Abstract Details

Title Aggression in Lennox-Gastaut Syndrome (LGS) Patients Treated with Clobazam during the CONTAIN Trial

Topic Epilepsy

Presentation(s) P04 - (-)

Poster/Presentation
Number 204

Objective

Background BACKGROUND: Aggression and irritability occur frequently in LGS patients. Benzodiazepines are often used for seizures in LGS, but have been associated with aggression. This can lead to discontinuation of effective therapies.

Design/Methods DESIGN/METHODS: LGS patients 2-60 years of age enrolled. Following a 4-week baseline, patients who had ?2 drop seizures/week were randomized to placebo or 1 of 3 dosages of clobazam (0.25, 0.5, and 1.0 mg/kg/day), ?40 mg/day maximum. Treatment included a 3-week titration phase, followed by a 12-week maintenance phase. The safety population included all who received ?1 dose of study drug or placebo. We searched the AE database for the preferred terms of aggression, irritability, abnormal behavior, perseveration, and negativism, using MedDRA terms as a guide (identified as aggression-related events).

Results RESULTS: 301 patients were screened, 238 were randomized, 217 comprised the modified, intention-to-treat population (efficacy analyses), and 177 completed the study. Four patients discontinued because of aggression (1 medium- and 3 high-dosage patients). 37/238 (15.5%) experienced 43 aggression-related events, occurrence of which was dosage-related. Time to onset for the majority of events in the medium- and high-dosage groups was during the 3-week titration, while in the placebo- and low-dosage groups, time to onset was distributed throughout the 15-week study. Resolution occurred for 43%, 40%, 63%, and 73% of events in the placebo, and low-, medium-, and high-dosage groups respectively. >50% of events resolved within 40 days, and all patients who received high-dosage clobazam who resolved did so within [sim]60 days.

Conclusions CONCLUSIONS: Onset of aggression-related events was dosage-related, onset of majority of events was during titration, and the majority resolved, contrary to standard belief about aggression outcomes, especially in the medium- and high-dosage groups.

Authors/Disclosures
Juliann M. Paolicchi, MD PRESENTER	No disclosure on file
Jouko I. Isojarvi, MD, PhD (Lundbeck)	No disclosure on file
Deborah A. Lee, MD, PhD (AlaWai Neurology Consulting LLC)	No disclosure on file
	No disclosure on file
	No disclosure on file

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