The impact of side effects on long-term retention in three new antiepileptic drugs

Seizure. 2009 Jun;18(5):327-31. doi: 10.1016/j.seizure.2008.11.006. Epub 2008 Dec 24.

Abstract

Objective: To determine long-term retention, percentage of patients withdrawing because of adverse events, percentage of patients achieving seizure freedom, safety profile of the new anti-epileptic drugs lamotrigine, levetiracetam and topiramate.

Methods: All patients treated with lamotrigine, levetiracetam or topiramate in the Epilepsy Centre were identified. Each drug was analyzed from introduction of the drug in the Netherlands up to a final assessment point 2 years later.

Results: Data from 1066 patients were included: 336 for lamotrigine, 301 for levetiracetam, 429 for topiramate. Two-year retention rates were 69.2% (lamotrigine), 45.8% (levetiracetam), 38.3% (topiramate); (LTG vs. LEV at p<0.001; LTG vs. TPM at p<0.001; LEV vs. TPM at p=0.005). Seizure freedom rates were lowest for lamotrigine and highest for levetiracetam. Adverse events played a role in drug discontinuation in 154/429 patients (35.9%) on topiramate, 52/336 patients (15.5%) on lamotrigine (p<0.001), 68/301 patients (22.5%) on levetiracetam (p<0.001). Mood and general CNS-effects are common in patients on lamotrigine and levetiracetam, and neurocognitive side effects are most prevalent in patients on topiramate. A positive effect on cognition is frequently noted in patients on lamotrigine.

Conclusion: A drug that is only modestly efficacious but has a favourable safety profile may look better than a drug that is more efficacious but produces clinically meaningful adverse events. Therefore, a drug's retention rate is mainly determined by its side effect profile. As a consequence, retention rate was highest for lamotrigine and lowest for topiramate. Intermediate retention rates were seen with levetiracetam use.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use*
  • Drug Utilization / statistics & numerical data
  • Epilepsy / drug therapy*
  • Fructose / analogs & derivatives
  • Humans
  • Lamotrigine
  • Levetiracetam
  • Longitudinal Studies
  • Patient Compliance / psychology*
  • Piracetam / analogs & derivatives
  • Time Factors
  • Topiramate
  • Treatment Outcome
  • Triazines

Substances

  • Anticonvulsants
  • Triazines
  • Topiramate
  • Fructose
  • Levetiracetam
  • Lamotrigine
  • Piracetam