Stay or Go: Decision-Making Surrounding Antiseizure Medication Discontinuation

Commentary

Deciding who to treat, how intensively, and for how long represent core aspects of epilepsy care. Fortunately, 2/3^rd of patients achieves seizure control on antiseizure medications (ASMs). These patients may reasonably ask, “Do I need ASMs forever?” Guidelines encourage considering this within an individualized risk-benefit discussion. ¹

Still, data limitations make it difficult to draw clear conclusions about which patients to consider weaning off ASMs and when. Imperfect evidence and variability regarding physician practices^2,3 set up questions about how often patients are discontinuing ASMs in reality. For example, in one study of 338 patients from three outpatient clinics in Germany, ⁴ only 12% of adults who were seizure-free at least two years opted to completely discontinue medication, and another 7% pursued at least a 25% dose reduction. Predictors of continuing medication without a dose reduction included tonic-clonic seizures, prior failed attempts at discontinuation, and higher doses.

Ilyas-Feldmann and Graf et al ⁵ recently followed up those findings with several additions. They further distinguished between predictors of neurologist recommendations as opposed to patient decisions, in addition to adding more detailed patient questionnaires. There were 196 analyzed adults who were seizure-free for at least 2 years on monotherapy from 10 neurologists. Neurologists recommended complete discontinuation in 76 (39% of 196), of whom only 7 discontinued (9% of 76) and 11 agreed to reduce their dose by at least 25% but not fully discontinue. Neurologists also recommended a dose reduction of at least 25% in another 34 patients, of whom 11 agreed to do so.

Such findings align with prior work,^6,7 that patients (and neurologists^2,3) never say never but are often reluctant to discontinue medication. Prior work has shown that even the lowest-risk patients still on ASMs uncommonly discontinue ASMs. ⁷ ASMs do have many potential downsides such as side effects, cost, refills, monitoring, etc. Other motivators to discontinue medication include fear of long-term organ injury, belief in complementary and alternative medication, those with lesser concern about seizure consequences, or interpreting a seizure-free period to mean that their epilepsy has been “cured.” ⁸ Still, Ilyas-Feldmann and Graf et al highlight the many factors that may push a patient towards continuing their ASM such as a feeling of safety while medicated or fear of seizures or losing driving or work ability if unmedicated, as expected. ⁸

An interesting byproduct of this work is the examination of how neurologist and patient viewpoints or motivations may diverge.

Neurologists in this study appeared more liberal than their patients in recommending ASM discontinuation. As above, among 196 patients, the neurologist recommended reduction or discontinuation in 110 (76 + 34), although the patient followed suit in only 29. Though it could work the other way as well—those patients most in favor of discontinuing could have simply done so on their own with no perceived need to follow-up with their neurologist and thus would not be captured in this study.

Adjusted predictors of neurologists recommending dose reduction or discontinuation included longer seizure-free duration and more years of neurologist experience, and in univariable analysis the patient being in a relationship. Neurologists also qualitatively cited shorter seizure-free durations as favoring continuation. In contrast, adjusted predictors of patients pursuing dose reduction or discontinuation included SHORTER seizure-free duration and lack of tonic-clonic seizures, and in univariable analysis the patient being SINGLE. To the neurologist, longer seizure-free periods likely signal a patient at lower risk of relapse. Though perhaps to the patient, longer seizure-free periods may increasingly favor inertia, or a “don’t fix what isn’t broken” mentality. Neurologists also tended to provide qualitative reasons that spoke more so to seizure probability (eg, seizure-free duration, structural etiology), whereas patients tended to frame reasons favoring continuation in terms of functional impact (eg, driving, work, seizure severity). Additionally, to the clinician, being in a relationship could be a reassuring feature regarding the degree of patient supervision, whereas to the patient having a partner/spouse could serve as a guardrail dissuading them from considering discontinuation. Neurologists in this study also cited the patient being on a minimal ASM dose as a reason to continue it, presumably with reasoning that a low dose should cause little harm. Though, a low dose could be just as easily interpreted as a reason favoring discontinuation, as a marker of easier to control epilepsy. These divergent or two-sided arguments (seizure-free duration, relationship status, dose) serve as useful reminders that we as clinicians should always be cognizant that our interpretation of facts and circumstances may not align with the patient's interpretation of those same data. Only by explicit dialogue with the patient can we best understand what patient features may argue for or against medication.

Another interesting finding is what was NOT associated with discontinuation, including a wide variety of questionnaires measuring seizure severity, side effects, anxiety, personality type, and sociodemographics. Several possibilities exist such as type II error or else imperfect scale reliability (eg, the Liverpool Adverse Events Profile measures bothersome symptoms, but not necessarily exactly whether the patient is having side effects from their ASMs). Though another possibility could be that such questions miss the major sources of variability in a patient's inherent attitudes about how effective their medication is or beliefs about medications in general or how aggressive they wish to approach their medical care overall. Future studies can broaden the array of patient-centered factors that could drive decision-making.

One major unanswered question related to this work is: What was the content and quality of shared decision-making during visits leading to such choices? General medical literature struggles to specify a single universal definition of what makes a “good” decision process. Though consensus suggests that high-quality decision processes involve the patient having adequate relevant knowledge (eg, risks, benefits) and making a choice concordant with their personal values, regardless of whether the outcome was “good.” ⁹ Prior work has shown that patients may make overly conservative decisions based upon likely falsely exaggerated beliefs regarding recent seizure-freedom suggesting that their ASM is completely responsible and seizures would be inevitable if they were to discontinue. ¹⁰ Thus, the degree to which conservative decisions occur due to cognitive biases or misinformation versus appropriate counseling remains understudied, and these data do not evaluate the degree to which shared decision-making occurred (eg, patients recognizing a decision is to be made and were involved in that decision, etc).

Much work remains to be done informing optimal counseling techniques and identifying appropriate candidates for discontinuation. The present work by Ilyas-Feldmann et al opens the door for additional research further exploring these difficult but important questions to optimize both decision-making processes and outcomes.