Generic
antiepileptic drugs achieve blood concentrations similar to those of innovator drugs in healthy volunteers, but their comparative effectiveness has not been well evaluated. Thus, we assessed the efficacy, tolerability, and safety of innovator versus generic
antiepileptic drugs. We searched the MEDLINE database, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science for studies that evaluated innovator and generic
antiepileptic drugs in patients with
epilepsy and reported data on prespecified outcomes. We extracted data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes. Compared with initiation of innovator
antiepileptic drugs, initiation of generic
antiepileptic drugs did not significantly alter seizure occurrence (relative risk [RR] 0.87, 95% confidence interval [CI] 0.64-1.18; strength of evidence: low) or frequency (standardized mean difference 0.03, 95% CI -0.08-0.14; strength of evidence: low), withdrawals due to lack of efficacy (RR 1.02, 95% CI 0.41-2.54; strength of evidence: low) or adverse events (RR 0.79, 95% CI 0.28-2.20; strength of evidence: low), pharmacokinetic concentrations (maximum, minimum, or area under the curve [strength of evidence: low]), or a myriad of adverse events (strength of evidence: low or insufficient) in clinical trials. In qualitatively evaluated observational studies, switching between forms of
antiepileptic drug (innovator to generic, generic to generic) may increase the risk of hospitalization (strength of evidence: low),
hospital stay duration (strength of evidence: low), and a composite end point of medical service utilization (strength of evidence: insufficient) but may not increase
outpatient service utilization (strength of evidence: low). Data are limited predominantly to
carbamazepine,
phenytoin, and
valproic acid. Clinical trials are limited by small sample size, short-term nature, and lack of specification of A-rated generic products (generics that the United States Food and Drug Administration has deemed bioequivalent to the innovator
drug). Observational trials lack full accounting for confounders and have inherent limitations. With a low strength of evidence, it appears that initiating an innovator or generic
antiepileptic drug will provide similar efficacy, tolerability, and safety but that switching from one form to the other may be associated with more hospitalizations and longer
hospital stays.