Drug-resistant epilepsy treatment: what to do when two suitable medication schedules have not controlled seizures

Continuing seizures do not mean that care must consist only of adding more medicines. Once drug resistance is established, a comprehensive epilepsy service can review the diagnosis, seizure classification, and treatment history while considering surgery, neurostimulation, and other relevant approaches. Drug resistant describes the response to treatment so far. It does not establish that further improvement is impossible. ILAE: Drug-Resistant Epilepsy, definition and clinical resourcesJehi et al.: Timing of referral for epilepsy surgery evaluation, ILAE consensus, 2022

Key takeaways

These excerpts come from the original article. Read the full sections below for context.

The ILAE definition requires adequate trials of two tolerated, appropriately selected and correctly used antiseizure medication schedules without sustained seizure freedom. These can be single-drug or combination schedules. A brief exposure, an inadequate trial, or a medicine unsuitable for the actual seizure type cannot simply be counted as an equivalent treatment failure. NICE NG217: Terms used, drug-resistant epilepsy definition, updated January 2025
Selected focal epilepsy may be treated by removal or ablation of particular tissue, while some complex conditions involve a disconnection strategy to limit seizure spread. Suitability depends on the distribution of disease, the seizure network, and functional risk. A smaller incision does not independently establish a better clinical choice or guarantee preservation of memory and language. NINDS: Epilepsy and Seizures
Ask the clinician to separate what continues now, what information is still needed, and which choices depend on forthcoming results. If an operation is not currently recommended, clarify whether localization is incomplete, functional risk is unacceptable, or another approach is more suitable. These reasons determine what could usefully be reconsidered later.

Quick answer

Continuing seizures do not mean that care must consist only of adding more medicines. Once drug resistance is established, a comprehensive epilepsy service can review the diagnosis, seizure classification, and treatment history while considering surgery, neurostimulation, and other relevant approaches. Drug resistant describes the response to treatment so far. It does not establish that further improvement is impossible. ILAE: Drug-Resistant Epilepsy, definition and clinical resources Jehi et al.: Timing of referral for epilepsy surgery evaluation, ILAE consensus, 2022

Full guide

Continuing seizures do not mean that care must consist only of adding more medicines. Once drug resistance is established, a comprehensive epilepsy service can review the diagnosis, seizure classification, and treatment history while considering surgery, neurostimulation, and other relevant approaches. Drug resistant describes the response to treatment so far. It does not establish that further improvement is impossible. ILAE: Drug-Resistant Epilepsy, definition and clinical resources Jehi et al.: Timing of referral for epilepsy surgery evaluation, ILAE consensus, 2022

Establish what the two unsuccessful treatment schedules involved

The ILAE definition requires adequate trials of two tolerated, appropriately selected and correctly used antiseizure medication schedules without sustained seizure freedom. These can be single-drug or combination schedules. A brief exposure, an inadequate trial, or a medicine unsuitable for the actual seizure type cannot simply be counted as an equivalent treatment failure. NICE NG217: Terms used, drug-resistant epilepsy definition, updated January 2025

Prepare the name, actual use, duration, missed doses, observed effect on each event type, and reason for stopping each medicine. An adverse reaction that prevented continued treatment is clinically important, but it differs from persistent seizures despite an adequate tolerated trial. Reviewing this history is a way to find actionable problems, not a judgment about the patient's effort or reliability.

Reconsider the nature of events that have continued

Syncope, sleep-related events, and functional seizures can resemble epilepsy, and more than one kind of event can coexist in the same person. The assessment needs a description of what happens before, during, and after an episode. When indicated, video-EEG monitoring helps relate the observed event to electrical findings. NICE NG217: Diagnosis and assessment of epilepsy

A normal routine EEG does not exclude epilepsy, and an abnormal tracing is not a substitute for the full clinical assessment. A representative home video can be helpful when it can be obtained safely. Recording must not delay first aid, and patients should never stop medicines at home to provoke a more convincing event for the camera.

Describe recovery as carefully as the dramatic part of the episode. Confusion, weakness, memory, and the time needed to return to usual activity may help the clinician understand the event. If the patient has several patterns, give each a separate description rather than assuming that all belong to one category.

Classification changes which treatment makes sense

The 2025 ILAE seizure classification retains four main classes: focal, generalized, unknown whether focal or generalized, and unclassified. It also emphasizes describing the chronological sequence of manifestations. Older records may use earlier terminology; a specialist can interpret that language without treating a wording change alone as evidence that the earlier diagnosis was wrong. ILAE: Updated classification of epileptic seizures, 2025

Seizure type, epilepsy type, syndrome, and cause are related but distinct levels of description. Similar bilateral convulsions can arise in different disorders. A medicine useful for one syndrome may be inappropriate for another, so another person's response cannot determine the correct prescription. Syndrome-specific considerations are particularly important in conditions such as Dravet syndrome. Wu et al.: Clinical practice guidelines for third-generation antiseizure medications, Seizure 2026;134:13–26 NINDS: Dravet Syndrome

Investigate the cause when the result could influence care

An epilepsy-protocol MRI can look for relevant structural abnormalities, and review of original data by experienced readers may be valuable. A previous general brain MRI may not have answered every epilepsy localization question. Conversely, finding an abnormality does not prove that it is the removable source of the patient's seizures. NICE NG217: Diagnosis and assessment of epilepsy

Genetic testing can identify an explanation, clarify family implications, and sometimes inform treatment in selected patients. Its use should reflect onset, development, family information, and the likely value of a result, with counseling before and after testing. A variant of uncertain significance is not automatically the confirmed cause, and a genetic diagnosis does not guarantee that a targeted medicine exists. Krey et al.: Current practice in diagnostic genetic testing of the epilepsies, ILAE Genetics Commission, 2022

Ask what each proposed investigation is intended to change. The answer may concern a treatment choice, prognosis, family counseling, or further testing. An indiscriminate collection of expensive tests is less helpful than a sequence linked to a clear clinical question.

Medication optimization can proceed alongside specialist evaluation

The team can review seizure coverage, interactions, and effects such as sleepiness, dizziness, mood change, or cognitive difficulty while evaluating other options. The objective includes useful daily functioning as well as seizure reduction. Increasing the number of medicines is not, by itself, evidence that treatment has become more effective. Wu et al.: Clinical practice guidelines for third-generation antiseizure medications, Seizure 2026;134:13–26

The 2026 third-generation antiseizure medication guideline and its Chinese translation discuss evidence for specific drugs and circumstances. They do not establish that every newer medicine suits every patient with difficult seizures. Local authorization, age restrictions, and actual supply require confirmation. Changes and withdrawal need a clinician-directed plan because abrupt independent discontinuation can worsen seizures. 第三代抗癫痫发作药物治疗癫痫的应用指南，中译，癫痫杂志2026;12(3):222–238 NINDS: Epilepsy and Seizures

Tell the clinician which adverse effects prevent ordinary activities and which doses are difficult to take. A plan based on the regimen actually used is more informative than one based only on the prescription. The reasons a schedule is unworkable can often be discussed without abandoning the aim of better control.

A surgical referral is an assessment, not a commitment to an operation

The ILAE referral consensus supports timely evaluation once drug resistance is recognized rather than requiring years of trials of every available medicine. Assessment asks whether a relevant seizure-generating region can be treated safely and what an intervention could mean for memory, language, visual fields, movement, and other abilities. Jehi et al.: Timing of referral for epilepsy surgery evaluation, ILAE consensus, 2022

Video-EEG, MRI, and neuropsychological assessment commonly contribute. Some patients need additional imaging or invasive recordings. The investigation set should follow the localization problem; not everyone requires every possible test. An MRI without an obvious lesion does not automatically eliminate the value of a specialist surgical assessment. NINDS: Epilepsy and Seizures NICE NG217: Full guideline, updated January 30, 2025

The discussion should include uncertainty and alternatives. A recommendation to obtain more evidence may be appropriate when findings disagree. Being evaluated at a surgical center can also improve non-surgical care by refining the diagnosis and treatment plan.

Understand the different objectives of procedures and stimulation

Selected focal epilepsy may be treated by removal or ablation of particular tissue, while some complex conditions involve a disconnection strategy to limit seizure spread. Suitability depends on the distribution of disease, the seizure network, and functional risk. A smaller incision does not independently establish a better clinical choice or guarantee preservation of memory and language. NINDS: Epilepsy and Seizures

Vagus nerve stimulation, deep brain stimulation, and other approaches may be considered in appropriate patients. They require continuing follow-up and, often, programming. Reduced frequency or severity is a different outcome from complete seizure freedom. China's 2026 neuromodulation guideline discusses benefit, safety, and function; the regulatory position and patient eligibility for a particular device still need specific verification. NINDS: Deep Brain Stimulation 中华医学会：神经调控治疗癫痫临床指南2026版，中华医学杂志106(11)，期刊目录及摘要

Before agreeing to an implant, ask where programming, device checks, and urgent troubleshooting will occur. For someone returning to another country, this service arrangement forms part of the treatment decision. An implanted device is not a completed care plan by itself.

Dietary treatment needs a specialist team

Ketogenic dietary therapy may be considered for certain childhood syndromes and selected other patients when alternatives have been unsuccessful or unsuitable. It is a medical intervention requiring assessment of the disease, metabolic contraindications, nutrition, and the family's ability to carry it out. It should not be equated with a self-directed weight-loss diet that simply removes staple foods. NICE NG217: Full guideline, updated January 30, 2025

Follow-up examines seizures, weight or growth, gastrointestinal effects, and relevant laboratory findings. Food and medicine composition can affect implementation. Natural does not mean free from risk. If the household cannot maintain the proposed diet, report the difficulty so the team can consider a feasible adjustment rather than interpreting results as though the intended diet had been followed exactly.

Include mood, memory, sleep, and development in the plan

Anxiety, depression, sleep problems, and cognitive concerns can accompany epilepsy and may also relate to its cause or medicines. Explain which functional changes are most troublesome so they can be assessed. Fewer seizures accompanied by disabling daytime sedation still requires a discussion of the overall balance of benefit and harm. NINDS: Epilepsy and Seizures

In a child, developmental stagnation or loss of skills warrants timely attention. Adults may need advice about employment, relationships, and reproductive plans. Useful treatment goals can include fewer injuries, shorter recovery periods, improved alertness, and a sustainable caregiving arrangement as well as the count of seizures.

These goals should be recorded in the patient's own terms. One person may prioritize reducing unpredictable falls, another preserving language for work, and another improving a child's participation in school. Understanding those priorities helps the team explain what a proposed option can and cannot reasonably address.

Prepare an emergency plan that others can use

Caregivers should recognize the person's usual events, time them, remove nearby hazards, protect the head, and use a safe side position when feasible. Do not restrain movements or put objects into the mouth. Food, drink, or forced oral medication should not be given while the person is not fully alert. Prescribed rescue medication needs an individualized plan and appropriate training. CDC: First Aid for Seizures

A convulsive seizure reaching five minutes, or repeated seizures without recovery of consciousness, requires emergency medical action. Injury, breathing difficulty, and particular circumstances may require help earlier. In China, call 120 when emergency care is needed; elsewhere use the local emergency service. An ordinary appointment or a message to a clinician abroad must not delay treatment of an ongoing emergency. NICE NG217: Full guideline, updated January 30, 2025

The written plan should state who is expected to act and where the rescue medicine is kept. Check that school staff or other caregivers have the information relevant to their role. The existence of a prescription is insufficient if nobody nearby knows when or how it is meant to be used.

Discuss risks together with practical ways to reduce them

Uncontrolled tonic-clonic seizures are associated with epilepsy-related death, including SUDEP. The clinician should explain risk in the patient's circumstances and discuss medication use, improved seizure control, and suitable night-time care. The purpose is to agree on protective actions, not to predict that a particular person will experience a specific outcome. NICE NG217: Reducing epilepsy-related death and SUDEP risk

Swimming, bathing, heights, living arrangements, and driving require individualized planning and attention to the applicable local rules. Monitoring devices may help identify some events, but cannot guarantee prevention of every serious outcome. A response arrangement matters: the person receiving an alert needs to know what action to take.

Arrange an appropriate comprehensive service in China

The China Association Against Epilepsy publishes center assessment information and provides a map for locating services. Use these as inquiry routes, then confirm the actual adult or pediatric service, long-term video-EEG capability, imaging review, and multidisciplinary assessment relevant to the patient. A center designation does not mean that the same procedure is suitable for everyone referred there. 中国抗癫痫协会：第五批一、二级癫痫中心评审结果，2025年9月28日中国抗癫痫协会官方网站及CAAE癫痫地图入口

Send a chronological medication-trial record, a seizure diary, representative videos, and original investigations before the visit if the hospital requests them. State whether the main objective is diagnostic review, medication optimization, or evaluation of an intervention. Continue necessary prescribed treatment during travel planning. A preliminary response to an inquiry is not confirmation of eligibility for a specific therapy.

Leave with an explanation of the next decision

Ask the clinician to separate what continues now, what information is still needed, and which choices depend on forthcoming results. If an operation is not currently recommended, clarify whether localization is incomplete, functional risk is unacceptable, or another approach is more suitable. These reasons determine what could usefully be reconsidered later.

At follow-up, provide comparable seizure and adverse-effect records rather than only saying better or worse. After a medicine change, procedure, or implant, identify the intended review point and the clinician responsible after returning home. Comprehensive care develops as evidence and life circumstances change; the patient should be able to understand the purpose of each adjustment.