Drug Safety

, Volume 39, Issue 4, pp 307–321 | Cite as

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

  • Marlene Bloechliger
  • Alessandro Ceschi
  • Stephan Rüegg
  • Hugo Kupferschmidt
  • Stephan Kraehenbuehl
  • Susan S. Jick
  • Christoph R. Meier
  • Michael Bodmer
Original Research Article



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.


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.


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.


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.


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.


Depressed Patient Venlafaxine Index Date Duloxetine Mirtazapine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Pascal Egger (Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland) for the programming and technical support.

Compliance with Ethical Standards


No sources of funding were used to assist in the preparation of this study.

Conflict of interest

Marlene Bloechliger, Alessandro Ceschi, Stephan Rueegg, Hugo Kupferschmidt, Stephan Kraehenbuehl, Susan S. Jick, Christoph R. Meier, and Michael Bodmer have no conflicts of interest that are directly related to the content of this study.

Authors’ contributions

Study conception and design: Marlene Bloechliger, Alessandro Ceschi, Stephan Rueegg, Hugo Kupferschmidt, Stephan Kraehenbuehl, Susan S. Jick, Christoph R. Meier, and Michael Bodmer. Acquisition of data, guarantors for the study: Susan S. Jick and Christoph R. Meier. Analysis and interpretation of data: Marlene Bloechliger, Christoph R. Meier, Michael Bodmer. Drafting the manuscript: Marlene Bloechliger. Editing the manuscript: Alessandro Ceschi, Stephan Rueegg, Hugo Kupferschmidt, Stephan Kraehenbuehl, Susan S. Jick, Christoph R. Meier, and Michael Bodmer.

Supplementary material

40264_2015_363_MOESM1_ESM.pdf (384 kb)
Supplementary material 1 (PDF 385 kb)


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Marlene Bloechliger
    • 1
  • Alessandro Ceschi
    • 2
    • 3
  • Stephan Rüegg
    • 4
  • Hugo Kupferschmidt
    • 2
  • Stephan Kraehenbuehl
    • 5
  • Susan S. Jick
    • 6
  • Christoph R. Meier
    • 1
    • 6
    • 7
  • Michael Bodmer
    • 1
    • 8
  1. 1.Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, Basel Pharmacoepidemiology UnitUniversity of BaselBaselSwitzerland
  2. 2.National Poisons Centre, Tox Info SuisseAssociated Institute of the University of ZurichZurichSwitzerland
  3. 3.Division of Clinical Pharmacology and Toxicology, Department of Internal MedicineEnte Ospedaliero Cantonale LuganoLuganoSwitzerland
  4. 4.Division of Clinical Neurophysiology, Department of NeurologyUniversity Hospital BaselBaselSwitzerland
  5. 5.Division of Clinical Pharmacology and Toxicology, Department of Pharmaceutical SciencesUniversity of BaselBaselSwitzerland
  6. 6.Boston Collaborative Drug Surveillance ProgramBoston University School of Public HealthLexingtonUSA
  7. 7.Hospital PharmacyUniversity Hospital BaselBaselSwitzerland
  8. 8.Medical DepartmentZuger KantonsspitalZugSwitzerland

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