People living with long-term uncontrolled epilepsy often face a paradox at the heart of their care: they may be receiving too much medication and too little hope at the same time. The paper, an expert review based on decades of clinical observation, frames these pitfalls as avoidable and offers concrete strategies for overcoming them.
The authors define therapeutic nihilism as treatment reticence in patients or physicians, which can result in the underuse of potentially effective therapies. Its mirror image, overtreatment, is defined as an unnecessary or excessive drug load that leads to suboptimal management of the risk-to-benefit ratio of antiseizure medications, or ASMs. Crucially, the review stresses that these are not mutually exclusive.
The stakes of uncontrolled epilepsy are high. The review notes that individuals who do not achieve seizure freedom encounter more stigma, suffer poorer quality of life and a lack of social support, struggle with impaired cognition, and face an increased risk of comorbidities and death from accidents or sudden unexpected death in epilepsy, known as SUDEP. Persistent symptoms require continual clinical follow-up, which itself becomes a burden of illness, and the unpredictable timing of seizures can induce anxiety. As the chances of complete seizure control are recognized to diminish with each ASM failure, optimism becomes harder to maintain for both patients and their healthcare providers, feeding a cycle of discouragement and helplessness.
Why do clinicians fall into these traps? The authors identify inadequate communication as often the foundation, compounded by internal biases, lack of insight, or out-of-date knowledge. Overtreatment is more likely after failure of multiple ASMs, or when there is a clinical perception of a negative prognosis, a high seizure burden, or concern about injuries and SUDEP. Unrealistic patient expectations or pressure from patients and caregivers can push physicians into being seen to “do something.” Misdiagnosis also plays a role: accurate diagnosis and classification of epilepsy is not always easy, and misdiagnosis is relatively common, substantially reducing the likelihood that an inappropriate treatment will succeed. Fear of inducing seizures by reducing or discontinuing ASMs can likewise keep ineffective or poorly tolerated drugs on board indefinitely.
Therapeutic nihilism has its own distinct drivers. Physician undertreatment and feelings of hopelessness may stem from underestimation of seizure impact, disappointing experiences with previous ASM treatments, perceived skepticism from family or caregivers—especially during the transition from pediatric to adult care—and fear of adverse effects from new treatments. The social consequences of ongoing seizures, such as medical retirement or placement on social security benefits, can cause patients or caregivers to withdraw pressure to modify treatment. Time pressures in the clinic may further deter appropriate discussions about further therapeutic options. The result is treatment reticence that reduces access to potentially more beneficial ASMs or to adequate doses.
Against this pessimistic picture, the review marshals evidence that the outlook is better than commonly believed. A frequent misperception holds that seizure freedom is highly unlikely after treatment failure with two ASMs, but the authors state this is not universally borne out by the data. In a study at the Kork Epilepsy Center, 60% of patients achieved long-term seizure freedom, with 70% becoming seizure-free after using a maximum of five ASMs. Approximately half of those with newly diagnosed epilepsy reach seizure freedom with their first drug, and for most of the remaining patients, polytherapy will likely be initiated. The emergence of newer ASMs for focal seizures and for specific syndromes such as Dravet syndrome suggests the treatment landscape continues to improve.
Some of the newer agents deserve particular attention, the authors argue. When patients experience disabling or life-threatening seizures, early use of particularly efficacious and recently introduced ASMs such as cenobamate or fenfluramine may be viewed as critical. Indirect comparisons with older ASMs have shown these drugs demonstrate superior and sustained efficacy with similar tolerability, and cenobamate was found more effective than perampanel, eslicarbazepine acetate, lacosamide, brivaracetam, and zonisamide in a systematic literature review of focal seizure treatments. Recent studies showed adjunctive cenobamate effectively reduced seizures and allowed reduction or elimination of polytherapy beyond what has been reported in trials of older ASMs. Yet these newest drugs may be used less frequently simply because of a lack of awareness or knowledge regarding their improved efficacy.
The practical strategies the review proposes begin with getting the basics right. Proper diagnosis and appropriate choice of first-line treatment are critical: ensuring an accurate epilepsy classification enhances ASM efficacy and helps avoid drugs that may provide incomplete efficacy or even worsen epilepsy. At initial diagnosis, monotherapy should start at low doses and be titrated to target. As treatment escalates, dose changes should be guided by clinical response and by individual patient characteristics and symptoms rather than blind adherence to generally recommended doses or serum concentration ranges—an approach the authors call honoring the individual’s own therapeutic range. Clear assessment of efficacy after adding a new ASM requires objective knowledge of seizure frequency before and after, and if the new drug is ineffective at optimized doses, it should be withdrawn. The risk-to-benefit ratio of the regimen should be reassessed regularly, with a “plan B” developed and shared with the patient as a backup.
The authors also highlight cognitive and psychological tools for clinicians. Combining nonanalytical and reflective reasoning may help in choosing the most effective treatment, while consciously identifying and re-framing emotions and emphasizing one’s professional expertise may reduce bias. They describe omission biases, in which a physician fearful of anticipated regret avoids actions that carry risk of harm, and commission biases, in which a provider fears that inaction may be viewed as irresponsible. Physicians should also remain aware of how variations in patient characteristics—race, sex, socioeconomic status, comorbidities—affect treatment decisions and responses. Consideration of alternative modalities such as epilepsy surgery, often neglected in drug-refractory cases, is described as vital, and modifying concomitant medications or reducing drug load may improve both tolerability and effectiveness.
The review closes with a message aimed squarely at restoring realistic optimism. Seizure freedom remains an important and worthwhile goal, and patients and families should know that the increased therapeutic options available today can make seizure freedom possible even after previous ASM failures or in the context of a challenging prognosis. Communication with patients and families is key, including outlining the risks and benefits of treatment changes; more hazardous seizures may justify more active management, with escalation presented as a way of actively minimizing risk. Conveying accurate seizure freedom rates, the authors argue, is vital for motivating patients and caregivers, while continued vigilance about the contribution of every ASM in a regimen guards against creeping overtreatment. When seizure reduction or freedom is finally achieved in previously refractory patients, the resulting ability to reduce or eliminate concomitant medications can bring an even greater improvement in quality of life—evidence, the authors suggest, that neither too many drugs nor too little hope should ever be accepted as the final word in chronic epilepsy.
Subject of Research: Overtreatment and therapeutic nihilism in the management of chronic epilepsy
Article Title: Overtreatment and therapeutic nihilism in chronic epilepsy: a call to action!
Article References: Steinhoff, B. J., & Leach, J. P. (2026). Overtreatment and therapeutic nihilism in chronic epilepsy: a call to action!. Acta Epileptologica, 8(1), Article 18. https://doi.org/10.1186/s42494-026-00257-3
Image Credits: AI Generated
DOI: 10.1186/s42494-026-00257-3
Keywords: epilepsy, antiseizure medications, drug-resistant epilepsy, overtreatment, therapeutic nihilism, seizure freedom, SUDEP, cenobamate, polytherapy, individualized care, clinical review, therapeutic
News Source: Kendall Mcintyre. (October 29, 2026). Overtreatment and Therapeutic Nihilism: Twin Pitfalls in Chronic Epilepsy Care. Scienmag.
