321
ISSN
  • 0114-5916 (ISSN-L)
  • 1179-1942
DOI
10.1007/s40264-015-0363-z
OpenAlex
W2196017155
Cited by
40
References
41
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 5 · 2017: 14 · 2016: 2
FWCI
5.68
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Drug Safety (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords
depressive disorders, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, seizure risk, antidepressant safety, Clinical Practice Research Datalink, incidence rates, confounding adjustment, adverse drug reactions, depression pharmacotherapy, anticonvulsant prophylaxis, antipsychotic prophylaxis
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Antidepressive Agents, Depressive Disorder, Female, Follow-Up Studies, Humans, Male, Middle Aged, Retrospective Studies, Seizures, Switzerland, Case-Control Studies, Young Adult, Electronic Health Records, Databases, Pharmaceutical

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