Trazodone in Dravet Syndrome - European Medical Journal

Trazodone in Dravet Syndrome

2 Mins
*Linda Azevedo Kauppila,1 Isabel Amorim,1 Carla Bentes,2 Ana Rita Peralta2

The authors have declared no conflicts of interest.

EMJ Neurol. ;6[1]:62-63. Abstract Review No. AR11.
Dravet syndrome (DS), serotonin pathways, trazodone

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

Dravet syndrome (DS) is an epileptic encephalopathy most commonly associated with SCN1A mutations and is typically refractory to antiepileptic drugs (AED). DS normally presents in the first year of life,1-3 and different types of seizures may occur.2,3 Along with epilepsy, DS is associated with developmental delay and an elevated risk of sudden death.2

Here we report the case of a 25-year-old woman with DS-related epilepsy (SCN1A mutation) with daily seizures since the age of 5 months, associated with developmental delay. Many AED combinations were tried with no apparent benefit. Seizure-free periods or a significant reduction in seizure frequency were not noted during the course of the disease. Over the years, the patient maintained daily seizures, predominantly during the night, averaging two tonic-clonic seizures a night and an uncountable number of myoclonic seizures, documented both clinically and neurophysiologically. Trazodone was started due to complaints of insomnia. Clinically, the patient’s mother noted a significant improvement regarding seizure frequency, with <1 tonic-clonic seizure per month. Electroencephalogram and polysomnographic studies were repeated following 4 months of treatment with trazodone. The studies showed considerable improvement of interictal epileptiform activity and myoclonic seizures, with only subtle changes in sleep structure. This benefit persisted after 1 year of follow-up.

Recent animal studies have suggested that serotonergic pathway modulation is a potential therapeutic target for DS.4 Clinically, there are very few cases of such evidence with the use of drugs such as lorcaserin or fenfluramine.4-6 To the best of our knowledge, no clinical data showing that trazodone may be a useful AED in DS patients are available and our case provides this novel clinical evidence.

Despite the limitation of this report being an isolated case with possible chance factors, our data, given the outstanding and 12-month improvement, suggest a direct antiepileptic role (as opposed to indirect improvement in sleep structure) of trazodone in DS, reinforcing the beneficial effect of serotonergic modulation in these patients; however, the need for additional investigation on this subject is clear. One must not forget that patients with DS rarely achieve seizure freedom and have a high probability of recurrent seizures, including status epilepticus.7 Additionally, sudden unexplained death is also a risk that must be considered in these patients.7 In the management of these patients, one tries to reduce seizure frequency but also to limit the adverse reactions.7 Trazodone does not usually present with significant adverse effects and has a beneficial pharmacological profile.8 If trazodone were to be found to represent an efficacious drug for these patients, it could significantly change the treatment paradigm of DS.

We hope that the presentation of this case at the EAN Congress may help disseminate this innovative concept and promote the use of serotonergic agents in DS patients, possibly to compile clinical data regarding the use of trazodone in these patients.

Millichap JJ et al. Child Neurology: Dravet syndrome: When to suspect the diagnosis. Neurology. 2009;73(13):e59-62. Aras LM et al. The European patient with Dravet syndrome: Results from a parent-reported survey on antiepileptic drug use in the European population with Dravet syndrome. Epilepsy Behav. 2015;44:104-9. Wu YW et al. Incidence of Dravet syndrome in a US population. Pediatrics. 2015;136(5):e1310-5. Griffin A et al. Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain. 2017;140(3):669-83. Aicardi J, Gastaut H. Treatment of self-induced photosensitive epilepsy with fenfluramine. N Engl J Med. 1985;313(22):1419. Ceulemans B et al. Successful use of fenfluramine as an add-on treatment for Dravet syndrome. Epilepsia. 2012;53(7):1131-9. Wirrell EC. Treatment of Dravet syndrome. Can J Neurol Sci. 2016;43(Suppl 3):S13-8. Morin AK et al. Therapeutic options for sleep-maintenance and sleep-onset insomnia. Pharmacotherapy. 2007;27(1):89-110.

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