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Overview of the management of epilepsy in adults

Overview of the management of epilepsy in adults
Author:
Steven C Schachter, MD
Section Editor:
Paul Garcia, MD
Deputy Editor:
John F Dashe, MD, PhD
Literature review current through: Sep 2023.
This topic last updated: Apr 25, 2022.

INTRODUCTION — The management of patients with epilepsy is focused on three main goals: controlling seizures, avoiding treatment side effects, and maintaining or restoring quality of life. Clinicians should assist in empowering patients with epilepsy to lead lifestyles consistent with their capabilities [1,2].

The optimal treatment plan is derived following an accurate diagnosis of the patient's seizure type(s), an objective measure of the intensity and frequency of the seizures, awareness of medication side effects, and an evaluation of disease-related psychosocial problems. A working knowledge of available antiseizure medications (ASMs), including their mechanisms of action, pharmacokinetics, drug-drug interactions, and adverse effects, is essential.

It is usually appropriate to refer the patient to a neurologist when establishing a diagnosis and formulating a course of treatment. Referral to an epilepsy specialist may be necessary if there is doubt about the diagnosis and/or if the patient continues to have seizures.

The overall approach to management of a patient with seizures is reviewed here. Evaluation of the patient who has had a first seizure and the pharmacology of specific ASMs are discussed separately. (See "Evaluation and management of the first seizure in adults" and "Initial treatment of epilepsy in adults" and "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

CLASSIFICATION — The first step in designing a treatment plan is to classify the patient's seizure type(s) using the framework of the International League Against Epilepsy (table 1) [3-6]. Seizure types and epilepsy syndromes are classified primarily upon clinical grounds, assisted by laboratory, neurophysiologic, and radiographic studies. Seizure type has important implications in the choice of ASMs. Accurate classification requires a full history from the patient and reports from observers who have witnessed actual seizures. (See "ILAE classification of seizures and epilepsy".)

Patients may be better able to describe their seizure symptoms after reading published seizure descriptions, which in turn may improve the clinician's ability to categorize the seizure type and to plan a successful therapeutic approach [7]. Many patients experience more than one type of seizure (eg, focal seizures and secondarily generalized seizures).

Pointed questions may be necessary to reveal behaviors or environmental factors that contribute to the incidence of seizures. These "seizure triggers," such as sleep deprivation, alcohol intake, and stress, may be modifiable. Thus, taking steps that limit exposure to these triggers usually enhances the benefits of ASM therapy.

There are two broad categories of seizures: focal (or partial) and generalized (table 1 and table 2). Focal seizures involve only a portion of the brain, typically part of one lobe of one hemisphere. A focal seizure can be associated with impairment of awareness (previously called complex partial seizure) or no impairment of awareness (previously called simple partial seizures). A focal seizure can evolve over seconds into a bilateral tonic-clonic seizure, also referred to as a secondarily generalized seizure. (See "Evaluation and management of the first seizure in adults", section on 'Types of seizures'.)

ANTISEIZURE MEDICATION THERAPY

When to start antiseizure medication therapy — Immediate antiseizure medication (ASM) therapy is usually not necessary in individuals after a single seizure, particularly if a first seizure is provoked by factors that resolve. ASM therapy should be started in patients who are at significant risk for recurrent seizures, such as those with remote symptomatic seizures. ASM treatment is generally started after two or more unprovoked seizures, because the recurrence proves that the patient has a substantially increased risk for repeated seizures, well above 50 percent.

The issues to be considered in deciding when to start ASM therapy are discussed in detail separately. (See "Initial treatment of epilepsy in adults", section on 'When to start antiseizure medication therapy'.)

ASM therapy is not necessarily lifelong. (See 'Discontinuing antiseizure medication therapy' below.)

Choosing an antiseizure medication — Approximately half of patients with a new diagnosis of epilepsy will become seizure free with the first ASM prescribed [8,9]. Tolerability of side effects is as important as efficacy in determining the overall effectiveness of treatment. No single ASM is optimal for every patient. The selection of a specific ASM for treating seizures must be individualized considering:

Drug effectiveness for the seizure type or types (table 3 and table 4) [10]

Potential adverse effects of the drug (table 5 and table 6)

Interactions with other medications

Comorbid medical conditions, especially, but not limited to, hepatic and renal disease

Age and gender, including childbearing plans

Lifestyle and patient preferences

Cost

In general, enzyme-inducing ASMs (eg, phenytoin, carbamazepine, phenobarbital, primidone, and less so, oxcarbazepine and topiramate) are the most problematic for drug interactions with warfarin and oral contraceptive therapy, as well as certain anticancer and anti-infective drugs (table 7). Specific interactions of ASMs with other medications may be determined using the Lexicomp drug interactions tool.

Issues to consider in selecting a specific ASM are discussed in detail separately. (See "Initial treatment of epilepsy in adults", section on 'Selection of an antiseizure medication'.)

Subsequent drug trials — Seizures in approximately half of patients with a new diagnosis of epilepsy are successfully treated with the first ASM prescribed [8,9,11]. Treatment failure may result from breakthrough seizures or drug intolerance. At this point, a second drug trial should be attempted. When the initial drug failure is due to adverse effects, the second drug trial will be successful in approximately half of patients [12,13]. Substantially fewer patients (approximately 10 to 20 percent) will have a successful second drug trial if the initial failure was due to lack of efficacy. Other factors that decrease the likelihood of success include younger age, female gender, high generalized tonic-clonic seizure burden, and the presence of structural abnormalities on computed tomography (CT) or magnetic resonance imaging (MRI) [13].

Similar factors are considered when a second ASM is chosen as when the first was selected (see 'Choosing an antiseizure medication' above and "Initial treatment of epilepsy in adults"). However, the clinician may also choose to select an ASM with a somewhat different mechanism of action (table 8) in hopes that efficacy and/or tolerance will be improved compared with the first drug used. It remains important to choose a drug with demonstrated efficacy for the patient's seizure type [10] and to avoid drugs that may precipitate or aggravate seizures; the latter is most relevant in patients with genetic generalized epilepsies such as juvenile myoclonic epilepsy or absence epilepsy. (See "Juvenile myoclonic epilepsy", section on 'Antiseizure medications to avoid' and "Childhood absence epilepsy", section on 'Drugs to avoid'.)

Except in the case of a serious adverse event from the first ASM, the second medication is typically increased to therapeutic levels before the first agent is reduced in order to prevent a flurry of seizures or status epilepticus during the switch-over period. The second ASM is gradually titrated up slowly to effect (control of seizures) or to toxicity (side effects). However, patients should expect a temporary increase in side effects during the overlap period that will likely abate when the first ASM is subsequently tapered off.

Combination therapy — When possible, it is preferable to maintain a patient on a single ASM. This increases the probability of compliance, provides a wider therapeutic index, and is more cost effective than combination drug treatment. Monotherapy is also associated with fewer idiosyncratic reactions and a lower incidence of teratogenic effects. Combination therapy can be associated with drug interactions between ASMs (table 9A-C), making it difficult to dose and monitor patients.

This conventional wisdom is only partly supported by published data, which give conflicting information regarding the risks and benefits of mono- versus polytherapy:

In one large case series of 809 patients with refractory epilepsy, rates of adverse events did not differ between patients on poly- versus monotherapy [14].

In one clinical trial, rates of adverse events were similar among 157 patients randomized to adjunctive treatment versus alternative monotherapy, and rates of seizure remission were also similar (16 versus 14 percent) [15].

A randomized, double-blind study that compared carbamazepine monotherapy with combination therapy with carbamazepine and valproate found no significant difference in neurotoxicity between the two groups [16].

In one epidemiologic survey, polytherapy was associated with lower quality of life and lower rates of employment compared with patients on monotherapy [17].

There are few controlled studies comparing different drug combinations, and virtually every possible combination of ASMs has been tried. A 2011 meta-analysis of 70 randomized controlled trials of ASMs administered as add-on therapy in patients with refractory focal epilepsy found that differences in efficacy were of too small magnitude to allow a conclusion about which ASM is more effective as adjunctive therapy [18]. In a randomized, double-blind trial of pregabalin versus levetiracetam as add-on therapy in 509 patients with refractory focal seizures published subsequent to this analysis, 60 percent of patients in each arm achieved a ≥50 percent reduction in 28-day seizure rate, and tolerability was similar [19].

In the absence of comparative data from clinical trials, it makes sense to choose an add-on drug that has a different mechanism of action (table 8) and a different side-effect profile than the first ASM (table 5 and table 6) [20-22]. In this way, it is hoped that efficacy can be maximized and side effects minimized [14]. The benefit of this approach is largely theoretical, supported by limited observational data but not well tested prospectively [23]. However, there is some anecdotal evidence that synergism between ASMs can occur [24-28]. As an example, a post hoc analysis of pooled data from randomized trials suggested greater benefit and less toxicity when lacosamide, a sodium channel-blocking drug, was used in combination with non-sodium channel-blocking drugs [28].

Seizure remission is achieved with combination therapy in only a small percentage (10 to 15 percent) of patients whose seizures were not controlled by monotherapy [12,29,30]. One retrospective chart review suggested that while two concurrent ASMs might provide efficacy over monotherapy, use of three ASMs did not provide further benefit over two [27].

While the chances of treatment success diminish incrementally with each successive drug trial [31], two studies suggest a value in pursuing further drug trials [29,30]. In one center, 15 percent of patients whose seizures continued despite two prior ASM trials subsequently became seizure free with ASM therapy [30]. In another, 28 percent of patients with a history of uncontrolled seizures for five or more years were subsequently controlled on ASMs [29]. In some cases, response to treatment occurred with a fourth or fifth drug trial. Both studies found that the number of previous failed trials was a negative prognostic indicator, and a history of status epilepticus, younger age at intractability, underlying intellectual disability, longer duration of epilepsy, and symptomatic epilepsy were each a negative predictor in one of the two studies.

Overall, up to 80 percent of patients can become seizure free on ASM treatment [13,29-31].

Side effects of therapy — During the first six months of treatment, systemic toxicity and neurotoxicity cause ASM failure to the same degree as lack of efficacy against seizures (table 5 and table 6). Serum levels that are associated with neurotoxicity vary from patient to patient, and toxicity can occur even when measured levels are considered to be within the appropriate therapeutic range.

The usual strategy in patients experiencing peak-level side effects from a specific drug is to alter the medication regimen or treatment schedule to minimize side effects; one alteration may be to spread the medication over more doses throughout the day. The clinician should attempt to correlate serum drug concentrations with the patient's side effects before abandoning that medication. Specifically, obtaining levels when a patient is experiencing side effects and comparing them with levels obtained when the patient is free from symptoms can be helpful in the management of some patients.

It can be also be useful to refer to the patient's seizure calendar in planning the timing of drug levels in an attempt to prove a cause-and-effect relationship between peak levels and side effects. As an example, in a patient who experiences seizures only at night but who has side effects in the afternoon from their morning dose of ASMs, shifting part of the morning dose to the bedtime dose may eliminate these side effects while improving seizure control.

Specific adverse reactions — Many side effects of ASMs specific to individual medications are reviewed in detail separately (see "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects"). Some severe reactions that are common to more than one medication include the following:

An increased risk of suicidality has been linked to several ASMs in randomized placebo-controlled studies of patients with epilepsy, according to a January 2008 US Food and Drug Administration (FDA) report [32]. The elevated risk (0.43 versus 0.22 percent) was observed as early as one week after starting medication and continued through the 24 weeks of study observation. The effect was consistent in the 11 ASMs studied, and the FDA considers this risk likely to be shared by all ASMs. A 2009 literature review estimated that the overall standardized mortality ratio for suicide was 3.3, and that this increased risk appeared to be present among most subgroups of individuals with epilepsy [33]. In addition, a 2019 Danish case-control study found that the use of ASMs was associated with an increased risk of suicide; the increased risk was not explained by a history of suicidality, nor by a familial disposition to psychiatric disorders [34].

Other studies have challenged these findings. A 2021 systematic review and meta-analysis identified five ASMs (eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate) studied in 17 randomized controlled trials and found that the risk of suicidal ideation was not increased overall nor for any individual drug [35]. A case-control study found that only some of the newer ASMs (levetiracetam, topiramate, vigabatrin) were associated with a risk of self-harm or suicide, while older and other newer ASMs were not [36]. Another study based in the United Kingdom found that the magnitude of suicide risk associated with ASM use varied according to the underlying etiology and was not elevated in patients with epilepsy [37]. However, the clinical studies evaluated by the FDA that led to the original warning were performed in patients with epilepsy.

Despite being somewhat controversial, the 2008 FDA clinical advisory remains in effect. Therefore, clinicians prescribing ASMs should identify a current or past history of depression, anxiety, and suicidal ideation or behavior in their patients [38-40]. Patients taking ASMs should be monitored for emergence or worsening of suicidal ideation or depression. Patients and families should be encouraged to call their clinician if they experience any symptoms of depression [38,41]. (See "Comorbidities and complications of epilepsy in adults", section on 'Screening'.)

A suggested approach to the assessment of suicidality in adults is discussed separately. (See "Suicidal ideation and behavior in adults", section on 'Suicidal ideation and behavior'.)

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) are rare but severe idiosyncratic reactions, characterized by fever and mucocutaneous lesions, that have been associated with the use of carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, zonisamide, lamotrigine, and (less commonly) other ASMs [42-45]. The period of highest risk is within the first two months of use [46]. The risk may be higher in patients with HLA-B*1502 allele, which occurs almost exclusively in patients of Asian ancestry. The FDA recommends screening such patients for this allele prior to starting carbamazepine, oxcarbazepine, and possibly phenytoin [47]. By extension, Asian patients starting eslicarbazepine, an active metabolite of oxcarbazepine, should also be screened. Because cross-hypersensitivity to other ASMs is common, patients who experience this reaction should subsequently be treated with nonaromatic ASMs (eg, valproate, topiramate), which have a lower risk of this reaction. In one case series, the latter medications were well tolerated when prescribed as alternative ASMs to patients who experienced SJS or TEN in association with an aromatic ASM [45]. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects" and "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)

Reduced vitamin levels have also been described in patients taking ASMs, especially enzyme-inducing drugs. In one study, subnormal folate levels were reported in 16 percent of patients on ASMs (primarily in patients taking carbamazepine, gabapentin, phenytoin, or primidone) [48]. While vitamin B12 levels were lower on average in patients taking ASMs (particularly in patients taking phenobarbital, pregabalin, primidone, or topiramate), the frequency of subnormal B12 levels was not significantly different in patients compared with controls. In patients with low B12 levels, vitamin supplementation yielded normal levels within three months. Elevated plasma homocysteine occurs with increased frequency in patients on long-term enzyme-inducing ASMs and may reflect deficiency of folate, vitamin B6, and/or vitamin B12 [49]. (See "Clinical manifestations and diagnosis of vitamin B12 and folate deficiency" and "Treatment of vitamin B12 and folate deficiencies".)

Enzyme-inducing ASMs have been associated with an increased prevalence of hyperlipidemia and other markers of vascular risk [49,50]. Lipid screening is therefore suggested in patients who require long-term therapy with enzyme-inducing drugs. (See "Screening for lipid disorders in adults".)

Retrospective data suggest that people with epilepsy who use ASMs have an increased risk of cardiovascular events [51]. However, it is unclear whether enzyme-inducing ASMs are associated with a greater risk of cardiovascular disease than nonenzyme-inducing ASMs, as the evidence is inconsistent [51,52].

Bone loss has also been described in patients receiving long-term ASMs. (See "Antiseizure medications and bone disease".)

Maximizing the likelihood of a successful outcome

Titration and monitoring — Some general principles to consider when starting an ASM include [53-55]:

Start treatment with a single drug (monotherapy).

In general, the strategy is to gradually titrate to the highest dose that is tolerated and/or produces seizure freedom (start low and go slow). The concept is to slowly titrate up to a dose that causes persistent or recurrent side effects and then to titrate back down to a previously tolerable dose.

Using this approach, there is only one decision to make if breakthrough seizures occur, which is to add a second seizure medication; raising the dose to achieve seizure control is not a good option because the patient previously had persistent/recurrent side effects at the next dosage level up. This strategy is especially helpful with ASMs that have easily identified, dose-related side effects and a narrow therapeutic index.

Monitor treatment regularly. At regular office visits, clinicians should ask and record seizure frequency and medication side effects [3].

The recommended initial dose for individual ASMs and a potential titration schedule are presented separately. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

Regular follow-up visits should be scheduled to check drug concentrations, blood counts, and hepatic and renal function, when indicated. These visits are also used to address concerns the patient may have about taking the medication and possible side effects, or psychosocial aspects of their disorder. It may be useful to obtain drug levels at least yearly, including in patients who are not having seizures and not undergoing medication dose changes.

Drug levels can be helpful in the management of ASMs [56,57]:

To establish an individual therapeutic concentration range when a patient's seizures are in remission

To assist in the diagnosis of clinical ASM toxicity (see 'Side effects of therapy' above)

To assess adherence (see 'Nonadherence with antiseizure medication therapy' below)

To guide dose adjustments, particularly in the setting of drug formulation changes, breakthrough seizures, when an interacting medication is added to or removed from a patient's regimen, or during pregnancy

Total serum levels alone should not necessarily be taken at face value. As an example, unbound ("free") serum levels of phenytoin must be checked in patients who have low albumin levels or who are taking other drugs that are tightly protein bound; free levels should be multiplied by 10 to approximate the desired total serum level for agents that are typically approximately 90 percent protein bound. It is also important to measure free drug levels in pregnant women taking ASMs that are bound significantly to serum proteins. (See "Management of epilepsy during preconception, pregnancy, and the postpartum period", section on 'Antiseizure medication monitoring and dose adjustment'.)

Serum drug concentrations may fluctuate in compliant patients due to laboratory error, change in drug formulation (generic to brand, reverse, or generic-to-generic switch), drug interactions, variable absorption, and variable pill potency (eg, some pills stored in warm, humid places may have reduced effectiveness). Fluctuating ASM levels at different points in the menstrual cycle may play a role in breakthrough seizures in women with catamenial epilepsy. (See "Initial treatment of epilepsy in adults", section on 'Catamenial epilepsy'.)

Patient education — Before treatment is initiated, the clinician needs to begin a dialogue with the patient and family to increase their understanding of epilepsy and their ability to report necessary and relevant information. Epilepsy affects each patient in a unique way, and patients differ in their capacity to understand various aspects of the disorder. As a result, clinicians must tailor discussions to clarify the impact of the condition on the specific patient's quality of life and expectations of the treatment plan. These discussions will improve the likelihood that the patient will comply with the plan of treatment.

The clinician should impress upon the patient, family, and patient's friends the critical need to follow the prescribed drug regimen. Nonadherence to ASM treatment regimen is associated with increased risk of mortality, as well as hospitalization and injury [58]. (See "Comorbidities and complications of epilepsy in adults".)

Written instructions on how and when to take the drugs should be provided and should explain the dosing regimen and any potential adverse effects (table 5 and table 6). The patient must also be warned not to stop taking an ASM and not to allow a prescription to run out or expire.

Patients should be urged not to start any other prescription, over-the-counter medications, dietary supplements, or herbal remedies without first contacting their clinician because these might affect serum concentrations of their ASMs [59,60]. (See "Initial treatment of epilepsy in adults", section on 'Pharmacokinetics'.)

Seizure calendar — Patients and family members should be asked to record seizures and ASM doses on a calendar or diary, which can then be brought or sent to the clinician for review. Seizure triggers should be indicated. The patient and family should note on the calendar the hour at which any symptoms occur. Electronic seizure diaries are also available [61,62].

The seizure calendar helps to monitor and encourage compliance. The seizure calendar also may be used to track the patient's response to drug therapy, including possible side effects. Seizure calendars can help identify seizure triggers. In one study of 71 patients completing daily seizure diaries, both lack of sleep and higher self-reported stress and anxiety were associated with seizure occurrence [63]. Seizures were also associated with the patients' own prediction of the likelihood of seizure occurrence. Other reported seizure triggers include visual, olfactory, and auditory stimuli; alcohol consumption; missed meals; and hormone fluctuations related to the menstrual cycle [64]. (See "Initial treatment of epilepsy in adults", section on 'Catamenial epilepsy'.)

Clinicians should recognize that patients are often unaware of their seizures and may therefore significantly underestimate the number of seizures that occur, especially those that occur during sleep or that disrupt consciousness [65]. Prolonged electroencephalography (EEG) recordings may be helpful in such patients to determine seizure frequency, either ambulatory or in a video-EEG monitoring unit. (See "Video and ambulatory EEG monitoring in the diagnosis of seizures and epilepsy".)

Generic substitution — The use of generic versus brand-name ASMs in people with epilepsy has attracted much attention and debate, and the evidence is mixed in terms of whether generic substitution of ASMs has an adverse impact on seizure control and toxicity.

Using pharmacokinetic data submitted to the FDA, one study found that while most generic ASMs provide total drug delivery similar to the reference product, differences in peak concentrations were more common, and switches between generic products caused greater changes in plasma drug concentrations than generic substitution of the reference product [66]. It is possible that the small, FDA-allowed variations in pharmacokinetics between a name brand and its generic equivalent (and between generic equivalents) can lead to either toxicity or seizures in some patients who, for unknown reasons, are particularly vulnerable [67-71]. At least for generic lamotrigine, however, such variations do not appear to cause harm [72-74].

Examples of published reports with indirect evidence that generic substitution is a potential problem include:

Three large case-control studies have found that changes in ASM formulation involving generics was a risk factor for emergency or hospital-level treatment of epilepsy (odds ratio [OR] 1.78 to 1.81) [75-77].

Some, but not all [78,79], studies using medical and pharmacy claims databases have found that generic switching of ASMs is associated with higher epilepsy-related medical utilization rates (eg, hospitalizations) and seizure-related injuries [80-84].

A retrospective study of breakthrough seizures that occurred in association with generic substitution found that ASM blood levels at the time of the seizure were on average 33 percent lower than previous levels obtained when the patient was using brand-name ASMs [85].

Additional anecdotal reports, small case series, and patient surveys [86-89].

By contrast, a systematic review and meta-analysis of seven trials in which the frequency of seizures was compared between a brand-name ASM and a generic alternative found no difference in the odds of seizures between treatment regimens [90]. The FDA maintains that there is no convincing evidence that people with epilepsy have lessened seizure control when taking generic medications. In addition, an analysis of generic oral ASMs approved in Europe concluded that the risk of non-bioequivalence between individual generic products was small and that switching across generic products was unlikely to cause clinically important changes in plasma drug levels [91].

Patients should be aware that pharmacists or mail-order pharmacies sometimes make generic substitutions at the point of sale, and that they should check with their clinician prior to accepting this substitution. Additional clinical and laboratory monitoring with plasma drug levels may be advisable with changes in drug formulation. Clinicians should consider the possibility of change in drug formulation as a cause of unexpected breakthrough seizures or toxicity along with other possible explanations, including differences in pharmacokinetics or appearance, which can influence adherence.

Alcohol intake — Alcohol consumption in small amounts (one to two drinks per day) may not affect seizure frequency or serum levels of ASMs in patients with well-controlled epilepsy [92]. Heavier alcohol intake (three or more drinks per day) increases the risk of seizures, particularly during the withdrawal period (7 to 48 hours after the last drink), and this practice should be strongly discouraged [93].

In an effort to enable people with epilepsy to live as normal a life as possible, it may be reasonable to advise that limited alcohol intake is acceptable, provided there is no history of alcohol or substance abuse or a history of alcohol-related seizures. However, patients should be aware that the data are not definitive at this time. Patients who are otherwise medically cleared to drive should nevertheless avoid driving and other high-risk activities for 24 to 48 hours after heavy alcohol intake due to the higher risk of seizures.

Nonadherence with antiseizure medication therapy — Up to 50 percent of patients with epilepsy may not take their medications as directed; over one-half of those evaluated in emergency departments for recurrent seizures have been nonadherent [94]. Nonadherence to ASM treatment regimen is not only associated with increased seizures, but also with increased risk of mortality, as well as hospitalization and injury [58,95].

Clinicians should suspect nonadherence if a patient denies the diagnosis of epilepsy, has limited financial means to pay for ASMs, has difficulty tolerating side effects, or forgets when or how to take medication because of memory impairment. An unexpected increase in the number or severity of seizures, or either subtherapeutic or supratherapeutic serum drug concentrations, also suggests nonadherence. However, serum levels can fluctuate due to a number of factors; thus, they should be interpreted with some caution.

Adherence diminishes when intervals between office visits grow longer and when medication regimens grow increasingly complex and expensive. Clinicians should be attuned to out-of-pocket costs and strive to use the simplest regimen possible, with generic substitutions when appropriate. (See 'Generic substitution' above and "Patient education: Coping with high prescription drug prices in the United States (Beyond the Basics)".)

Nonadherence also often results from a failure to effectively communicate. Written information about medications and changes in dosing should be provided in simple language. Improving the patient's understanding of their disorder and the need for regular intake of medications may also improve motivation and adherence. One randomized study showed that at least short-term compliance was improved with an intervention that linked intake of medication with a particular time, place, or activity [96]. Another found that three sessions of motivational interviewing and behavior-change techniques improved not only medication adherence but also self-perceptions of control and coping [97].

DRUG-RESISTANT EPILEPSY — There is no standardized definition of drug-resistant epilepsy, previously referred to as medically intractable epilepsy. A task force of the International League Against Epilepsy proposed that drug-resistant epilepsy may be defined as failure of adequate trials of two tolerated and appropriately chosen and used antiseizure medication (ASM) schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom [98]. (See "Evaluation and management of drug-resistant epilepsy", section on 'Definition'.)

The diagnosis and classification of epilepsy should be reconsidered in patients whose seizures do not respond to ASM trials. In particular, video-electroencephalography (EEG) monitoring to confirm the epileptic nature of spells should be considered in anyone still having seizures after two ASM trials or more than one year of treatment. (See "Video and ambulatory EEG monitoring in the diagnosis of seizures and epilepsy".)

Established treatment options for medically refractory epilepsy in adults include epilepsy surgery and vagus nerve stimulation (see "Surgical treatment of epilepsy in adults" and "Vagus nerve stimulation therapy for the treatment of epilepsy"). Deep brain stimulation and responsive cortical stimulation are emerging valid treatment options for select patients with drug-resistant epilepsy (see "Evaluation and management of drug-resistant epilepsy", section on 'Deep brain stimulation' and "Evaluation and management of drug-resistant epilepsy", section on 'Responsive cortical stimulation'). The ketogenic or modified Atkins diet may be helpful in selected patients. (See "Surgical treatment of epilepsy in adults" and "Ketogenic dietary therapies for the treatment of epilepsy" and "Vagus nerve stimulation therapy for the treatment of epilepsy".)

One published guideline suggests that patients whose seizures are uncontrolled after 12 months should be referred to a specialized epilepsy center when possible [99].

The evaluation and management of patients with medically refractory epilepsy is discussed separately. (See "Evaluation and management of drug-resistant epilepsy".)

ALTERNATIVE THERAPIES — Several randomized trials have demonstrated modest efficacy of a standardized preparation of cannabidiol oil in specific patient groups (eg, Dravet syndrome, Lennox-Gastaut syndrome). However, unregulated formulations containing lower concentrations of CBD have only anecdotal evidence in support of their efficacy. The randomized trial data are reviewed separately. (See "Evaluation and management of drug-resistant epilepsy", section on 'Cannabinoids' and "Seizures and epilepsy in children: Refractory seizures", section on 'Cannabinoids' and "Dravet syndrome: Management and prognosis" and "Epilepsy syndromes in children", section on 'Lennox-Gastaut syndrome'.)

Some other herbal medicines and dietary supplements, including melatonin, may have anticonvulsant effects, but few have been tested in rigorous trials [100-102]. Other herbal medicines and dietary supplements may instead be proconvulsant [103]. In addition, as with other drugs, alternative medications and supplements can affect the metabolism of antiseizure medications (ASMs) and can thus alter drug levels. In addition, patients should be asked about their use of alternative medications and supplements, and consideration should be given to additional monitoring of ASM levels in such patients.

In one trial, acupuncture therapy was compared with a sham procedure in 34 patients with epilepsy and found no benefit for seizure frequency, seizure-free weeks, or quality of life [104,105].

SPECIAL POPULATIONS

Women of childbearing age — A number of issues are important in women of childbearing age, especially if they are considering becoming or are already pregnant [106-109]. Clinicians should regularly review these issues with their female patients with epilepsy [3]. Pregnancies should be planned, and women with epilepsy require close follow-up in pregnancy. (See "Management of epilepsy during preconception, pregnancy, and the postpartum period".)

Effect of antiseizure medications on the fetus — There is an increased risk of both major and minor malformations in fetuses exposed to antiseizure medications (ASMs). In addition, there is accumulating evidence from observational studies that anticonvulsant therapy during pregnancy may have deleterious effects on cognitive and developmental outcomes of exposed children later in life. (See "Risks associated with epilepsy during pregnancy and the postpartum period", section on 'Effects of ASMs on the fetus and child'.)

ASM therapy should be optimized before conception, if possible, to minimize exposure of the fetus to potential teratogenic effects of ASMs. Because there is no agreement as to which ASM is least teratogenic, the ASM that stops seizures in an individual patient is the one that should be used. An exception is valproate, for which there are strong data regarding increased risk of malformations and adverse developmental outcomes. Where possible, valproate should be avoided in women of childbearing potential and should not be prescribed as first-line therapy for focal epilepsy in these patients, given the availability of numerous other ASMs with similar efficacy and lower fetal risks [110]. For seizure or epilepsy types where valproate is the most effective treatment (eg, some genetic generalized epilepsies), a process of shared decision making is particularly important when choosing first-line therapy, accounting for the fetal risks associated with valproate as well as the risks and benefits of alternative therapies. (See "Management of epilepsy during preconception, pregnancy, and the postpartum period", section on 'Choice of antiseizure medication'.)

Folic acid supplementation — Folate should be routinely prescribed to all women of childbearing age taking ASMs. Patients taking valproate or carbamazepine should receive daily folic acid supplementation (up to 4 mg/day) for one to three months prior to conception. Women who are taking other ASMs should take the more standard lower dose of folic acid (0.4 to 0.8 mg/day). (See "Management of epilepsy during preconception, pregnancy, and the postpartum period", section on 'Folic acid supplementation'.)

Contraception — Enzyme-inducing ASMs lower the efficacy of hormonal contraceptives (eg, oral contraceptive pills, vaginal ring, etonogestrel implant). Thus, for patients taking enzyme-inducing ASMs, long-acting reversible contraceptive (LARC) choices of intrauterine devices or intramuscular depot medroxyprogesterone acetate are suggested. Alternatively, a higher-dose combined oral contraceptive pill may be effective if one of the LARC options is not used, although precise studies are lacking. This issue is discussed in greater detail separately. (See "Management of epilepsy during preconception, pregnancy, and the postpartum period", section on 'Birth control'.)

Fertility — While a number of studies have suggested that women with epilepsy have increased rates of infertility, as high as 33 to 38 percent [111,112], other studies have not confirmed this finding [113]. It is also uncertain whether this association is linked to epilepsy itself or to ASM treatment.

Potential confounding factors in assessing a possible association include lower marriage rates and a lower rate of planned pregnancies. The latter may result because the woman may be concerned about teratogenicity, her ability to care for a child, and increased risk of epilepsy in her child [114].

There is evidence that suggests that ASM use may affect fertility. In a prospective cohort study of 375 women with epilepsy, infertility was linked to polytherapy, as well as to older age, and lower education [111]. Valproate, in particular, has been linked to an increased risk of polycystic ovary disease, a leading cause of infertility in woman [115]. (See "Epidemiology, phenotype, and genetics of the polycystic ovary syndrome in adults", section on 'High-risk groups'.)

Poststroke seizures — Stroke is the most common cause of seizures and epilepsy in population studies of adults over the age of 35 [116]. A 2020 systematic review and meta-analysis of seizures occurring after acute ischemic stroke reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy) included 25 studies with 13,573 patients [117]. The pooled incidence of poststroke seizures was 5.9 percent. Among studies reporting the time of seizure onset, the incidence of early poststroke seizures (occurring within seven days) was 3.2 percent, while the incidence of late poststroke seizures (occurring after seven days) was 6.7 percent. In an international, multicenter prospective study from 2000, poststroke seizures occurred in 168 of 1897 patients (8.9 percent) after hemispheric stroke, including 140 of 1632 (8.6 percent) with ischemic stroke and 28 of 265 (10.6 percent) with hemorrhagic stroke [118]. However, recurrent seizures were rare during the nine months of follow-up, occurring in only 2.5 percent of patients.

Seizures occurred within 24 hours of the stroke in 43 percent of patients in the international prospective study [118]. The pathogenesis of these early-onset seizures may be related to local ion shifts and release of high levels of excitotoxic neurotransmitters in the area of ischemic injury [119].

By contrast, an underlying permanent lesion that leads to persistent changes in neuronal excitability appears to be responsible for late-onset seizures after stroke and other brain injuries, and probably accounts for the fact that the risk of chronic epilepsy is higher in patients with late rather than early occurrence of seizures. In one study, for example, 118 patients who had a thrombotic stroke had a bimodal distribution of seizures either within two weeks or from 6 to 12 months after the stroke [120]. Epilepsy developed in more patients with late than early seizures (90 and 35 percent, respectively).

The risk of late-onset seizures may increase over time. In a population-based study of over 3000 patients presenting with first stroke, poststroke epilepsy (defined as ≥2 unprovoked seizures occurring after the acute phase of stroke) developed in 213 patients (6.4 percent) after a mean follow-up of four years [121]. The estimated cumulative incidence of epilepsy rose from 3.5 percent at one year, which is similar to estimates from prior studies with shorter-term follow-up, to over 12 percent at 10 years.

The most consistently identified risk factors for acute and late poststroke seizures are worse stroke severity, cortical location, and hemorrhagic lesions [118,121-125]. For primary intracerebral hemorrhage, subcortical hematoma location may actually pose higher risk for late seizures than cortical location [126]. Younger age has been reported as a risk factor for late seizures in at least one large study [121]. One prospective study found that preexisting dementia was a risk factor for late seizures (odds ratio [OR] 4.66, CI 1.34-16.21) but not for early seizures [127]. Dementia is a risk factor for epilepsy in patients without stroke as well. (See "Seizures and epilepsy in older adults: Etiology, clinical presentation, and diagnosis".)

Most seizures following stroke are focal at onset, but secondary generalization is common, particularly in patients with late-onset seizures. Status epilepticus is relatively uncommon, occurring in 9 percent of 180 patients with poststroke seizures in one report [128].

When to treat — Given the relatively low frequency of recurrent seizures after stroke, and an absence of absolute predictors of poststroke epilepsy, the decision of when to treat patients for a poststroke seizure is difficult. Nevertheless, most clinicians empirically treat patients who develop late-onset seizures in the setting of a stroke history within the previous two to three years [119].

The efficacy of specific ASMs for poststroke seizures has not been rigorously assessed in controlled trials, although most seizures can be controlled with a single agent [129]. The evidence does not support one specific ASM over another [130]. Several considerations factor into the choice of ASM in this population. Studies suggest that newer ASMs have similar efficacy but a more favorable adverse event profile in older patients (see "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects" and "Seizures and epilepsy in older adults: Treatment and prognosis"). In one prospective randomized trial, the lamotrigine treatment arm had fewer dropouts due to adverse events than did the carbamazepine arm; lamotrigine was also more efficacious, although this did not reach statistical significance [131]. Gabapentin has been associated with 80 percent seizure remission in one uncontrolled study of poststroke epilepsy [132].

Older patients — ASM use in older adult patients is complicated by several factors, including age-related alterations in protein binding, reduced hepatic metabolism, and diminished renal clearance of medications. In addition, medical comorbidities and polypharmacy are more often a concern in older adults. The selection of ASM treatment in older adults is discussed separately. (See "Seizures and epilepsy in older adults: Treatment and prognosis".)

Sleep-related epilepsy — Several epilepsy syndromes manifest with seizures that occur exclusively or predominantly during sleep. Most are focal epilepsy syndromes with genetic or structural etiologies. The most common of these is nocturnal frontal lobe epilepsy (NFLE), also referred to as "sleep-related hypermotor epilepsy." Nocturnal temporal, parietal, and occipital lobe epilepsies also occur but are less common and have overlapping clinical features with NFLE. Most have an onset in adolescence or early adulthood. The clinical features, diagnosis, differential diagnosis, and management of sleep-related epilepsy are discussed separately. (See "Sleep-related epilepsy syndromes", section on 'Sleep-related focal epilepsies'.)

Other causes — The treatment of epilepsy in the setting of brain tumors and head trauma is discussed separately. (See "Seizures in patients with primary and metastatic brain tumors" and "Posttraumatic seizures and epilepsy".)

COMPLICATIONS AND COMORBIDITIES — Epilepsy is a chronic disease associated with an increased risk of a variety of psychiatric and medical comorbidities that can adversely impact quality of life as well as life expectancy. Comorbidities can arise due to common underlying predispositions, direct effects of seizures, underlying epilepsy etiologies, and adverse effects of antiseizure medications (ASMs) and other therapies. Depression and anxiety are particularly common in adults with epilepsy, and screening should be a routine part of long-term follow-up.

These and other comorbidities and complications of epilepsy in adults are discussed separately. (See "Comorbidities and complications of epilepsy in adults".)

DISCONTINUING ANTISEIZURE MEDICATION THERAPY — After a two- to four-year seizure-free interval, it is reasonable to begin a discussion about continued antiseizure medication (ASM) therapy versus a trial of discontinuation. This decision must be individualized and weighs the risks of seizure recurrence against the possible benefits of drug withdrawal, all of which may vary significantly across patients.

Risks and benefits of drug withdrawal — There are several reasons to consider discontinuing ASMs in appropriate patients.

It offers patients a sense of being "cured," whereas the need for chronic medication confers a perception of continuing disability.

No drug is entirely benign, and adverse effects associated with chronic therapy may take years to become evident.

Cognitive and behavioral side effects of ASMs may be subtle and not fully recognized until drugs are discontinued [133].

Some ASMs are expensive and pose a significant financial burden for many patients.

There may be special circumstances, such as pregnancy or serious coexisting medical conditions, in which outcomes may be improved and management simplified in the absence of unnecessary ASM therapy.

The main disadvantage is the possibility that seizures will recur. The psychosocial implications may be particularly significant for adults who are employed, who drive, and whose lifestyle would be adversely affected by recurrent seizures. There is also a potential risk that seizure control will not be regained to the same degree when therapy is resumed compared with before discontinuation. The risk of this scenario appears to be small, however [134,135].

Estimating risk of seizure recurrence — There is no certain way to prospectively identify patients who will remain seizure free after they discontinue ASM therapy and no high-quality studies to guide decision making. In addition to confirming the time elapsed since the last seizure, clinicians should review the epilepsy history and most recent neuroimaging studies. An electroencephalogram (EEG) is often obtained to help with risk stratification, as epileptiform abnormalities are a risk factor for seizure recurrence [134]. However, their contribution appears to be quite modest beyond what is derived from other clinical factors, and we do not routinely obtain an EEG in all patients who are considering drug discontinuation.

Based on a meta-analysis of observational studies with varying entry criteria and patient characteristics at the time of drug discontinuation in nearly 10,000 patients, the cumulative seizure recurrence rate after drug withdrawal in patients with epilepsy is approximately 35 percent [136]. In nonsurgical cohorts, approximately two-thirds of recurrences occur within the first year after drug discontinuation; in surgical cohorts, only half of eventual recurrences occur within the first year. (See "Surgical treatment of epilepsy in adults", section on 'Antiseizure medication management after surgery'.)

Prospective studies comparing continued ASM treatment with drug withdrawal reported the following results:

The first study included 1013 patients with epilepsy who had been seizure free for at least two years (range two to six years); these patients were randomly assigned to either continued ASM treatment or slow withdrawal [137]. By two years after randomization, 22 and 41 percent of patients, respectively, experienced seizure relapse. The most important factors predicting outcome were longer seizure-free periods before attempting drug withdrawal (which reduced seizure recurrence) and a history of tonic-clonic seizures treated with more than one ASM (which increased recurrence).

The second study included 330 patients with epilepsy who were also seizure free for two years on a single ASM and had consented to drug withdrawal [138]. Approximately two-thirds of the patients elected to proceed with drug withdrawal, and the remaining one-third continued therapy. The overall rate of seizure relapse was higher among those who discontinued therapy (50 versus 28 percent). Among those who discontinued therapy, the probabilities of relapse at one, two, three, and five years were 26, 43, 49, and 52 percent, respectively. Duration of active disease and length of remission before ASM withdrawal influenced the risk of relapse.

A third study enrolled patients who were seizure-free on ASM monotherapy and randomly assigned them to ASM withdrawal (n = 79) or no withdrawal (n = 81) [133]. At 12 months, there was a trend toward a higher seizure relapse rate in the withdrawal group (15 percent versus 7 percent, RR 2.46, 95% CI 0.85-7.08). While the difference was not statistically significant, this may be due to the small number of participants, leading to wide confidence intervals around the estimate of effect.

More than 20 different variables have been associated with risk of seizure recurrence upon ASM discontinuation in individual studies [136]. In a meta-analysis of individual patient data from 10 studies and 1769 patients examining risk of seizure recurrence after drug discontinuation, the following factors were independent predictors of seizure recurrence [134]:

Epilepsy duration before remission (longer duration associated with higher risk)

Seizure-free interval before ASM withdrawal (shorter interval associated with higher risk)

Age at onset of epilepsy (onset in adulthood associated with higher risk)

History of febrile seizures

Number of seizures before remission (≥10 associated with higher risk)

Absence of a self-limiting epilepsy syndrome (eg, absence epilepsy, benign epilepsy with centrotemporal spikes)

Epileptiform abnormality on EEG before withdrawal

The magnitude of risk for any one of these variables ranged from 1.3 to 1.5 times the risk of recurrence compared with the absence of the variable. A history of seizure recurrence with past attempts at drug withdrawal was not an independent predictor of future failure.

A nomogram for individualized prediction of recurrence risk derived from the patient-level data in this meta-analysis is available at http://epilepsypredictiontools.info [134]. The nomogram should not be used as a substitute for an individualized discussion of a full range of potential risks and benefits. It does not apply to patients with acute symptomatic seizures or neonatal seizures, as these populations were not included in the study, or to patients with juvenile myoclonic epilepsy, who were underrepresented and who are known to have a high rate of seizure relapse (>80 percent) with attempted ASM withdrawal. Patients who have had epilepsy surgery were also underrepresented in the study. (See "Juvenile myoclonic epilepsy", section on 'Prognosis'.)

Other factors that may increase risk but for which the data are less consistent include [133,139-144]:

Identifiable brain disease (eg, brain tumor, congenital malformation, encephalomalacia)

Intellectual disability

Abnormal neurologic examination

Multiple seizure types

Poor initial response to treatment

Combination therapy at the time of withdrawal

Family history of epilepsy

Hippocampal atrophy or abnormal hippocampal signal on magnetic resonance imaging (MRI)

Thus, the choice to taper ASMs must be made on an individual basis, weighing the potential risk of seizure recurrence after discontinuing therapy against that of continuing therapy. The approach should be neither dogmatic nor inflexible. Each patient should have a reasonable understanding of the possible risks and benefits related to discontinuing drugs that are relevant to their own case. As an example, one may have quite different recommendations regarding ASM withdrawal in a 25-year-old woman who wishes to become pregnant than in a 25-year-old man whose livelihood depends on driving.

Even patients who are seizure free for several years and have none of the risk factors listed above still have approximately a 20 to 25 percent risk of seizure recurrence after ASM withdrawal, a much higher risk of seizures than the general population.

Because this risk cannot be known exactly for any given patient, and as the timing of a seizure recurrence cannot be predicted, many patients elect to continue ASM therapy rather than risk having seizures recur. However, one should also keep in mind that the risk is not zero even with continued ASMs.

Recommendations of others — A 2021 practice advisory from the American Academy of Neurology (AAN) for ASM withdrawal in seizure-free patients recommended that the decision should incorporate individual patient characteristics and preferences [145]. The AAN concluded that it is unknown if EEG or imaging studies inform the decision to withdraw ASMs. Based upon low-quality evidence, the AAN found no difference in quality of life for patients with well-controlled epilepsy who stop ASMs compared with those who continue taking ASMs. In addition, the evidence review did not suggest an increased risk of status epilepticus or death after ASM withdrawal.

Withdrawal schedule — There are no data that indicate an optimal tapering regimen when the decision is made to discontinue ASM therapy [146]. The following considerations may be helpful:

Rapid changes in drug treatment increase the risk of more severe seizures [147]. Slow rates of ASM taper (six months) were relatively similar to more moderate rates (two to three months) in one large study [137].

Exceptions are benzodiazepines and barbiturates, which should be discontinued very gradually to avoid withdrawal seizures.

Taper one drug at a time in patients on combination therapy.

There are no guidelines or general consensus regarding driving restrictions during and after ASM withdrawal. (See "Driving restrictions for patients with seizures and epilepsy", section on 'Discontinuing medication'.)

DRIVING AND OTHER RESTRICTIONS — States vary widely in driver licensing requirements for patients with epilepsy. The most common requirements are that patients be free of seizures for a specified period of time and that they submit a clinician's evaluation of their ability to drive safely.

Clinicians should also consider the potential neurotoxic side effects of antiseizure medications (ASMs), such as sedation and double vision (table 5) when counseling patients about driving.

A listing of individual state driving requirements can be found on the Epilepsy Foundation website at https://www.epilepsy.com/driving-laws. Additional details about driving restrictions in patients with epilepsy are discussed separately. (See "Driving restrictions for patients with seizures and epilepsy".)

Questions may arise about participation in sports and other activities, and clinicians may be asked to provide medical clearance before a patient can participate. These decisions should be individualized, weighing not only the potential risks of participation but also the benefits of physical exercise and social engagement [148].

Factors to consider include the type of sport or activity, the probability of a seizure occurring during the activity and related implications, the amount of supervision available during the activity, the patient's seizure type and severity, the consistency of any prodromal symptoms, relevant seizure precipitants, a history of seizure-related accidents or injuries, recent seizure control, degree of adherence to therapy, and the willingness of the patient and parents to take on risk. The International League Against Epilepsy has published a consensus-based guideline on sports participation in patients with epilepsy, which divides sports into three risk categories and proposes a decision-making framework for each risk category [148].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Seizures and epilepsy in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Seizures (The Basics)" and "Patient education: Epilepsy in adults (The Basics)" and "Patient education: Epilepsy and pregnancy (The Basics)")

Beyond the Basics topic (see "Patient education: Seizures in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Goals – The management of patients with epilepsy is focused on three main goals: controlling seizures, avoiding treatment side effects, and maintaining or restoring quality of life. (See 'Introduction' above.)

Need for ASM – Immediate antiseizure medication (ASM) therapy is usually not necessary in individuals after a single seizure and is typically reserved for individuals who are at high risk of recurrent seizures or those who have had two or more unprovoked seizures. (See "Initial treatment of epilepsy in adults", section on 'When to start antiseizure medication therapy'.)

We recommend initiating an ASM in monotherapy in individuals who are at high risk of recurrent seizures (Grade 1A). Selection of an ASM is individualized based upon the seizure type; potential adverse effects; interactions with other medications; comorbid medical conditions; age and gender, including childbearing plans; lifestyle and patient preferences; and cost. (See "Initial treatment of epilepsy in adults", section on 'Selection of an antiseizure medication'.)

If the first ASM trial is unsuccessful, a second ASM trial is recommended (Grade 1A). ASM therapy is as likely to fail from adverse effects of medication as from lack of efficacy. The chance of successful ASM treatment diminishes if the preceding ASM trial failure was due to lack of efficacy. However, treatment failure caused by adverse effects does not diminish the likelihood of success with subsequent ASM treatments. (See 'Subsequent drug trials' above.)

Measures to improve outcome – Regular outpatient office visits that include patient education, review of adverse medication effects, seizure calendar, and drug monitoring are suggested to improve compliance and the likelihood of a successful outcome. (See 'Maximizing the likelihood of a successful outcome' above.)

Women and ASMs – Women of childbearing age should be counseled regarding possible teratogenic effects of ASMs and should consider taking supplemental folate to limit the risk. Enzyme-inducing ASMs can limit the effectiveness of oral contraception; alternative forms of birth control should be considered in women taking these ASMs. (See 'Women of childbearing age' above.)

Specific adverse reactions of ASMs – Mood problems, anxiety, and depression are more prevalent in persons with epilepsy than in the general population. In addition, ASM treatment has been associated with suicidality. Patients treated with ASMs should be monitored for changes in mood and suicidality. (See 'Specific adverse reactions' above.)

Comorbidities and complications – Patients with epilepsy have a higher-than-expected risk of mortality (including sudden death), injury, and motor vehicle accidents. Seizure frequency is a major risk factor for these complications. It is reasonable to counsel patients regarding these risks when discussing compliance issues or aggressive treatment for medically refractory epilepsy. (See "Comorbidities and complications of epilepsy in adults".)

Driving restrictions – Individuals who have had a recent epileptic seizure may be restricted from driving. Patients who are experiencing substantial neurotoxic side effects from ASMs should also be counseled about their appropriateness for driving until such side effects abate. (See 'Driving and other restrictions' above.)

ASM discontinuation – Stopping ASMs can be considered in patients who have been seizure free for more than two years. Such decisions are individualized based on an evaluation of the individual's risk of seizure recurrence, adverse effects of ASM treatment, and the medical and psychosocial consequences of a recurrent seizure. ASM withdrawal should be slow, over a few to many months. (See 'Discontinuing antiseizure medication therapy' above.)

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Topic 2220 Version 68.0

References

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