title: Clobazam and Aggression-Related Adverse Events in Pediatric Patients With Lennox-Gastaut Syndrome.
abstract: BACKGROUND
  Lennox-Gastaut syndrome is an intractable epileptic encephalopathy marked by frequent drop seizures. Most patients develop moderate intellectual disability and behavioral problems, including hyperactivity, aggressiveness, insecurity, and autistic features. Treatment with benzodiazepines, including clobazam, may increase aggression/behavioral problems in patients with Lennox-Gastaut syndrome. Post hoc analyses of data from the OV-1012 trial assessed the potential for behavioral effects with clobazam treatment in pediatric (2 to 18 years) patients with Lennox-Gastaut syndrome.
  
  
  METHODS
  OV-1012 was a phase 3, randomized, double-blind, parallel-group trial comprising a 4-week baseline period, 3-week titration period, and a 12-week maintenance period. Data from 194 patients were analyzed for a history of aggression/behavioral problems, occurrence of aggression-related adverse events, and by assessment of potential drug-related effects on four behavior domains of the Child Behavior Checklist.
  
  
  RESULTS
  Twenty-nine aggression-related adverse events were reported for 27 (13.9%) patients. Similar percentages of clobazam-treated patients with and without a history of aggressive behavior experienced an aggression-related adverse event (16.7% versus 15.5%, respectively). In the medium- and high-dosage clobazam groups, onset of aggression-related adverse effects occurred within the 3-week titration period with 63.2% resolving by the end of the study. Aggression-related adverse event onset and resolution were similar for the low-dosage clobazam and placebo groups. Analysis of baseline to postbaseline T scores for the behavior domains of the Child Behavior Checklist indicated no significant differences between clobazam and placebo.
  
  
  CONCLUSIONS
  Post hoc analyses indicate that the overall rate of aggression with clobazam treatment was low and dosage dependent. Clobazam treatment was effective in reducing drop seizures regardless of aggression experience.
authors.affiliation: Weill Cornell Medical College, New York, New York. Electronic address: jpaolicchimd@gmail.com.
authors.forename: Juliann M
authors.initials: JM
authors.lastname: Paolicchi
authors.affiliation: Weill Cornell Medical College, New York, New York.
authors.forename: Gail
authors.initials: G
authors.lastname: Ross
authors.affiliation: Lundbeck LLC, Deerfield, Illinois.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lee
authors.affiliation: Lundbeck LLC, Deerfield, Illinois.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Drummond
authors.affiliation: Lundbeck LLC, Deerfield, Illinois.
authors.forename: Jouko
authors.initials: J
authors.lastname: Isojarvi
mesh_terms: D000293:Adolescent; D000374:Aggression / Q000187:drug effects*; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D000078306:Clobazam; D004311:Double-Blind Method; D006801:Humans; D065768:Lennox Gastaut Syndrome / Q000188:drug therapy* / Q000523:psychology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D001569:Benzodiazepines; D000078306:Clobazam
keywords: Lennox–Gastaut syndrome; aggression; clobazam; drop seizures; irritability