Comparative Efficacy and Safety of Antiepileptic Drugs (AEDs) in the Management of Focal and Generalized Seizures

Epilepsy is a prevalent neurological disorder affecting individuals across all age groups. It is characterized by recurrent, unprovoked seizures that can have a profound impact on quality of life, functional independence, and psychosocial well-being. Effective management of epilepsy relies heavily on antiepileptic drugs (AEDs), which aim to control seizures and prevent recurrence with minimal adverse effects. This systematic review aims to compare the efficacy and safety profiles of commonly used AEDs in the treatment of both focal and generalized seizures. The focus is on identifying optimal pharmacological options for various patient subgroups, including pediatric, adult, and elderly populations, with considerations for monotherapy versus combination therapy. A comprehensive search was conducted using PubMed, Scopus, and the Cochrane Library for studies published up to March 2025. Eligible studies included randomized controlled trials (RCTs), cohort studies, and meta-analyses evaluating the use of AEDs for focal or generalized epilepsy. Key outcome measures included seizure freedom rates, adverse events, drug discontinuation due to intolerance, and quality-of-life impacts. Of 5,438 studies initially identified, 96 met the inclusion criteria and were systematically analyzed. For focal seizures, lamotrigine and levetiracetam demonstrated high efficacy with favorable safety profiles, while carbamazepine, though highly effective, showed increased rates of adverse effects. In generalized seizures, valproate remained the most effective but posed significant teratogenic risks. Levetiracetam emerged as a safer alternative, especially for women of childbearing potential. Combination therapy improved seizure control in drug-resistant cases but increased the risk of cumulative side effects. Levetiracetam and lamotrigine are effective and well-tolerated across seizure types, making them strong candidates for first-line therapy. Valproate remains highly efficacious in generalized seizures but requires careful consideration due to safety concerns. This review supports individualized treatment plans based on patient characteristics and encourages further comparative research, particularly involving newer AEDs and real-world effectiveness.