Psychiatric Effects of Antiepileptic Drug Therapy
Summary
Antiepileptic drugs (AEDs) are indispensable in controlling seizures, yet their impact on mental health demands close attention. A spectrum of psychiatric effects has been documented, ranging from mood disturbances such as depression, anxiety and irritability to behavioural changes including aggression, agitation and impulsivity. These phenomena may arise during treatment initiation, dose adjustments or even after prolonged therapy. Underlying mechanisms implicate multiple neurotransmitter systems—gamma-aminobutyric acid (GABA), glutamate via AMPA receptors, serotonin and dopamine—alongside alterations in limbic circuitry involving the hippocampus, amygdala and prefrontal cortex. Individual susceptibility is heightened by pre-existing psychiatric comorbidities, genetic variants affecting neurotransmitter metabolism and hormone fluctuations. Clinicians are encouraged to conduct systematic psychiatric assessments before and during AED therapy, tailoring drug selection and dosing to minimise risk. Practical strategies include vigilant monitoring for emergent symptoms, dose titration according to guidelines and collaboration between neurologists, psychiatrists and pharmacists to optimise both seizure control and mental well-being.
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Technical terms
Interictal: Period between epileptic seizures during which behavioural changes may emerge.
Comorbidity: Coexistence of two or more disorders or conditions in the same individual.
Adverse drug reaction (ADR): Harmful or unintended response to a medication administered at normal doses.
AMPA receptor: Ionotropic glutamate receptor subtype that mediates fast excitatory neurotransmission.
Pharmacogenetics: Study of how genetic variation influences individual responses to drugs.
References
- The relationship between psychiatric symptoms and the use of levetiracetam in people with epilepsy. The International Journal of Psychiatry in Medicine (2023).
- Effect of long-term administration of clonazepam, carbamazepine, and valproate on cognitive, psychological, and personality changes in adult epilepsy: a case–control study. Middle East Current Psychiatry (2021).
- Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel. Behavioural Neurology (2018).
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