Systematic Literature Review of Adjunctive Anti-Epileptic Drug Trials In Patients With Primary Generalized Tonic-Clonic Seizures Illustrates Changes in Standard of Care Over 12-20 Years.

• Four anti-epileptic drugs (AEDs) have been approved for the adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS) in adults: topiramate [TPM], lamotrigine [LTG]/ lamotrigine-XR [LTG-XR], levetiracetam [LEV], and perampanel [PER]. • Five randomized-controlled trials were conducted to support these approvals [1-5]. Lamotrigine-XR applies to the US but not the EU. • These trials enrolled patients over a 12-20 year timeframe and would be capable of illustrating changes in practices patterns and trial designs over time: • TPM-RCT [6]: March 1994 – December 1999 • LTG-RCT [7]: December 2000 – November 2003 • LEV-RCT [8]: September 2001 – June 2005 • LTG-XR-RCT [9]: December 2004 – July 2008 • PER-RCT [10]: September 2011 – May 2014 Figure 3. Trial Sample Sizes (1-5)