Background: Controversy exists about the safety of substituting generic anti-epileptic drugs (AEDs). Lamotrigine, the prototypical newer AED, is often used for psychiatric and neurological conditions other than epilepsy. The safety of generic substitution of lamotrigine in diverse populations of AED users is unclear.
Objective: The objective of this study was to evaluate potential associations between generic substitution of lamotrigine and adverse consequences in a population of diverse users of this drug.
Study Design: This study was a retrospective cohort-crossover design using state Medicaid claims data from July 2006 through June 2009.
Methods: Subjects were included in the cohort if they converted from brand to generic lamotrigine and had 2 years of lamotrigine use prior to conversion. The frequency of emergency department (ED) visits, hospitalizations and condition-specific ED visits or hospitalizations were recorded in the 60 days immediately following the conversion to generic lamotrigine, then compared with the incidence of the same events during a randomly selected time period indexed to one of the patient’s past refills of branded lamotrigine. Multi-variate conditional logistic regression was used to quantify the association between generic conversion and health services utilization while controlling for changes in lamotrigine dose and concurrent drug use.
Results: Of the 616 unique subjects included in this analysis, epilepsy was the most common diagnosis (41%), followed by bipolar disorder (32%), pain (30%) and migraine (18%). Conversion to generic lamotrigine was not associated with a statistically significant increase in the odds of an ED visit (adjusted odds ratio [AOR]=1.35; 95% confidence interval [CI] 0.92, 1.97), hospitalization (AOR=1.21; 95% CI 0.60, 2.50) or condition-specific encounter (AOR 1.75; 95 CI 0.87, 3.51).
Conclusions: A statistically significant increase in ED visits, hospitalizations or condition-specific encounters was not observed following the switch from brand to generic lamotrigine, although a type II error cannot be ruled out.
Migraine Lamotrigine Topiramate Emergency Department Visit Generic Conversion
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This study was unfunded. The authors do not have any conflicts of interest to disclose.
Haas JS, Phillips KA, Gerstenberger EP, et al. Potential savings from substituting generic drugs for brand-name drugs: Medical Expenditure Panel Survey, 1997–2000. Ann Intern Med 2005; 142: 891–7PubMedCrossRefGoogle Scholar
Shrank WH, Choudhry NK, Liberman JN, et al. The use of generic drugs in prevention of chronic disease is far more cost-effective than thought, and may save money. Health Aff (Millwood) 2011; 30: 1351–7CrossRefGoogle Scholar
Meredith P. Bioequivalence and other unresolved issues in generic drug substitution. Clin Ther 2003; 25: 2875–90PubMedCrossRefGoogle Scholar
Davit BM, Nwakama PE, Buehler GJ, et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann Pharmacother 2009; 43: 1583–97PubMedCrossRefGoogle Scholar
Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease. JAMA 2008; 300: 2514–26PubMedCrossRefGoogle Scholar
Krauss GL, Caffo B, Chang Y-T, et al. Assessing bioequi-valence of generic antiepilepsy drugs. Ann Neurol 2011; 70: 221–8PubMedCrossRefGoogle Scholar
Liow K, Barkley GL, Pollard JR, et al. Position statement on the coverage of anticonvulsant drugs for the treatment of epilepsy. Neurology 2007; 68: 1249–50PubMedCrossRefGoogle Scholar
Kesselheim AS, Stedman MR, Bubrick EJ, et al. Seizure outcomes following the use of generic versus brand-name antiepileptic drugs: a systematic review and meta-analysis. Drugs 2010; 70: 605–21PubMedCrossRefGoogle Scholar
Yamada M, Welty TE. Generic substitution of antiepileptic drugs: a systematic review of prospective and retrospective studies. Ann Pharmacother 2011; 45: 1406–15PubMedCrossRefGoogle Scholar
Desmarais JE, Beauclair L, Margolese HC. Switching from brand-name to generic psychotropic medications: a literature review. CNS Neurosci Ther 2011; 17: 750–60PubMedCrossRefGoogle Scholar
Makus KG, McCormick J. Identification of adverse reactions that can occur on substitution of generic for branded lamo-trigine in patients with epilepsy. Clin Ther 2007; 29: 334–41PubMedCrossRefGoogle Scholar
Savica R, Beghi E, Mazzaglia G, et al. Prescribing patterns of antiepileptic drugs in Italy: a nationwide population-based study in the years 2000–2005. Eur J Neurol 2007; 14: 1317–21PubMedCrossRefGoogle Scholar
Chen H, Deshpande AD, Jiang R, et al. An epidemiological investigation of off-label anticonvulsant drug use in the Georgia Medicaid population. Pharmacoepidemiol Drug Saf 2005; 14:629–38PubMedCrossRefGoogle Scholar
Chen H, Reeves JH, Fincham JE, et al. Off-label use of antidepressant, anticonvulsant, and antipsychotic medications among Georgia Medicaid enrollees in 2001. J Clin Psychiatry 2006; 67: 972–82PubMedCrossRefGoogle Scholar
Maclure M. The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol 1991; 133: 144–53PubMedGoogle Scholar
Maclure M, Mittleman MA. Should we use a case-crossover design? Ann Rev Public Health 2000; 21: 193–221CrossRefGoogle Scholar
Goldsmith DR, Wagstaff AJ, Ibbotson T, et al. Spotlight on lamotrigine in bipolar disorder. CNS Drugs 2004; 18: 63–7PubMedCrossRefGoogle Scholar
Rascati KL, Richards KM, Johnsrud MT, et al. Effects of antiepileptic drug substitutions on epileptic events requiring acute care. Pharmacotherapy 2009; 29: 769–74PubMedCrossRefGoogle Scholar
Zachry III WM, Doan QD, Clewell JD, et al. Case-control analysis of ambulance, emergency room, or inpatient hospital events for epilepsy and antiepileptic drug formulation changes. Epilepsia 2009; 50: 493–500PubMedCrossRefGoogle Scholar
Hansen RN, Campbell JD, Sullivan SD. Association between antiepileptic drug switching and epilepsy-related events. Epilepsy Behav 2009; 15: 481–5PubMedCrossRefGoogle Scholar
Devine ST, Weisbart E, Barron J, et al. Acute epilepsy exacerbations in patients switched between A-rated antiepileptic drugs. Curr Med Res Opin 2010; 26: 455–63PubMedCrossRefGoogle Scholar
LeLorier J, Sheng Duh M, Emmanuel Paradis P, et al. Economic impact of generic substitution of lamotrigine: projected costs in the US using findings in a Canadian setting. Curr Med Res Opin 2008; 24: 1069–81PubMedCrossRefGoogle Scholar
LeLorier J, Duh MS, Paradis PE, et al. Clinical con-sequences of generic substitution of lamotrigine for patients with epilepsy. Neurology 2008; 70: 2179–86PubMedCrossRefGoogle Scholar
Duh MS, Paradis PE, Latremouille-Viau D, et al. The risks and costs of multiple-generic substitution of topiramate. Neurology 2009; 72: 2122–9PubMedCrossRefGoogle Scholar
Labiner DM, Paradis PE, Manjunath R, et al. Generic antiepileptic drugs and associated medical resource utilization in the United States. Neurology 2010; 74: 1566–74PubMedCrossRefGoogle Scholar
Erickson SC, Le L, Ramsey SD, et al. Clinical and pharmacy utilization outcomes with brand to generic antiepileptic switches in patients with epilepsy. Epilepsia 2011; 52: 1365–71PubMedCrossRefGoogle Scholar
Gagne JJ, Avorn J, Shrank WH, et al. Refilling and switching of antiepileptic drugs and seizure-related events. Clin Pharmacol Ther 2010; 88: 347–53PubMedCrossRefGoogle Scholar
Schneeweiss S, Avorn J. A review of uses of health care utilization databases for epidemiologic research on therapeutics. J Clinl Epidemiol 2005; 58: 323–37CrossRefGoogle Scholar