Antiepileptic Drugs in Non-Epilepsy Disorders: Relations between Mechanisms of Action and Clinical Efficacy
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.
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Benzodiazepine use in autism is relatively uncommon due to concerns of behavioral disinhibition; some anticonvulsants likely exert GABAergic effects and are used for mood stabilization; there is ongoing interest in GABAergic treatments for catatonia in autism.
“While benzodiazepine use in autism is relatively uncommon, owing to concerns of behavioral disinhibition, some anticonvulsants that likely exert GABAergic effects are used for mood stabilization [262], and there is ongoing interest in the potential role of GABAergic treatments for catatonia in autism [263].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [262]
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- Authors
- Johannessen Landmark, C.
- Venue
- CNS Drugs
- Published
- 2008
- Volume
- 22
- Issue
- 1
- Pages
- 27-47
- ISSN
- 1172-7047 (ISSN-L)
- OpenAlex
- W2195324906
- Cited by
- 316
- References
- 157
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 11 · 2023: 15 · 2022: 9 · 2021: 7 · 2020: 5 · 2019: 17 · 2018: 10 · 2017: 10 · 2016: 22 · 2015: 15 · 2014: 18 · 2013: 27 · 2012: 28
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- antiepileptic drugs, off-label drug use, essential tremor, neuropathic pain, migraine, anxiety disorders, schizophrenia, bipolar disorder, GABAergic neurotransmission, glutamatergic neurotransmission, ion channels, valproic acid, carbamazepine, lamotrigine, topiramate, gabapentin, pregabalin, tiagabine, mood disorders, neuroprotection, second-generation antiepileptic drugs, drug selection
- MeSH terms
- Anticonvulsants, Anxiety, Mental Disorders, Bipolar Disorder, Humans, Migraine Disorders, Nervous System Diseases, Pain, Schizophrenia, Essential Tremor
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