Adjunctive Therapy Strategies for Focal Epilepsy Management

Focal epilepsy, characterised by seizures originating in a discrete region of the brain, often proves resistant to monotherapy with a single antiseizure medication. Adjunctive therapy—adding a second or subsequent intervention to an existing regimen—aims to achieve better seizure control, improve quality of life and minimise adverse effects. Recent advances have centred on novel pharmacological agents with distinct mechanisms of action, as well as non-pharmacological approaches such as neuromodulation and dietary modifications. By targeting complementary pathways, these strategies can yield synergistic effects, reduce seizure frequency and increase the proportion of patients achieving sustained seizure freedom.

Pharmacological adjunctive options include third-generation synaptic vesicle protein 2A ligands, selective sodium-channel blockers, and modulators of neurotransmitter systems. Beyond medication, neurostimulation techniques—such as vagus nerve stimulation and responsive neurostimulation—provide targeted electrical modulation of epileptogenic zones. Dietary approaches, notably the ketogenic and modified Atkins diets, may further augment seizure control in appropriately selected individuals. A personalised treatment plan, informed by a patient’s seizure semiology, comorbidities and pharmacokinetic profile, remains central to optimising outcomes in focal epilepsy.

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Adjunctive Therapy Strategies for Focal Epilepsy Management publication trend

The graph below shows the total number of articles in adjunctive therapy strategies for focal epilepsy management across all publications each year (not limited to Nature Index journals).

Technical terms

Focal epilepsy: A form of epilepsy in which seizures originate in a specific area of the brain rather than affecting both hemispheres simultaneously.

Adjunctive therapy: The addition of a supplementary treatment to a primary intervention to enhance therapeutic efficacy.

Seizure freedom: The complete absence of seizures over a defined period, often used as a primary treatment goal.

Responder rate: The proportion of patients experiencing a clinically meaningful reduction (commonly ≥ 50 %) in seizure frequency.

Synaptic vesicle glycoprotein 2A (SV2A): A protein involved in neurotransmitter release, targeted by certain third-generation antiseizure medications to reduce neuronal hyperexcitability.

Voltage-gated sodium channels: Transmembrane proteins that initiate and propagate action potentials; modulation of these channels can stabilise neuronal membranes and prevent seizure propagation.

References

1. Effectiveness and tolerability of brivaracetam in patients with epilepsy stratified by comorbidities and etiology in the real world: 12-month subgroup data from the international EXPERIENCE pooled analysis. Journal of Neurology (2024).
2. Euro-Esli: a European audit of real-world use of eslicarbazepine acetate as a treatment for partial-onset seizures. Journal of Neurology (2017).
3. Retention, efficacy, tolerability, and quality of life during long-term adjunctive brivaracetam treatment by number of lifetime antiseizure medications: A post hoc analysis of phase 3 trials in adults with focal seizures. Epilepsy & Behavior (2022).