Nonepileptic Uses of Antiepileptic Drugs in Children and Adolescents
Department of Neurology and the Comprehensive Epilepsy Management Center, Bronx, New York, USA.Pediatric Neurology (Impact Factor: 1.7). 07/2006; 34(6):421-32. DOI: 10.1016/j.pediatrneurol.2005.08.017
Antiepileptic drugs are often prescribed for nonepileptic neurologic and psychiatric conditions. The United States Food and Drug Administration has approved several antiepileptic drugs for the treatment of neuropathic pain, migraine, and mania in adults. For pediatric patients, use of antiepileptic drugs for non-seizure-related purposes is supported mainly by adult studies, open-label trials, and case reports. Summarized here is the published literature for or against the use of antiepileptic drugs for neuropathic pain, migraine, movement disorders, bipolar disorder, aggressive behavior, and pervasive developmental disorders in children and adolescents. Using the American Academy of Neurology's four-tiered classification scheme for a therapeutic article and translation to a recommendation rating, there are no nonepileptic disorders for which antiepileptic drugs have been established as effective for pediatric patients. Valproate and carbamazepine are "possibly effective" in the treatment of Sydenham chorea, and valproate is "probably effective" in decreasing aggressive behavior. Carbamazepine is "probably ineffective" in the treatment of aggression, and lamotrigine is "possibly ineffective" in improving the core symptom of pervasive developmental disorders. Despite the frequent use of antiepileptic drugs in the treatment of juvenile bipolar disorder, migraine, and neuropathic pain, the data are insufficient to make recommendations regarding the efficacy of antiepileptics in these conditions in children and adolescents.
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ABSTRACT: Antiepileptic drugs (AEDs) are used extensively to treat multiple non-epilepsy disorders, both in neurology and psychiatry. This article provides a review of the clinical efficacy of AEDs in non-epilepsy disorders based on recently published preclinical and clinical studies, and attempts to relate this efficacy to the mechanism of action of AEDs and pathophysiological processes associated with the disorders. Some newer indications for AEDs have been established, while others are under investigation. The disorders where AEDs have been demonstrated to be of clinical importance include neurological disorders, such as essential tremor, neuropathic pain and migraine, and psychiatric disorders, including anxiety, schizophrenia and bipolar disorder. Many of the AEDs have various targets of action in the synapse and have several proposed relevant mechanisms of action in epilepsy and in other disorders. Pathophysiological processes disturb neuronal excitability by modulating ion channels, receptors and intracellular signalling pathways, and these are targets for the pharmacological action of various AEDs. Attention is focused on the glutamatergic and GABAergic synapses. In psychiatric conditions such as schizophrenia and bipolar disorder, AEDs such as valproate, carbamazepine and lamotrigine appear to have clear roles based on their effect on intracellular pathways. On the other hand, some AEDs, e.g. topiramate, have efficacy for nonpsychiatric disorders including migraine, possibly by enhancing GABAergic and reducing glutamatergic neurotransmission. AEDs that seem to enhance GABAergic neurotransmission, e.g. tiagabine, valproate, gabapentin and possibly levetiracetam, may have a role in treating neurological disorders such as essential tremor, or anxiety disorders. AEDs with effects on voltage-gated sodium or calcium channels may be advantageous in treating neuropathic pain, e.g. gabapentin, pregabalin, carbamazepine, oxcarbazepine, lamotrigine and valproate. Co-morbid conditions associated with epilepsy, such as mood disorders and migraine, may often respond to treatment with AEDs. Other possible disorders where AEDs may be of clinical importance include cancer, HIV infection, drug and alcohol abuse, and also in neuroprotection. A future challenge is to evaluate the second-generation AEDs in non-epilepsy disorders and to design clinical trials to study their effects in such disorders in paediatric patients. Differentiation between the main mechanisms of action of the AEDs needs more consideration in drug selection for tailored treatment of the various non-epilepsy disorders.CNS Drugs 02/2008; 22(1):27-47. · 5.11 Impact Factor
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