Clinical Practice. 7(2):157–162, April 2017.
survey in the United States. Mov Disord. 2011;26(1):114–20.
Gamaldo CE, Earley CJ. Restless legs syndrome: a clinical update. Chest. 2006;130:1596.
and Periodic Limb Movement Disorder in Adults—An Update for 2012: Practice Parameters with an
Evidence-Based Systematic Review and Meta-Analyses.” Sleep. 2012;35(8):1037.
The Atlas Task Force. Recording and scoring leg movements. Sleep. 1993;16:748.
Avidan AY. Parasomnias and movement disorders of sleep. Semin Neurol. 2009;29:372.
continuous positive airway pressure. Sleep. 2003;26:717.
Syndrome Study Group. Sleep Med. 2013;14(7):675–684.
the European Sleep Research Society. Eur J Neurol. 2012;19(11):1385–1396.
syndrome: results of a prospective multicenter study. J Neurol. 2010;257:230.
conference at the Max Planck Institute. Sleep Med. 2007;8:520.
clinical practice. Mov Disord. 2008;23:2267.
prevalence of essential tremor. Mov Disord. 2010;25:534.
Deuschl G et al. Consensus statement of the movement disorder society on tremor. Ad Hoc Scientific
Committee. Mov Disord. 1998;13(Suppl 3):2.
Hedera P et al. Pharmacotherapy of Essential Tremor. J Cent Nerv Syst Dis. 2013;5:43–55.
Deuschl G et al. Treatment of patients with essential tremor. Lancet Neurol. 2011;10:148.
Standards subcommittee of the American Academy of Neurology. Neurology. 2011;77(19):1752–1755.
Subcommittee of the American Academy of Neurology. Neurology. 2005;5(64):2008.
Epilepsy is a disorder characterized by spontaneously recurring seizures.
Seizures can arise from a focal area of the brain (focal or partial
seizures) or arise diffusely from both brain hemispheres (primary
The optimal choice of antiepileptic drug (AED) treatment is based on
patient-specific considerations including seizure type (or epilepsy
syndrome, if defined), age, sex, concomitant medical conditions and
therapies, and AED adverse effects. Monotherapy is preferred;
polytherapy should be considered for patients with multiple seizure types
and/or when monotherapy (with 2 or 3 agents) fails at maximal tolerated
Standard AEDs, such as carbamazepine, phenytoin, and valproate, are
used commonly for patients with newly diagnosed epilepsy. Newer
AEDs (e.g., lacosamide, lamotrigine, levetiracetam, oxcarbazepine,
pregabalin, topiramate, zonisamide, ezogabine, perampanel,
eslicarbazepine) are often initially approved for add-on therapy in
patients with partial-onset seizures who do not respond to other AEDs.
Lamotrigine, oxcarbazepine, topiramate, lacosamide, and felbamate are
Enzyme-inducing AEDs (carbamazepine, phenobarbital, phenytoin)
increase the metabolism of many other drugs (e.g., warfarin,
contraceptive hormones). In addition, carbamazepine induces its own
metabolism and levels may decline during the first month of therapy
Serious idiosyncratic adverse effects have been associated with most
standard and new AEDs and include carbamazepine-associated
carbamazepine, phenobarbital, and phenytoin. The role of routine
laboratory monitoring for detection of these adverse effects is
controversial. Patients should know the signs or symptoms that should
prompt them to seek medical attention.
Unlike other AEDs, phenytoin displays capacity-limited
pharmacokinetics at serum concentrations that are clinically useful for
epilepsy treatment. As a consequence, phenytoin blood levels often
change disproportionately to changes in dosage, and time to steady state
varies significantly in individual patients based on the phenytoin
Serum concentration monitoring can be useful for selected AEDs when
there is a good correlation between concentration and therapeutic or
toxic responses. However, clinical criteria (seizure control, medication
tolerability) are the primary determinants of the need for dosage
The occurrence of seizure clusters (acute repetitive seizures) and status
epilepticus (prolonged or repeated seizures without recovery of
consciousness) warrants emergent AED therapy. Acute repetitive
seizures are often treated by parents or caregivers with rectal
diazepam. Status epilepticus is a life-threatening emergency and should
be treated with intravenous (IV) lorazepam as initial therapy.
Incidence, Prevalence, and Epidemiology
Approximately 10% of the population will experience a seizure at some time in their
life. Up to 30% of all seizures are provoked by central nervous system (CNS)
disorders or insults (e.g., meningitis, trauma, tumors, and exposure to toxins); these
seizures may become recurrent and require chronic treatment with AEDs. Reversible
conditions such as alcohol withdrawal, fever, and metabolic disturbances may
provoke acute, isolated seizures. These seizures, along with drug-induced seizures,
are not considered to be epilepsy and usually do not require long-termAED therapy.
Approximately 1% of the general population has epilepsy.
Terminology, Classification, and Diagnosis of Epilepsies
CLASSIFICATION OF SEIZURES AND EPILEPSIES
A seizure is the “transient occurrence of signs and/or symptoms due to abnormal
excessive or synchronous neuronal activity in the brain” (p. 471).
symptoms “may include alterations of consciousness, motor, sensory, autonomic, or
1 Epilepsy is a “disorder of the brain characterized by an
enduring predisposition to generate epileptic seizures and by the neurobiologic,
cognitive, psychological and social consequence of this condition” (p. 471).
definition, epilepsy requires the occurrence of two or more seizures that are not
acutely provoked by other illnesses or conditions.
3 Guidelines have recently been
updated to include a patient who has had one unprovoked seizure and has a high risk
(>60%) of a second seizure to be included in the definition of a person with
4 A commonly used classification scheme for epileptic seizures is shown in
5 Older terms such as “grand mal” and “petit mal” should not be used,
because their use may create confusion in the clinical setting. For example, it is
common for patients or caregivers to identify any seizure other than a generalized
tonic–clonic seizure as a “petit mal” seizure. This labeling may result in the selection
of an inappropriate medication.
Generalized tonic–clonic seizures are common. The patient loses consciousness
and falls at the onset. Simultaneously, tonic muscle spasms begin and may be
accompanied by a cry that results from air being forced through the larynx. Bilateral,
repetitive clonic movements follow. After the clonic phase, patients return to
consciousness but remain lethargic and may be confused for varying periods of time
(postictal state). Urinary incontinence and tongue biting is common. Primary
generalized tonic–clonic seizures affect both cerebral hemispheres from the outset.
Secondarily generalized tonic–clonic seizures begin as either simple or complex
partial seizures. The aura described by some patients before a generalized tonic–
clonic seizure represents an initial partial seizure that spreads to become a
secondarily generalized seizure. Identification of secondarily generalized tonic–
clonic seizures is important because some AEDs are more effective at controlling
primary generalized seizures than secondarily generalized seizures. In general,
partial seizures are often more difficult to control with AEDs as compared to primary
Absence seizures occur primarily in children and often remit during puberty;
affected patients may exhibit a second type of seizure. Absence seizures consist of a
brief loss of consciousness, usually lasting several seconds. Simple (typical) absence
seizures are not accompanied by motor symptoms; automatisms, muscle twitching,
myoclonic jerking, or autonomic manifestations may accompany atypical (complex)
absence seizures. Although consciousness is lost, muscle tone is maintained and
patients do not fall during absence seizures. Patients are unaware of their
surroundings and will have no recall of events during the seizure. Consciousness
returns immediately when the seizure ends, and postictal confusion does not occur.
Differentiation of atypical absence seizures from complex partial seizures may be
difficult if only a second-hand account of the episodes is available; identification of a
focal abnormality by an electroencephalogram (EEG) often is necessary to identify
complex partial seizures. This distinction is important for the proper selection of
Classification of Epileptic Seizures
Simple Partial Seizures (Without Impairment of Consciousness)
Specialsensory or somatosensory symptoms
Complex Partial Seizures (With Impairment of Consciousness; “dyscognitive features”)
Progressing to impairment of consciousness
With features as in simple partialseizures
With impaired consciousness at onset
With features as in simple partialseizures
Partial Seizures That Evolve to Generalized Seizures
Simple partialseizures evolving to generalized seizures
Complex partialseizures evolving to generalized seizures
Simple partialseizures evolving to complex partialseizures to generalized seizures
Generalized Seizures (Convulsive or Nonconvulsive)
Typicalseizures (impaired consciousness only)
Atonic (Astatic or Akinetic) Seizures
Unclassified Epileptic Seizures
classified in previously described categories
Simple partial (focal motor or sensory) seizures are localized in a single cerebral
hemisphere or portion of a hemisphere. Consciousness is not impaired during these
events. Various motor, sensory, or psychic manifestations may occur depending on
the area of the brain that is affected. A single part of the body may twitch, or the
patient may experience only an unusual sensory experience.
Complex partial seizures result from the spread of focal discharges to involve a
larger area. Consciousness is impaired and patients may exhibit complex but
inappropriate behavior (automatisms) such as lip smacking, picking at clothing, or
aimless wandering. A period of brief postictal lethargy or confusion is common.
In 2010, the International League Against Epilepsy recommended modifications to
the traditional seizure classification scheme and terminology. Whereas some of the
terminology remained unchanged, seizures limited to one hemisphere are now termed
“focal seizures” (instead of partial seizures) and the formal distinction between
complex partial and simple partial seizures is eliminated.
existing literature on epilepsy makes use of the traditional seizure terminology, we
have retained the use of “partial,” “complex partial,” and “simple partial” for this
Epilepsy can be classified based on seizure type as shown in Table 60-1. Epilepsy
syndromes can be defined on the basis of seizure type as well as cause (if known),
precipitating factors, age of onset, characteristic EEG patterns, severity, chronicity,
family history, and prognosis. Accurate diagnosis of epilepsy syndromes may better
guide clinicians regarding the need for drug therapy, the choice of appropriate
medication, and the likelihood of successful treatment.
have been defined; a complete listing is beyond the scope of this chapter. Several are
of interest with respect to pharmacotherapy and are described in Table 60-2.
Optimal treatment of seizure disorders requires accurate classification (diagnosis) of
seizure type and appropriate choice and use of medications. Seizure classification
may be straightforward if an adequate history and description of the clinical seizure
are available. Physicians often do not observe patients’ seizures; thus, family
members, teachers, nurses, and others who have frequent direct contact with patients
should learn to observe accurately and objectively describe and record these events.
The onset, duration, and characteristics of a seizure should be described as
completely as possible. Several aspects of the events surrounding a seizure may be
especially significant: the patient’s behavior before the seizure (e.g., Did the patient
complain of feeling ill or describe an unusual sensation?), deviation of the eyes or
head to one side or localization of convulsive activity to one portion of the body,
impaired consciousness, loss of continence, and the patient’s behavior after the
seizure (e.g., Was there any postictal confusion?). In addition, it is helpful if the
observer can record the length of the event and how long it took for the patient to
return to baseline. A video of the event could be especially helpful. The patient and
caregivers should have a seizure calendar or diary to record events. Many options
exist to track seizures including online sites and smart phone applications. Those
who observe a seizure should not try to label the seizure but should be encouraged to
describe the event fully and objectively.
Accurate seizure diagnosis and identification of the type of epilepsy or epilepsy
syndrome also depend on neurologic examination, medical history, and diagnostic
techniques, such as EEG, computed tomography (CT), and magnetic resonance
imaging (MRI). The EEG often is critical for identifying specific seizure types. CT
scanning may help assess newly diagnosed patients, but MRI is preferred. MRI may
locate brain lesions or anatomic defects that are missed by conventional radiographs
precede generalized tonic–clonic
Generalized seizures: atypical
pattern. Cognitive dysfunction
and mental retardation. Status
clusters of multiple seizures.
Tonic–clonic seizures in ˜40%.
and 8 years. Significant genetic
secondary generalized seizures
AED, antiepileptic drug; EEG, electroencephalogram; FDA, US Food and Drug Administration.
Early control of epileptic seizures is important because it allows normalization of
patients’ lives and prevents acute physical harm and long-term morbidity associated
with recurrent seizures. In addition, early control of tonic–clonic seizures is
associated with a reduced likelihood of seizure recurrence. Early control of epileptic
NONPHARMACOLOGIC TREATMENT OF EPILEPSY
Alternatives or adjuncts to pharmacotherapy may be helpful in some patients. Surgery
is an extremely effective treatment in selected patients. Depending on the epilepsy
syndrome and procedure performed, up to 90% of patients treated surgically may
improve or become seizure-free. A study of 80 patients with medically refractory
temporal lobe epilepsy randomly assigned to either surgery or continued medical
treatment showed that after 1 year patients were more likely to be seizure-free after
13 Surgery is advocated as early therapy for some patients with specific
epilepsy syndromes, such as mesial temporal sclerosis. Early surgical intervention
may prevent or lessen neurologic deterioration and developmental delay.
Dietary modification may be used for patients who cannot tolerate AEDs or to
treat seizures that are not completely responsive to AEDs. In most circumstances,
dietary modification consists of a ketogenic diet. This low-carbohydrate, high-fat diet
results in persistent ketosis, which is believed to play a major role in the therapeutic
effect. Ketogenic diets seem to be most beneficial in children; they are also used as
adjuncts to ongoing AED treatment.
The vagus nerve stimulator is an implantable device approved for treatment of
intractable partial seizures. This device uses electrodes attached around the left
branch of the vagus nerve. The electrodes are attached to a programmable stimulator
that delivers stimuli on a regular cycling basis; patients can also use “on demand”
stimulation at the onset of seizures by swiping the magnet over the subcutaneously
implanted stimulator. Approximately 30% to 40% of patients who are so treated have
a positive response (50% reduction in seizures).
16 The primary side effect of this
device is hoarseness during stimulation; infrequently, this is accompanied by left
Responsive neurostimulation is a newer non-pharmacologic option for treating
intractable partial-onset seizures. Its role in therapy is yet to be determined.
Avoidance of Potential Seizure Precipitants
It is impossible to generalize about environmental and lifestyle precipitants of
seizure activity in persons with epilepsy. Individual patients or caregivers may
identify specific circumstances such as stress, sleep deprivation, acute illness, or
ingestion of excessive amounts of caffeine or alcohol, which may increase the
likelihood of a recurrent seizure event. Some women experience an increase in the
frequency and/or severity of seizures around the time of menstruation or ovulation.
Patients with epilepsy should avoid activities that seem to precipitate seizures; as
always, the goal is complete seizure control with as little alteration in quality of life
Pharmacotherapy is the mainstay of treatment for epilepsy. Therefore, patient
education regarding medications and consultation among health care professionals
regarding the optimal use of AEDs are essential to quality patient care. Optimal AED
therapy completely controls seizures in approximately two-thirds of patients.
Optimization of drug therapy depends on several factors, with the choice of
appropriate AED, individualization of dosing, and adherence being the most
Many AEDs have a relatively narrow spectrum of efficacy against selected seizure
types; therefore, choice of appropriate drug therapy for a specific patient depends on
an accurate diagnosis of epilepsy. In addition, toxicity must be considered when
selecting an AED. Preferred drugs for specific types of seizures and common
epileptic syndromes are listed in Tables 60-2 and 60-3. Although certain drugs are
preferred, the identification of the most effective drug for a particular patient may be
a process of trial and error; several medication trials may be necessary before
success is achieved. It is important to keep in mind that certain AEDs can worsen
The consensus method was used to analyze expert opinion on treatment of three
epilepsy syndromes and status epilepticus.
20 The experts recommended monotherapy
first, followed by a second monotherapy agent if the first failed. If the second
monotherapy failed, the experts were not in agreement on whether to try a third
monotherapy agent or to combine two therapies. The experts recommended epilepsy
surgery evaluation after the third failed AED for patients with symptomatic
localization-related epilepsies.
To assess the evidence on efficacy, tolerability, and safety of many of the new
AEDs in treating children and adults with new-onset and refractory partial and
generalized epilepsies, a panel evaluated the available evidence.
that AED choice depends on seizure and syndrome type; patient age; concomitant
medications; and AED tolerability, safety, and efficacy. The results of these two
evidence-based assessments provide guidelines for the use of newer AEDs in
patients with new-onset and refractory epilepsy.
The individual patient’s response to AED treatment (i.e., seizure frequency and
severity, and symptoms of toxicity) must be the major focus for therapy assessment.
In general, the goal of AED treatment is administration of sufficient medication to
completely prevent seizures without producing significant toxicity.
this goal may be compromised for many patients; it may not be possible to
completely prevent seizures without producing intolerable adverse effects. Thus, the
therapeutic end points achieved can vary among patients; optimization of AED
therapy for a specific person depends on tailoring therapy to the patient’s needs and
lifestyle. It is rarely optimal to administer “standard” or “usual” doses of an AED to
a patient or to adjust doses to achieve a “therapeutic blood level” without
considering the effect of the dose or serum concentration on the patient’s condition
and quality of life. As with many conditions requiring chronic drug therapy, patient
participation in developing and evaluating a therapeutic plan is extremely important.
Patients should be educated regarding the expected positive and negative effects of
their AED therapy, and they must be encouraged to communicate with their health
care provider regarding their responses to prescribed AEDs.
Antiepileptic Drugs (AEDs) Useful for Various Seizure Types
Most Effective With Least Toxicity
Valproate Carbamazepine Carbamazepine Ethosuximide Valproate
Levetiracetam Oxcarbazepine Oxcarbazepine Valproate Clonazepam
Lamotrigine Levetiracetam Levetiracetam Lamotrigine Rufinamide
Levetiracetam Lamotrigine Lamotrigine
Levetiracetam Valproate Valproate Lamotrigine
Levetiracetam Gabapentin Gabapentin Clobazam (Lennox–
Eslicarbazepine Eslicarbazepine
Effective, but Often Poorly Tolerated or Cause Unacceptable Toxicity
Phenobarbital Phenobarbital Clorazepate Clonazepam (Felbamate)
Primidone Primidone Phenobarbital
may differ. The use of phenobarbital and primidone is discouraged.
before their roles as possible primary AEDs are clarified.
treatment options have been exhausted.
For selected AEDs, proper use and interpretation of serum concentrations are
important for optimizing treatment regimens in epilepsy.
clinical response to AED treatment must be the major focus for therapy assessment.
Individual patients often differ dramatically in their response to a particular serum
drug concentration; therefore, therapeutic serum concentrations should be considered
only as guidelines for treatment. Many patients’ condition may be controlled with
serum drug concentrations above or below the usual therapeutic range.
patients, dosage adjustment to get the patient “in range” is not warranted. It is better
to “treat the patient, not the level.”
Interestingly, a recent Cochrane Review found no evidence that measuring AED
concentrations routinely to inform dose adjustments is superior to dose adjustments
based on clinical information.
27 However, the authors do state that their review does
not exclude the possibility that AED serum concentration might be useful in special
situations or in selected patients.
Measurement of serum drug concentrations may provide clinically useful information
Uncontrolled seizures despite administration of greater-than-average doses: Serum
concentrations of AED may help distinguish drug resistance from subtherapeutic
drug concentrations caused by malabsorption, nonadherence, or rapid
Seizure recurrence in a patient whose seizures were previously controlled: This is
often owing to nonadherence with the prescribed medication regimen.
of the dose and serum concentration of the responsible drug is helpful.
Assessment of patient adherence: Although monitoring AED serum concentrations
can be used to assess patient adherence with therapy, conclusions must be based
on comparisons with previous steady state serum concentrations that reflected
reliable intake of a given dose of AED.
Documentation of desired results from a dose change or other therapeutic maneuver
(e.g., administration of a loading dose): When patients are receiving multiple
AEDs, it is often appropriate to measure serum concentrations of all drugs after a
change in the dose of one agent because changes to one drug frequently affect the
pharmacokinetic disposition of other drugs.
When precise dosage changes are required: On occasion, small changes in the dose
of a drug (e.g., phenytoin) can result in large changes in both the serum
concentration and clinical response. In addition, cautious titration of dosage and
serum concentration may be necessary to avoid intoxication. Knowledge of the
serum drug concentration before the dosage change may allow the clinician to
select a more appropriate new maintenance dose.
During pregnancy, AED serum concentrations often decline and dosage adjustments
may be warranted to maintain adequate seizure protection. Free (unbound)
concentrations should be monitored for highly protein-bound AEDs. AED serum
concentrations should be monitored after delivery, particularly when dosage
escalations have been made during pregnancy.
Frequent, “routine” determinations of serum AED concentrations are costly and not
warranted for patients whose clinical status is stable. Clinicians may tend to focus
attention on normal variability in serum concentrations rather than on the patient’s
clinical status; as a result, unnecessary dosage adjustments may be made to make
serum concentrations fit the “normal range.” A plan of action for what the clinician is
going to do with the information once it is obtained should be in place before
obtaining the sample. Therefore, the results of individual serum concentration
determinations must be evaluated carefully to decide whether a significant, clinically
meaningful change has occurred.
Interpretation of Serum Concentrations
Several factors can alter the relationship between AED serum concentration and the
patient’s response to the drug. Whenever a change in serum concentration is apparent,
pharmacokinetic factors (Table 60-4) should be considered (along with the patient’s
clinical status) before a decision is made to adjust the AED dosage. Laboratory
variability can cause minor fluctuations in reported AED serum concentrations.
Under the best conditions, reported values for serum concentrations may be within
plus or minus 10% of “true” values.
30 Therefore, the magnitude of any apparent
change must be considered. Published therapeutic ranges may have been determined
in small numbers of patients or may more accurately represent average serum
concentrations at usual doses. Inappropriate sample timing can result in inconsistent
and clinically meaningless changes in AED serum concentrations.
should be obtained in the morning, before any doses of the AED have been taken; this
practice provides reproducible, postabsorptive (i.e., “trough”) serum concentrations.
Interindividual variability in response to a given serum concentration of medication
is common. Excellent therapeutic response or even symptoms of intoxication may be
associated with AED serum concentrations that are classified as “subtherapeutic.”
Binding to serum proteins is significant for some AEDs (e.g., phenytoin, valproate,
tiagabine). Changes in protein binding can result from drug interaction, renal failure,
pregnancy, or changes in nutritional status. These changes can alter the usual
relationship between the measured total drug concentration (bound and unbound to
plasma proteins) and the unbound (pharmacologically active) drug concentration.
This change may not be apparent when only total serum concentrations are measured.
Determination of serum concentrations of free (i.e., unbound) AEDs is available from
many commercial laboratories; these determinations are expensive and results may
not be available for several days. If significant changes in protein binding are
suspected, measurement of free concentrations of AED may provide additional
information useful for adjustment of doses or interpretation of the patient’s
Monotherapy Versus Polytherapy
Decades ago, epilepsy was often treated initially with multiple AEDs (polytherapy).
A second, third, or even fourth drug was added when seizures were incompletely
controlled with a single AED. Evaluation of the effectiveness of polytherapy in
subsequent years has shown little advantage for most patients. Use of a single drug at
optimal tolerated serum concentrations produces excellent therapeutic results and
minimal side effects in most patients. Addition of a second AED significantly
improves seizure control in only 10% to 20% of patients.
elimination of existing polytherapy in patients with longstanding seizure disorders
often lessens or eliminates cognitive impairment and other side effects; seizure
Most experts advocate the use of a single AED (monotherapy) whenever possible.
Successful monotherapy may require higher-than-usual AED doses or serum
concentrations greater than the upper limit of the usual therapeutic range.
Addition of a second drug may be necessary in some patients; however, polytherapy
should be reserved for patients with multiple seizure types or for patients in whom
first-line AEDs have failed to control seizures when titrated to maximal tolerated
39 When a new AED is added to a patient’s regimen with the goal of
improving seizure control, the existing AED regimen should be scrutinized for
continued value. In some cases, a patient’s AED regimen can accumulate drugs that
may be unnecessary because they were started and never re-evaluated. Continued
vigilance and critical assessment of every drug in a patient’s regimen is important.
Use of polytherapy creates several disadvantages that must be weighed against
possible benefits. Seizure control may not significantly improve. Health care costs,
for medications and for increased laboratory monitoring, may increase significantly
with polytherapy. In addition, drug interactions among AEDs can complicate
assessment of the patient’s response and serum concentrations. Patient adherence
often is worsened when multiple medications are prescribed, and adverse effects
Although AED monotherapy is preferred whenever feasible, the recent
introduction of several new AEDs has increased the use of polytherapy.
limitations on the patient populations used for clinical trials of new drugs (i.e.,
patients with seizure disorders not completely controlled by previous medications),
most new AEDs are labeled only for use as add-on therapy. Although reports exist on
the efficacy of the new AEDs as monotherapy,
41–44 only felbamate, lacosamide,
lamotrigine, oxcarbazepine, and topiramate are US Food and Drug Administration
(FDA) approved for monotherapy. More AEDs will undoubtedly follow with
Duration of Therapy and Discontinuation of Antiepileptic Drugs
A diagnosis of epilepsy may not necessitate lifelong drug therapy. Several long-term
studies have shown that AED therapy may be successfully withdrawn from some
patients after a seizure-free period of 2 to 5 years.
10–12 Seizures recurred in only 12%
to 36% of patients who were followed for up to 23 years after AED withdrawal.
Therefore, many patients whose epilepsy is completely controlled with medication
can stop therapy after a seizure-free period of at least 2 years.
Pharmacokinetic Properties of Antiepileptic Drugs (AEDs)
Carbamazepine 90–100 Chronic: 5–25 2–4
Eslicarbazepine >90 Normal renal
Ethosuximide 90–100 Pediatric:
Lamotrigine 90–100 Monotherapy:
Levetiracetam 100 Normal renal
Phenobarbital 90–100 2–4 days 8–16
limits of most assay sensitivities.
Risk Factors Possibly Predicting Seizure Recurrence After Antiepileptic Drug
<2 years seizure-free before withdrawal
Onset of seizures after age 12
History of atypical febrile seizures
2–6 years before seizures controlled
Large number of seizures (>30) before control or total of >100 seizures
Partialseizures (simple or complex)
Abnormal EEG persisting throughout treatment
Slowing on EEG before medication withdrawal
Moderate to severe mental retardation
Discontinuation of medications is advantageous for economic, medical, and
psychosocial reasons. Costs associated with health care visits, serum concentration
determinations, and the medications themselves are eliminated or reduced. The risk
of adverse effects from long-term medication use is eliminated, and patients can
expect fewer lifestyle restrictions. Attempts to withdraw AED therapy are associated
with risks, however. Primary among them is the reappearance of seizure activity,
which can result in status epilepticus, loss of driving privileges, employment
difficulties, and/or physical injury.
Risk factors for seizure recurrence after discontinuation of AED have been
identified in observational studies; complete agreement, however, is not found among
studies regarding the nature and importance of specific risk factors. Opinions and
data also differ regarding the optimal duration of the seizure-free period before
discontinuation of AED is attempted. Nevertheless, at least some consensus has been
reached regarding certain factors that may predict a higher risk of seizure recurrence
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