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RAUMATIC STRESS IS A SIGNIFIcant public health problem 1 that frequently results in a distinctive pattern of persistent and disabling psychological and physiological symptoms. 2,3 Once thought to be primarily limited to soldiers in combat, posttraumatic stress disorder (PTSD) is now recognized in civilians, including those who have experienced natural disasters, physical and sexual assault, fire, motor vehicle and other serious trauma, as well as those who have witnessed inflicted injury or death. Exposure to a traumatic event is common, estimated in the range of 5% to 35% annually, with a lifetime exposure to 1 or more traumatic events occurring in more than 50% of the US population. 1 The clinical presentation of PTSD is characterized by moderate-to-severe symptoms in 3 separate domains: reexperiencing (intrusive thoughts, nightmares, flashbacks, images, or memories), emotional numbing and avoidance (flattened affect or detachment, loss of interest and motivation, and avoidance of any activity, place, person, or topic associated with the trauma); and Author Affiliations and Financial Disclosures are listed at the end of this article.

for the FAiRE, DS Study Group IMPORTANCE Fenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens. OBJECTIVE To determine whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were taking stiripentol-inclusive regimens. DESIGN, SETTING, AND PARTICIPANTSThis double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted in multiple centers. Eligible patients were children aged 2 to 18 years with a confirmed clinical diagnosis of Dravet syndrome who were receiving stable, stiripentol-inclusive antiepileptic drug regimens. INTERVENTIONSPatients with 6 or more convulsive seizures during the 6-week baseline period were randomly assigned to receive fenfluramine, 0.4 mg/kg/d (maximum, 17 mg/d), or a placebo. After titration (3 weeks), patients' assigned dosages were maintained for 12 additional weeks. Caregivers recorded seizures via a daily electronic diary. MAIN OUTCOMES AND MEASURESThe primary efficacy end point was the change in mean monthly convulsive seizure frequency between fenfluramine and placebo during the combined titration and maintenance periods relative to baseline. RESULTS A total of 115 eligible patients were identified; of these, 87 patients (mean [SD], age 9.1 [4.8] years; 50 male patients [57%]; mean baseline frequency of seizures, approximately 25 convulsive seizures per month) were enrolled and randomized to fenfluramine, 0.4 mg/kg/d (n = 43) or placebo (n = 44). Patients treated with fenfluramine achieved a 54.0% (95% CI, 35.6%-67.2%; P < .001) greater reduction in mean monthly convulsive seizure frequency than those receiving the placebo. With fenfluramine, 54% of patients demonstrated a clinically meaningful (Ն50%) reduction in monthly convulsive seizure frequency vs 5% with placebo (P < .001). The median (range) longest seizure-free interval was 22 (3.0-105.0) days with fenfluramine and 13 (1.0-40.0) days with placebo (P = .004). The most common adverse events were decreased appetite (19 patients taking fenfluramine [44%] vs 5 taking placebo [11%]), fatigue (11 [26%] vs 2 [5%]), diarrhea (10 [23%] vs 3 [7%]), and pyrexia (11 [26%] vs 4 [9%]). Cardiac monitoring demonstrated no clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension.

The results of the current study suggest that sertraline is a safe, well-tolerated, and significantly effective treatment for PTSD.

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