Abstract
Sharma S, Chen Z, Rychkova M, Dunne J, Lee J, Lawn N, Kwan P. Epilepsy Behav. 2022;131(Pt A):108664. doi:10.1016/j.yebeh.2022.108664
Objective: Patients with epilepsy not uncommonly self-discontinue treatment with antiseizure medications (ASM). The rate, reasons for this, and consequences have not been well studied. Methods: We analyzed self-discontinuation of ASM treatment in patients with recently diagnosed epilepsy via review of clinic letters and hospital correspondence in a prospective cohort of first seizure patients. Results: We studied 489 patients with newly diagnosed and treated epilepsy (median age 41, range 14-88, 62% male), followed up for a median duration of 3.0 years (interquartile range [IQR]: 1.2-6.0). Seventy-eight (16.0%) self-discontinued ASM therapy after a median treatment duration of 1.4 years (IQR: 0.4-2.9), and after a median duration of seizure freedom of 11.8 months (IQR: 4.6-31.8). Patients commonly self-discontinued treatment due to adverse effects (41%), perception that treatment was no longer required (35%), and planned or current pregnancy (12%). Patients who self-discontinued were less likely to have epileptogenic lesions on neuroimaging (hazard ratio [HR] = 0.44, 95% confidence interval [CI]: 0.23-0.83), presentation with seizure clusters (HR = 0.32, 95% CI: 0.14-0.69) and presentation with tonic-clonic seizures (HR = 0.36, 95% CI: 0.19-0.70). Patients with shorter interval since the last seizure (HR = 0.76, 95% CI: 0.66-0.86) were more likely to self-discontinue treatment. Sleep deprivation prior to seizures before diagnosis (HR = 1.80, 95% CI: 1.05-3.09) and significant alcohol or illicit drug use (HR = 2.35, 95% CI: 1.20-4.59) were also associated with higher rates of discontinuation. After discontinuation, 51 patients (65%) experienced seizure recurrence, and 43 (84%) restarted treatment. Twenty-two patients (28%) experienced a seizure-related injury after treatment discontinuation. Significance: Self-initiated discontinuation of ASM treatment was not uncommon in patients with newly treated epilepsy. Reasons for discontinuation highlight areas for improved discussion with patients, including the chronicity of epilepsy and management strategies for current or potential adverse effects.
Commentary
The consequences of seizures are serious. The primary job of epileptologists and other members of the treating team is to prevent as many seizures as possible. Although cutting-edge treatments such as neurostimulation, surgery, and new drugs often dominate discussion at epilepsy congresses, the central pillar of medical care for patients with epilepsy remains existing anti-seizure medications (ASMs). If every patient with epilepsy received appropriate ASMs, much of the burden of seizures would be lifted. Three steps are needed to accomplish this.
First, effective ASMs must be discovered, developed, and manufactured. Although there is room for improvement, more than 25 ASMs are currently available around the world. 1
Second, individuals with epilepsy must be identified and ASMs prescribed to them. This task makes up much of the time of the practicing epileptologist/neurologist, and a substantial infrastructure has been built up and maintained to accomplish this, although provision of ASMs in many developing countries remains inadequate. The benefits are clear, as approximately 70% can be made seizure-free with medications alone. 2
Third, the prescribed medication must be taken regularly. This step is hardly less important that the first two. Surprisingly little research has gone into finding ways to accomplish it more effectively.
The paper under discussion by Sharma and colleagues, 3 an examination of patients who self-discontinued ASMs from a prospective registry of first-seizure clinics, steps admirably into the breach and opens several interesting avenues for further study. Its main impact is to show how little attention has been paid to the problem of patient self-discontinuation of ASMs, and how much is left to do.
The patients in the study registry were prospectively enrolled in Western Australia between 1999 and 2016. Recruited from a first seizure clinic, patients had received a new diagnosis of epilepsy and were treated with ASMs for the first time. Just under 10% were excluded due to absent follow-up, as were patients whose ASMs were stopped by a neurologist. Within the remaining group, the authors sought to determine the rate of patient-initiated ASM discontinuation, characterize the reasons for ASM cessation, and identify demographic and epilepsy characteristics associated with ASM self-discontinuation. In addition, the impact of discontinuation was examined.
Overall, 78 (16%) of 489 patients self-discontinued ASMs, which, as the authors recognize, likely represents an underestimate, since patients excluded due to lack of follow-up likely discontinued at a higher rate. These numbers also do not include patients who declined presciption despite neurologist recommendation.
Self-discontinuation occurred at a median time of 1.4 years after prescription. Usually, it was the first prescribed ASM that was self-discontinued, with cessation rates not much affected by which ASM was prescribed. Most self-discontinuing patients were seizure-free, with a median seizure-free duration of 11.8 months.
Based on information in patient charts, the authors summarily categorized the patients’ stated explanations. The 3 most common reasons were medication side effects (41%), belief that medication was no longer needed (35%), and concerns regarding pregnancy (12%).
Factors associated with lower self-discontinuation were the presence of an epileptogenic lesion on imaging, tonic–clonic seizures, seizure clusters, and prolonged seizure-free intervals. Patients with seizures associated with sleep deprivation or who consumed more alcohol or drugs discontinued at a higher rate. Following discontinuation, 65% had further seizures, and 55% eventually restarted ASMs. Seizure-related injuries (often minor) occurred in 28% of discontinuing patients. Although there were no reported cases of SUDEP, 1 patient died following aspiration pneumonia, and 4 patients had motor vehicle accidents caused by seizures.
What conclusions or questions can we draw from such a study? First, we must keep in mind that the findings apply to a specific population and the behavior under investigation is influenced by a host of individual factors, cultural beliefs, and prevailing attitudes. It will be necessary to study other populations.
Clearly, medication self-discontinuation is an important problem. The authors note that their rates are comparable to those found in the reports of many ASM trials, usually without comment by investigators. Although many patients reported side effects as the primary cause for self-discontinuation, this explanation seems incomplete since they often tolerated the medications for months or years before giving them up. What factors drove their decision? And when they reported a belief that the medications were “no longer required,” what was this founded on? There are surely many answers to these questions. An interesting finding is that patients with structural lesions are less likely to stop taking ASMs; is there something in the knowledge of having a visible brain abnormality that is more convincing than the vain exhortations of a neurologist?
Unfortunately, the complexity of these questions lies beyond the power of a chart review. Patrick Kwan, the study’s senior author, famously brought the world’s attention to the 30% of patients with pharmacoresistant epilepsy
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; hopefully the current study will focus future efforts on the 20% who stop taking ASMs. Detailed questionnaire studies or qualitative research are needed to better understand this patient population and address their concerns prior to self-discontinuation. One suspects that the problem could be addressed with more effective individualized communication, although recent world events have highlighted the limits of rational discourse around health decisions. We would also do well not to assume that patients are “wrong” when they choose to stop ASMs. To better help epilepsy patients, it is essential that we understand them better, and that we help them better understand our recommendations. To conclude with the words of one person with epilepsy from the qualitative literature: …[Y]ou feel like saying, “Well what’s the basis of the approach for this drug?” And they don’t tell you. I mean [my doctor] is very good and he gives me proper information sheets, but I have no idea of what is the, not philosophy, the thought process, whatever, behind it, you know of the approach…. I have no idea of where they’re coming from to come up with this drug, what they think it’s interacting with, why they think it works. And I personally would like to know that…
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