A Systematic Review of Antiepileptic Drug Initiation and Withdrawal

Background: The proper clinical context to initiate or discontinue antiepileptic drug (AED) treatment has been extensively studied over the past 40 years. Differences in study design and methodology have led to reports of seizure recurrence rates of 7% to 96% in drug initiation trials and seizure relapse rates of 12% to 67% in drug withdrawal trials. A number of different historical and clinical factors have been cited in various studies as altering seizure risk. Our objective was to review the data from large, well-conducted, prospective studies. Review Summary: We performed an electronic search of 3 medical and scientific databases for articles on initiating or withdrawing antiepileptic medication. Our review focused primarily on articles meeting specific inclusion and exclusion criteria. We discuss the risk of seizure recurrence after a first seizure and the factors associated with an elevated risk of recurrence. The risks of treatment, including life-threatening idiosyncratic reactions and dose-related physical and cognitive side effects are reviewed. We also summarize the data on the seizure relapse risk after drug discontinuation and the factors associated with an increased relapse risk. Benefits of successful AED withdrawal are highlighted. The special considerations of treatment initiation and withdrawal in the pediatric population are explored. We propose general guidelines to assist the clinician in evaluating the risk/benefit ratio of initiating and withdrawing antiepileptic drugs. Conclusion: Drug initiation after a first seizure decreases early seizure recurrence, but does not affect the long-term prognosis of developing epilepsy. Medication withdrawal after a period of seizure remission increases the risk of relapse, but the benefits of successful AED discontinuation may be substantial. In the end, the decision of whether to initiate treatment after a single seizure and whether to withdraw AED therapy in patients enjoying a prolonged period of seizure freedom should be made on an individual case basis, which balances the risk of seizure relapse and subsequent disability against the likely impact of medication-related physical, cognitive, and psychologic adverse effects.