Current Neuropharmacology, 2009, 7, 77-82
`
`77
`
`Antiepileptic Drug Monotherapy: The Initial Approach in Epilepsy
`Management
`
`Erik K. St. Louis1,*, William E. Rosenfeld2 and Thomas Bramley3
`
`1 Mayo Clinic, Rochester, Minnesota, USA; 2 St. Luke’s Hospital, St. Louis, Missouri, USA; 3 Xcenda, Salt Lake City,
`Utah, USA
`
`Abstract: Antiepileptic drug (AED) monotherapy is the preferred initial management approach in epilepsy care, since
`most patients may be successfully managed with the first or second monotherapy utilized. This article reviews the ration-
`ale and evidence supporting preferential use of monotherapy when possible and guidelines for initiating and successfully
`employing AED monotherapy. Suggested approaches to consider when patients fail monotherapy include substituting a
`new AED monotherapy, initiating chronic maintenance AED polytherapy, or pursuit of non-pharmacologic treatments
`such as epilepsy surgery or vagus nerve stimulation. Reducing AED polytherapy to monotherapy frequently reduces the
`burden of adverse effects and may also improve seizure control. AED monotherapy remains the optimal approach for
`managing most patients with epilepsy.
`
`Key Words: New onset epilepsy, antiepileptic drugs, monotherapy, titration.
`
`INTRODUCTION
`
` Epileptic seizures have been observed since antiquity
`[57]. Treatment preferences generally favored polytherapy
`prior to the evolution of modern antiepileptic drugs (AEDs).
`In the early 1900s, phenobarbital and the ketogenic diet were
`used to manage epilepsy. Throughout the earlier 20th century,
`the standard AEDs (phenytoin, phenobarbital, primidone,
`valproic acid, carbamazepine, and ethosuximide) were often
`combined in polytherapy use, due to the pervasive belief that
`polytherapy was more efficacious than monotherapy. How-
`ever, during the 1970s, several studies suggested that mono-
`therapy was equally efficacious, less toxic, and more toler-
`able than polytherapy [51,52]. Since then, most epilepsy
`experts have advocated monotherapy as the preferred ap-
`proach in epilepsy, although polytherapy is sometimes still
`necessary. This review examines the evidence favoring ini-
`tial monotherapy and suggests methods to maintain mono-
`therapy or reduce polytherapy to monotherapy when possi-
`ble.
`
`THE RATIONALE FAVORING MONOTHERAPY
`
`Since the early 1990s, the second-generation AEDs, fel-
`
`bamate, gabapentin, lamotrigine, topiramate, tiagabine, ox-
`carbazepine, levetiracetam, zonisamide, and pregabalin, have
`become available. Recently, the seemingly ever increasing
`armamentarium of AEDs has seen two additional newer
`(“third-generation”) AEDs released, lacosamide and rufina-
`mide. Advantages of most newer AEDs include a more de-
`sirable safety profile and fewer adverse effects and drug in-
`teractions than their predecessors. Recent pivotal clinical
`trials have provided evidence to support monotherapy use of
`second-generation AEDs [42]. Current treatment guidelines
`recommend monotherapy in most cases because data indicate
`
`
`*Address correspondence to this author at Department of Neurology, Mayo
`Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Tel: (507)
`538-1038; Fax: (507) 284-4074; E-mail: StLouis.Erik@mayo.edu
`
`similar efficacy and better patient tolerability compared to
`polytherapy [43-45,48,49,51,52]. Polytherapy may only
`minimally increase seizure control and can substantially in-
`crease AED toxicity, [9,20,43-45,48,49,51,52] drug interac-
`tions, [2,21,30,34,38,39,40,41] seizure aggravation [43,44],
`comorbid depression,[39] risk of sudden unexplained death
`in epilepsy patients (SUDEP), [28,36,37] noncompliance, [8]
`and cost [4]. Polytherapy and seizure burden were the two
`main causes of quality of life impairment in one recent sur-
`vey of epilepsy patients [58].
`
`WHO BENEFITS MOST FROM MONOTHERAPY?
`
` While monotherapy is preferable for most patients with
`epilepsy, monotherapy is particularly desirable for certain
`special patient populations, including women, elderly, and
`patients with co-morbid conditions (who are at increased risk
`for AED toxicity and drug interactions) [11,21,38]. Com-
`pared to polytherapy, monotherapy reduces the potential for
`adverse drug interactions. Hepatic and renal dysfunction
`significantly impacts the metabolism and elimination of
`many AEDs, which may reduce tolerability and safety of
`continued use. Pregnant women taking two or more AEDs
`are at substantially increased risk of fetal malformations (3%
`versus 15%) than mothers receiving monotherapy [11]. See
`Table 1 for a list of monotherapy recommendations.
`
`EVIDENCE SUPPORTING PREFERENTIAL MONO-
`THERAPY IN EPILEPSY
`
` The majority of patients with epilepsy respond to treat-
`ment with monotherapy; 47% of patients become seizure-
`free with the first AED tried, and another 13% achieve free-
`dom from seizures with the second monotherapy trial [24].
`
` While available evidence is central in determining
`whether an AED is effective for monotherapy usage, FDA
`approval and indication generally guide how an AED will be
`prescribed. First-generation AEDs were “grandfathered” by
`the FDA, receiving approval for monotherapy for a particular
`
`
`
`1570-159X/09 $55.00+.00
`
`©2009 Bentham Science Publishers Ltd.
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`78 Current Neuropharmacology, 2009, Vol. 7, No. 2
`
`Erik K. St. Louis
`
`Table 1. Monotherapy AED Options for Different Patient Populations: A Compilation of Practice Guidelines and Clinician
`Recommendations for the Treatment of Generalized Tonic-Clonic, Absence, Partial, and Myoclonic Seizures*‡†
`
`Patient Characteristic
`
`First Line
`
`Supporting Reference
`
`Elderly
`
`Lamotrigine or Levetiracetam
`
`Female of reproductive age
`
`Pregnant
`
`Liver failure
`
`Renal failure
`
`Depression
`
`Lamotrigine
`
`Lamotrigine
`
`Levetiracetam or Lamotrigine or Gabapentina
`
`Lamotrigine or Valproic acidb
`
`Lamotrigine or Valproic acidb or Oxcarbazepinec
`
`[26, 27]
`
`[25-27]
`
`[26, 27]
`
`[26, 27]
`
`[26, 27]
`
`[26, 27]
`
`aAbsence seizures only.
`bGeneralized tonic-clonic seizures only.
`cSimple partial and secondarily generalized tonic-clonic seizures only.
`
`*Pregabalin not available at time of these studies.
`‡Topiramate not recommended in any of these patient groups by Karceski and colleagues [23]; however, French et al. [17] recommends topiramate as monotherapy.
`†French et al. [17] evaluated second-generation AEDs only.
`
`seizure type without requirement to satisfy current rigorous
`approval requirements [42]. The majority of second-gene-
`ration AEDs are approved only as adjunctive therapies. Cur-
`rent FDA standards require superiority trial designs since
`placebo-controlled studies are considered unethical in epi-
`lepsy, and few such studies have been conducted given the
`practical difficulties and expense involved in such trials [42].
`United States practitioners are thus at the mercy of superior-
`ity trial design data produced by trials that are conducted for
`the purpose of gaining FDA approval, a somewhat artificial
`circumstance leaving practitioners in doubt as to how to util-
`ize the AED for monotherapy in clinical practice, unlike in
`Europe where approval standards permit the more practical
`standard of equivalence trial designs. As a result, many U.S.
`clinicians often continue to prescribe first-generation AEDs
`for new onset epilepsy because of experience and familiarity,
`limited comparative efficacy data with newer AEDs, and
`concern over the higher cost of newer drugs. To determine
`the best AED choices for monotherapy, further randomized,
`double-blind, long-term, comparative clinical trials with the
`newer AEDs are needed. Since few comparator studies are
`funded by industry, government agencies should become
`involved in conducting additional comparative clinical trial
`studies, and independent groups (ie, International League
`Against Epilepsy) should be persuaded to collect data from
`historically treated and control patients.
`
` Currently, four second-generation AEDs are FDA ap-
`proved for use as monotherapy, with some limitations; these
`are oxcarbazepine, lamotrigine, topiramate, and felbamate
`[17]. In four randomized, controlled, blinded trials, oxcar-
`bazepine demonstrated efficacy as monotherapy in patients
`with partial seizures [36,60]. Lamotrigine is currently ap-
`proved as monotherapy when converting from an enzyme-
`inducing AED or valproate but not for de novo or initial
`monotherapy [17]. However, lamotrigine should be used
`with caution in persons under the age of 16 due to a higher
`incidence of a potentially life-threatening rash in pediatric
`patients, [27] and patients receiving concurrent valproic acid
`or who receive inappropriately fast initial titration of lamo-
`
`trigine are also at heightened risk of serious rash [34]. Topi-
`ramate is indicated as initial monotherapy in adults and chil-
`dren aged 10 years and older with partial onset or primary
`generalized seizures; efficacy was established in both a large,
`double-blind, dose-controlled study and a second large trial
`comparing two doses of topiramate with standard compara-
`tors carbamazepine and valproate [3,17,59]. Felbamate also
`has evidence for monotherapy use in partial-onset seizures;
`however, severe idiosyncratic toxicities limit its use [15,16].
`Additionally, gabapentin possesses adequate evidence for
`confident use as monotherapy in treatment of partial-onset
`seizures, although it lacks formal FDA approval for this in-
`dication [10,17].
`
` Among the second-generation AEDs approved for mono-
`therapy use, few comparator trials have been conducted.
`Gabapentin and lamotrigine have been shown to be compa-
`rably effective and tolerable in two large prospective trials,
`and were more tolerable than carbamazepine in elderly with
`newly diagnosed epilepsy [6]. A large, naturalistic, un-
`blinded controlled trial recently demonstrated superior effi-
`cacy (for time to treatment failure) of lamotrigine as com-
`pared to carbamazepine, oxcarbazepine, and topiramate [31].
`
` The other second-generation and third-generation AEDs
`have not been FDA approved for monotherapy use since
`most lack an adequate level of evidence for this indication.
`However, the efficacy and tolerability of levetiracetam
`monotherapy for treatment of partial-onset seizures has been
`confirmed in a recent large, prospective, comparator trial
`against carbamazepine [7]. Small controlled clinical trials are
`also available to support tiagabine monotherapy use [47].
`
`GUIDELINES FOR AED MONOTHERAPY
`
` Given the complexity and expansive body of evidence
`concerning AED therapy in the medical literature and limita-
`tions in practical application of this literature to actual pa-
`tients, practice guidelines and expert surveys are valuable
`tools to assist clinicians in applying evidence based practice
`for patients with epilepsy. Practice guidelines are available to
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`Antiepileptic Drug Monotherapy
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`Current Neuropharmacology, 2009, Vol. 7, No. 2 79
`
`assist practitioners in the management of new-onset and re-
`fractory epilepsy and epilepsy in women. The American
`Academy of Neurology/American Epilepsy Society (AAN/
`AES) Practice Guidelines for the treatment of new-onset
`epilepsy identified gabapentin, lamotrigine, oxcarbazepine,
`and topiramate as possessing Class I evidence (prospective
`study, blinding, statistical population-based sample, and pa-
`tients studied concurrently and early in the course of therapy)
`for use as monotherapy in the treatment of new-onset partial
`or mixed seizures [18]. The recently updated guidelines for
`the treatment of epilepsy in women state that in women with
`epilepsy (WWE), monotherapy is recommended during the
`reproductive years to reduce the risk of teratogenicity seen
`with polytherapy [1].
`
` A recent survey of epilepsy experts found that lamo-
`trigine, levetiracetam, and valproic acid are preferred AED
`choices for monotherapy in the treatment of generalized
`tonic-clonic, absence, and myoclonic seizures [23]. Previous
`survey results were compared to the current survey, and,
`overall, valproic acid is still the drug of choice for each of
`these seizure types, except for absence seizures, where etho-
`suximide remains the preferred AED. Many practitioners
`chose lamotrigine and topiramate as first-line treatment for
`generalized tonic-clonic seizures.
`
`HOW TO INITIATE MONOTHERAPY
`
`Practical tenets for achieving successful monotherapy in
`
`new-onset epilepsy management include the following: 1)
`select an efficacious AED for the specific seizure type; 2)
`choose an AED with a tolerable adverse effect and toxicity
`profile; and 3) titrate the AED slowly to the desired dose,
`taking into account the patient’s response to treatment. If the
`first AED monotherapy is ineffective, adding a second AED,
`then tapering and discontinuing the ineffective AED, is the
`preferred approach [56]. When switching AEDs, selecting an
`agent with a different MOA may increase the likelihood of a
`successful treatment response. If the second sequential AED
`monotherapy is ineffective, an adjunctive AED with a differ-
`ent and potentially complementary MOA should be consid-
`ered for use in adjunctive polytherapy. Since approximately
`35% of patients with epilepsy will not respond to monother-
`apy, most refractory patients become candidates for poly-
`therapy [24,26]. Polytherapy with lower or moderate dosages
`of two AEDs may also sometimes be preferred for manage-
`ment of refractory patients who have dose-limiting neuro-
`toxic adverse effects with high-dose monotherapy [24].
`
` Before initiating treatment, patients with epilepsy should
`undergo a thorough medical evaluation to determine seizure
`type and consider baseline patient characteristics that may
`influence the decision of whether treatment is necessary and,
`if so, which AED may be the most logical choice. Evaluation
`to determine the patient’s epilepsy syndrome begins with a
`thorough clinical history, including a detailed description of
`the seizure semiology, an awake and asleep electroencepha-
`logram (EEG), and a brain magnetic resonance image (MRI).
`A standard brain MRI is adequate in newly diagnosed epi-
`lepsy where the priority is to exclude underlying serious
`symptomatic pathologies, such as arteriovenous malforma-
`tions or neoplasms. However, when feasible, available, and
`of reasonable cost, it is advantageous to consider obtaining
`
`brain MRI with a volumetric seizure-protocol study in pa-
`tients with suspected partial-onset seizures, given better
`identification of subtle mesial temporal lobe pathologies
`such as hippocampal sclerosis or malformations of cortical
`development that may impact on prognosis for drug respon-
`siveness, as well as future decisions regarding surgical triage
`if the patient becomes refractory to AEDs.
`
` Educating the patient about epilepsy, AED compliance,
`and seizure first-aid is important for ensuring successful
`therapy. AED selection is determined by seizure type, patient
`medical history, and concurrent medications. For partial epi-
`lepsy, any approved AED could be considered for use (ex-
`cept ethosuximide, which is ineffective for partial-onset sei-
`zure treatment). In idiopathic or symptomatic generalized
`epilepsies, as well as for ambiguous or unknown epilepsy
`syndromes, a broad-spectrum AED should be preferentially
`utilized given the potential to treat (or avoid aggravation of)
`other potentially associated generalized seizure-types in gen-
`eralized epilepsies (i.e., absence and myoclonic seizures in
`idiopathic generalized epilepsies, or tonic seizures in symp-
`tomatic generalized epilepsy).
`
` Once an AED has been selected, starting with a low dose
`and gradually titrating to a moderate and presumably effec-
`tive dose is a reasonable strategy, since titration to doses
`higher than a mean effective dosage are often poorly toler-
`ated and only provide additional efficacy in perhaps 10% to
`15% of patients [24]. A more rapid titration may be neces-
`sary in selected patients who have had multiple recent sei-
`zures. Maximizing the dose is only recommended in patients
`who do not respond to moderate doses. At each patient visit,
`it is necessary to conduct a detailed assessment of AED ther-
`apy, including adverse effects and compliance. Utilizing a
`quantitative survey of patient’s perceived adverse effects
`such as the adverse events profile (AEP) has been shown to
`improve physicians’ ability to detect adverse effects of
`treatment and appropriately alter antiepileptic drug therapies
`to improve quality of life [19]. The impact of adverse effects
`on daily living should be discussed, and any barriers to com-
`pliance should be addressed.
`
`WHY ARE SOME PATIENTS REFRACTORY TO
`MONOTHERAPY?
`
` The efficacy of currently available AEDs is limited to
`reduction of seizure frequency, and no AED has yet been
`proven to impact the pathophysiology of epilepsy itself [55].
`Currently, there is no convincing evidence that any of the
`available AEDs are anti-epileptogenic, nor has any AED
`been shown to favorably impact the long-term outcome of
`epilepsy [24]. Yet, prescribing an AED after a second or
`third seizure event is the accepted practice standard, based
`on logic derived in part from epidemiologic studies of the
`natural history of new onset unprovoked seizures that con-
`firm a greatly increased risk for further seizure recurrence
`following the occurrence of a second unprovoked seizure
`[22]. The desired short-term outcomes of epilepsy manage-
`ment are seizure freedom, seizure control when complete
`seizure freedom is not possible, and maximizing patient
`quality of life, given that the complications of untreated sei-
`zure activity are increased risk of injury and mortality, cog-
`nitive and behavioral abnormalities, and social disadvantage.
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`Erik K. St. Louis
`
`Currently, there is no AED for the treatment of epilepsy that
`is completely effective, without adverse effects, and effica-
`cious for all patients. Of the older AEDs, carbamazepine was
`shown to be the most effective and tolerable AED in two
`pivotal clinical trials; thus, it became the standard to which
`developing AEDs have been compared, [7,31-33] although
`carbamazepine itself has never been compared to placebo or
`demonstrated efficacy in an active control-designed study.
`Most studies have shown that newer AEDs have equivalent
`efficacy to that of carbamazepine, but several newer AEDs
`have superior tolerability including lamotrigine and gabapen-
`tin [6,46]. However, recently published comparator trials of
`newer AEDs against a sustained release form of carba-
`mazepine have shown relatively equivalent tolerability, sug-
`gesting that immediate release forms of carbamazepine may
`be less tolerable and sustained release forms of carba-
`mazepine are equally tolerable to newer AEDs [7,31].
`
`WHY DOES MONOTHERAPY FAIL?
`
` AED monotherapy may fail for a variety of reasons, in-
`cluding errant diagnosis (eg, mistaking syncopal spells as
`seizures), inaccurate diagnosis of seizure type leading to
`ineffective AED choice (eg, mistaking partial complex sei-
`zures for absence with prescription of carbamazepine rather
`than ethosuximide or valproate), intolerable adverse effects
`(eg, depression, sedation, cognition problems), idiosyncratic
`reactions (eg, rash, aplastic anemia, hepatoxicity), noncom-
`pliance, over treatment, [50] and pharmacogenetic factors
`[53]. Monotherapy is most likely to be effective if the clini-
`cian develops a personalized treatment plan that is appropri-
`ately customized for the individual patient, provides the pa-
`tient with suitable education concerning the drug chosen, and
`offers the opportunity for close telephone follow-up and sur-
`veillance with evolution of any adverse effects to enable
`prompt feedback and modification of the titration scheme or
`target dose.
`
` Monotherapy may be ineffective when the AED choice is
`suboptimal for a particular patient type. Certain AEDs are
`arguably best avoided in certain patient types, such as pheny-
`toin or carbamazepine in the elderly [21,29] (given their vul-
`nerability for adverse effects, osteoporosis, and drug interac-
`tions) or valproate in women of child-bearing potential
`(given its heightened teratogenic risk) [11]. AEDs that re-
`quire substantial hepatic metabolism are best avoided in pa-
`tients with liver disease. Carbamazepine, phenytoin, pheno-
`barbital, primidone, oxcarbazepine, and high-dose topiramate
`are enzyme inducers; these agents increase the hepatic me-
`tabolism of concurrently administered drugs, endogenous
`and exogenous sex hormones, and vitamin D. Enzyme-
`inducing AEDs can lead to: therapeutic failure of other in-
`ducible AEDs and other drugs such as anticoagulants, hor-
`monal contraceptives, lipid-lowering agents, and antihyper-
`tensives; reproductive dysfunction; and osteopenia or frank
`osteoporosis [21,40,41]. Primidone and phenobarbital are not
`commonly recommended as first-line therapies due to poor
`tolerability and efficacy as well as abuse potential. Felba-
`mate is associated with rare but potentially fatal idiosyncratic
`hematologic and hepatic toxicities, limiting its use solely to
`brittlely refractory patients [16].
`
` Overtreatment may be another cause of failure [14]. Ap-
`proximately 50% of patients with new onset epilepsy achieve
`remission with moderate doses of the first AED prescribed
`[26]. When a moderate dose fails, maximizing the dose re-
`sults in up to 10-25% of patients obtaining seizure control,
`[25] but at the risk of adverse events. Rarely, some epilepsy
`patients may experience a paradoxical increase in seizure
`frequency or severity at higher AED doses [54]. If no im-
`provement or a worsening in seizure activity is seen, the
`AED dose should be reduced or the drug discontinued.
`
`WHAT TO DO WHEN MONOTHERAPY FAILS
`
`Patients who do not achieve seizure freedom on an ap-
`
`propriately selected and optimally administered initial AED
`monotherapy are unlikely to become seizure free on future
`AED trials [25]. If the patient is experiencing breakthrough
`seizures while receiving moderate doses of an AED, increas-
`ing the dosage of that AED until the patient has either be-
`come clinically toxic or has shown a clear plateau in re-
`sponse to the medication is reasonable. If the patient has
`continued breakthrough seizures at this point, transition to a
`second monotherapy is indicated. Approximately two-thirds
`of epilepsy patients will have adequate seizure control with
`either the first or second trial of AED monotherapy [25]. The
`remaining third are considered to have refractory epilepsy. If
`a second monotherapy also fails, consideration of initiating
`AED polytherapy by adding a drug with a different and
`complementary principle mechanism of action should be
`considered. While monotherapy is preferable to polytherapy,
`some patients will require more than one AED to attain suc-
`cessful seizure control [12,13]. In refractory patients receiv-
`ing polytherapy, the treatment goal necessarily shifts some-
`what from the goal of producing seizure freedom, which is
`increasingly improbable, to effecting palliation and control
`of seizures while minimizing adverse effects. Since refrac-
`tory patients rarely attain seizure-freedom with polytherapy,
`many require evaluation for alternative non-pharmacologic
`treatments such as resection surgery or vagus nerve stimula-
`tion (VNS).
`
`Patients who subsequently become refractory to the first
`
`or second empiric AED monotherapy should be strongly
`considered for ictal seizure recording with video-EEG moni-
`toring to ensure that the epilepsy diagnosis is accurate, and if
`so, to establish the correct epilepsy syndrome diagnosis.
`Video-EEG monitoring allows an accurate diagnosis of the
`seizure-type, which may enable the clinician to appropriately
`tailor AED therapy and explore the patient’s potential candi-
`dacy for resection surgery or VNS therapy. Video-EEG
`monitoring also ensures exclusion of diagnoses that mimic
`epilepsy, such as psychogenic non-epileptic spells (ie, pseu-
`doseizures), a particularly common finding representing be-
`tween 30-50% of admissions to most epilepsy monitoring
`units. In such cases, AEDs may in most cases be tapered and
`discontinued, with referral to appropriate psychological
`counseling resources, and when necessary, psychiatric care.
`More rarely, physiologic non-epileptic spells such as syn-
`cope or sleep disorders are instead identified in some patients
`with suspected epilepsy, and appropriate referral to other
`specialists can be offered.
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`Current Neuropharmacology, 2009, Vol. 7, No. 2 81
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`CONVERTING FROM POLYTHERAPY TO MONO-
`THERAPY
`
`Patients may begin receiving polytherapy while transi-
`
`tioning from one trial of monotherapy to another (transitional
`monotherapy), or because of two failed attempts with mono-
`therapy (chronic polytherapy). In the first situation, eventual
`monotherapy is likely to result once the original AED is ta-
`pered off. However, in the latter case, patients may continue
`on multiple AEDs indefinitely. While receiving multiple
`AEDs, some patients may go into seizure remission, while
`other patients will continue to require sequential trials of
`additional AEDs (AED sequencing). Patients who are appro-
`priate candidates for tapering one or more AEDs are those
`who have been seizure free for 2 years or longer. For these
`patients, a slow taper is recommended, with dose reductions
`occurring weekly or every other week. Additionally, patients
`receiving unsuccessful polytherapy (ie, polytherapy that has
`failed to produce seizure freedom or that is resulting in intol-
`erable adverse effects) should be considered for a further
`trial of monotherapy or additional AED sequencing.
`
`CONCLUSIONS
`
` Epilepsy treatment often requires lifelong medication
`management. Monotherapy is preferred when managing pa-
`tients with epilepsy, given similar efficacy and superior tol-
`erability compared to polytherapy for most patients, espe-
`cially those with newly diagnosed epilepsy who are not re-
`fractory to other treatments. While preferred for initial use in
`epilepsy treatment, monotherapy may also fail for a variety
`of reasons. Monotherapy may fail in patients who do not
`receive thorough evaluation and counseling by their physi-
`cian. Patients need to have a clear understanding of treatment
`expectations candidates for tapering of one or more AEDs.
`Adverse effects, noncompliance, and evolving refractory
`epilepsy are the principle reasons for treatment failure. To
`increase the likelihood of successful monotherapy, clinicians
`should consider individual patient characteristics, including
`seizure type, potential drug interactions, likelihood of com-
`pliance, and cost, while realizing that therapy may require
`modification. Vigilance for need of further medication titra-
`tion or tapering, the patient’s current seizure frequency and
`severity, and occurrence of adverse effects is necessary for
`successful monotherapy in epilepsy care.
`
`ACKNOWLEDGEMENT
`
` The authors are grateful for secretarial assistance with
`manuscript formatting by Ms. Laura Disbrow, Mayo Clinic
`Department of Neurology.
`
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