title: 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.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, Basel Pharmacoepidemiology Unit, University of Basel, Basel, Switzerland.
authors.forename: Marlene
authors.initials: M
authors.lastname: Bloechliger
authors.affiliation: National Poisons Centre, Tox Info Suisse, Associated Institute of the University of Zurich, Zurich, Switzerland.|Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, Ente Ospedaliero Cantonale Lugano, Lugano, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ceschi
authors.affiliation: Division of Clinical Neurophysiology, Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rüegg
authors.affiliation: National Poisons Centre, Tox Info Suisse, Associated Institute of the University of Zurich, Zurich, Switzerland.
authors.forename: Hugo
authors.initials: H
authors.lastname: Kupferschmidt
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kraehenbuehl
authors.affiliation: Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Jick
authors.affiliation: Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, Basel Pharmacoepidemiology Unit, University of Basel, Basel, Switzerland. christoph.meier@usb.ch.|Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA. christoph.meier@usb.ch.|Hospital Pharmacy, University Hospital Basel, Spitalstrasse 26, 4031, Basel, Switzerland. christoph.meier@usb.ch.
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Meier
authors.affiliation: Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, Basel Pharmacoepidemiology Unit, University of Basel, Basel, Switzerland.|Medical Department, Zuger Kantonsspital, Zug, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Bodmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016022:Case-Control Studies; D062313:Databases, Pharmaceutical; D003866:Depressive Disorder / Q000188:drug therapy / Q000453:epidemiology*; D057286:Electronic Health Records; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012640:Seizures / Q000139:chemically induced / Q000453:epidemiology*; D013557:Switzerland / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents