Indian Journal of Pediatrics (October 2021) 88(10):993–999

https://doi.org/10.1007/s12098-021-03857-8

REVIEW ARTICLE

A Review of the Selected and Newer Antiseizure Medications Used

in Childhood Epilepsies
Samata Singhi1 · Ajay Gupta2

Received: 7 January 2021 / Accepted: 11 June 2021 / Published online: 10 August 2021
© Dr. K C Chaudhuri Foundation 2021

Abstract
There have been additions of newer antiseizure medications in the armamentarium of clinicians for the management of
epilepsy. The newer antiseizure medications have advantages of better tolerability, lesser adverse effects, and minimal drug
interactions in comparison with conventional antiseizure medications. However, high cost and availability are concerns.
There are also peculiar pharmacokinetic and pharmacodynamic considerations for the pediatric age, particularly in the context
of age-dependent electroclinical syndromes and precision-based medicine. This review attempts to provide a com-
prehensive and pragmatic update on newer antiseizure medications.

Keywords  Antiseizure medications · Childhood epilepsy

Introduction [1–3]. They do not have as significant hepatic induction or

About 70% of epilepsy patients will achieve seizure free-
dom with antiseizure medications (ASMs). The choice of
ASMs usually depends on seizure classification, epilepsy
syndrome, safety of ASM, side-effect profile, and patient
comorbidities. Sometimes, additional factors, such as avail-
able formulations for ease of administration, need for rapid
vs. slow titration, intravenous vs. oral administration in
newly diagnosed hospitalized patients, synergistic polyther-
apy, and mechanism and duration of action of ASMs also
influence the selection. Combination of ASMs with similar
mechanism of action should be avoided since side effects
are typically increased with such regimen. ASMs developed
after 1993 are considered to be the newer ASMs. While effi-
cacy of the newer ASMs is comparable to the older ones,
advantages include minimal drug-drug interactions, better
pharmacokinetic profiles, and minimal long-term side effects
* Samata Singhi
samata.singhi@gmail.com
1
Department of Neurology, Kennedy Krieger Institute
and Johns Hopkins School of Medicine, Baltimore,
MD 21205, USA
2
Pediatric Epilepsy, Epilepsy Center, Department
of Neurology/Neurological Institute, Cleveland Clinic Lerner
College of Medicine, Cleveland Clinic, 9500 Euclid Avenue,
Cleveland, OH 44195, USA
inhibition as previous ASMs.
The purpose of this article is to succinctly discuss key
points of selected newer ASMs to facilitate their informed
use in clinical practice. Common dosing parameters are out-
lined in Table 1.
Cannabidiol
Cannabidiol is indicated for the treatment of seizures asso-
ciated with Lennox–Gastaut syndrome (LGS) or Dravet
syndrome in patients 2 y of age and older. The US Federal
Drug Administration (FDA) in July 2020 approved the use
of cannabidiol for the treatment of seizures associated with
tuberous sclerosis complex (TSC) in patients 1 y of age and
older. The mechanism of antiseizure action of cannabidiol is
claimed to be unique involving cannabidiol receptor modu-
lation, but is not well understood. Common adverse effects
include somnolence, decreased appetite, diarrhea, fatigue,
malaise, asthenia, rash; insomnia, sleep disorder and poor-
quality sleep. Hypersensitivity reactions may occur. Canna-
bidiol can cause dose-related transaminase elevations, and
the risk is increased with concomitant use of valproate and,
to a lesser extent with clobazam [4]. Serum transaminase
and total bilirubin levels should be obtained at baseline and
then at 1, 3, and 6 mo after starting treatment, and periodi-
cally thereafter as clinically indicated.

Vol.:(0123456789)

994 Indian Journal of Pediatrics (October 2021) 88(10):993–999

Table 1  Summary of dosing for newer antiseizure medications

Drug name Starting dose Maintenance dose Tests/Considerations

Clobazam Under 12 y: 0.1 mg/kg/d
Over 12 y: 5–10 mg/d
Cenobamate Adults: 12.5 mg daily
Cannabidiol 5 mg/kg/d
Eslicarbazepine 400 mg daily
Fenfluramine 0.1 mg/kg twice daily
Felbamate Under 12: 15 mg/kg/d
Over 12 y: 1200 mg/d
Lacosamide 100 mg daily div BID (adults) 200–400 mg/d div BID
Lamotrigine 2–12 y:
With VPA: 0.15 mg/kg/d
With enzyme-inducer:
0.6 mg/kg/d
Over 12 y:
Monotherapy: 25 mg daily
With VPA: 25 mg every other 200–400 mg/d div BID
day
With enzyme-inducer: 50
mg/day
Levetiracetam Under 12 y: 20–30 mg/kg/d
Over 12 y: 250–500 mg/d
Oxcarbazepine 2–16 y: 5–10 mg/kg/d
Adults: 300 mg/d
Perampanel 2 mg once daily at bedtime
Rufinamide Over 4 y and under 30 kg:
Without VPA: 10 mg/kg/d
With VPA: 5 mg/kg/d
Over 4 y and over 30 kg
Without VPA: 200 mg
With VPA: 5 mg/kg/d
Stiripentol 25–50 mg/kg/d
Topiramate Under 12 y: 0.5–1 mg/kg/d
Over 12 y: 25–50 mg/d
Vigabatrin Children: 20–40 mg/kg/d
IS: 50 mg/kg/d
Adults: 500 mg/d
Zonisamide 2–4 mg/kg/d
0.4–0.8 mg/kg/d CBC, LFT; Use with caution in OSA and pulmonary
20–40 mg/d disease
150–200 mg daily, max 400 mg Slow titration to reduce risk of DRESS; Do not use
in short QT syndrome
10 mg/kg/d div BID, max 20 mg/kg/d LFT
800–1200 mg daily BMP, LFT
Without stiripentol: 0.35 mg/kg twice EKG at baseline, then every 6 mo
daily (max 26 mg daily)
With CLB and stiripentol: 0.2 mg/kg
twice daily (max 17 mg daily)
30–60 mg/kg/d div BID CBC, LFT at baseline, 1 mo, and then at least
2400–5000 mg/d div BID every 3 mo
CBC, LFT; EKG at baseline
BMP, LFT; Very slow titration to decrease risk of SJS
1–5 mg/kg/d div BID
5–15 mg/kg/d div BID
100–200 mg/d div BID
100–200 mg/d div BID
20–60 mg/kg/d, up to 100 mg/kg/d div BID
2000–3000 mg/d div BID
30–45 mg/kg/d div BID BMP, LFT; Use cautiously in those with hypersen-
600–2400 mg/d div BID sitivity to carbamazepine
8–12 mg once daily at bedtime Monitor for suicidal thoughts or
behavior
1000 mg/d div BID 400–600 mg/d div BMP, LFT; EKG at baseline;
BID Do not use in short QT syndrome
1800 mg (30–50 kg), 2400 mg (50–
70 kg), 3200 mg (> 70 kg)
50–100 mg/kg/d div BID or TID, max 4 g BMP, CBC, LFT
3–9 mg/kg/d div BID BMP, CBC, LFT
100–600 mg/d div BID
40–60 mg/kg/d BMP, CBC, LFT; Visual field examination at baseline
150–200 mg/kg/d div BID and then every 6 mo
1000–3000 mg/d div BID
4–8 mg/kg/d (daily or div BID), max
12 mg/kg/d

BID bis in die (twice daily); BMP Basic metabolic panel; CBC Complete blood count; DRESS Drug reaction with eosinophilia and systemic
symptoms; EKG Echocardiogram; IS Infantile spasms, Kg Kilograms, LFT Liver function tests; Mg Milligrams; SJS Stevens Johnson syndrome;
OSA Obstructive sleep apnea; VPA Valproate
For precise dosing information, please refer to the following original sources:
Patsalos P.N. and E.K. St Louis, The Epilepsy Prescriber’s Guide to Antiepileptic Drugs. 3 ed. 2018, Cambridge: Cambridge University Press
Epidiolex prescribing information. Available from: Epidiolex prescribing information. https://​www.​acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​
2018/​21036​5lbl.​pdf
Cenobamate prescribing information. Available from: https://​www.​acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​2019/​21283​9s000​lbl.​pdf
Highlights of Fenfluramine prescribing information. Available from: https://​www.​acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​2011/​20208​8s001​
lbl.​pdf
Indian Journal of Pediatrics (October 2021) 88(10):993–999
Cenobamate
In the United States, cenobamate is FDA approved for treat-
ment of focal seizures in adults. Cenobamate is thought to
decrease neuronal excitability by enhancing the fast and slow
inactivation of sodium channels and by inhibiting the persis-
tent component of the sodium channel current. The most com-
mon adverse effects include somnolence, fatigue, dizziness,
gait disturbance, diplopia, headache and cognitive dysfunction
including memory impairment, disturbance inattention, amne-
sia, confusional state, aphasia, speech disorder, and psychomo-
tor retardation [5]. Serious reactions include drug reaction with
eosinophilia and systemic symptoms (DRESS), QT shorten-
ing, suicidal behavior and ideation [6]. It is contraindicated in
patients with familial short QT syndrome [7]. Slow titration is
recommended to reduce risk of DRESS.
Clobazam
In the United States, clobazam is FDA approved as adjunc-
tive therapy for treatment of seizures associated with LGS
in patients aged 2 y or older. However, in other countries it
is approved for treatment of focal or generalized seizures,
nonconvulsive status epilepticus as well as monotherapy for
catamenial seizures. Clobazam works by binding to the ben-
zodiazepine receptor at the G ­ ABAA ligand-gated chloride
channel complex and thereby enhancing the inhibitory effects
of γ-aminobutyric acid (GABA). Clobazam can potentiate
the effects of central nervous system (CNS) depressants such
as alcohol, benzodiazepines, and barbiturates [8]. Clobazam
can increase plasma levels of phenytoin, carbamazepine, val-
proic acid, and stiripentol. Effectiveness of some hormonal
contraceptives may be diminished with coadministration of
clobazam [8]. Common side effects include sedation [9],
drowsiness, fatigue, hyposalivation, loss of appetite, consti-
pation, behavioral and cognitive side effects, and restlessness
[10]. Severe aggressive outbursts, hyperactivity, insomnia, and
depression with suicidal ideation may occur, particularly in
children. Physical dependence may be seen with long duration
treatment with large doses. Serious or life-threatening but rare
adverse effects include Stevens–Johnson syndrome (SJS) or
toxic epidermal necrolysis (TEN) [8]. Respiratory depression
may be seen with high doses. Rarely, amnesia and nystagmus
may be seen [10]. It may be less effective than clonazepam in
myoclonic jerks and absences.
Eslicarbazepine
Eslicarbazepine is FDA indicated as monotherapy and for
adjunctive treatment of focal seizures in patients aged 4 y or
older. Eslicarbazepine acts by blocking sodium channels and
stabilizing their inactive state [11]. Common adverse effects
995
include dizziness, headache, diplopia, somnolence, vertigo,
nausea, vomiting, fatigue, tremor, and ataxia [12]. It has also
been associated with hyponatermia [13]. Rare but serious
adverse reactions may include SJS, TEN, anaphylactic reaction
and angioedema, DRESS, bone marrow depression, and serious
cardiac arrhythmias [13]. Eslicarbazepine should not be used in
patients with a history of hypersensitivity due to oxcarbazepine
or carbamazepine. Eslicarbazapine increases the PR interval;
therefore, patients with AV block may be at risk of myocardial
infarction [10]. Eslicarbazepine could be considered a first-line
monotherapy for focal seizures, with tolerability advantages
over immediate-release oxcarbazepine [14].
Felbamate
Felbamate is FDA approved as monotherapy or adjunctive
therapy in the treatment of focal seizures in adults with epi-
lepsy and adjunctive therapy in treatment of focal and gener-
alized seizures associated with LGS in children. It is recom-
mended only in patients whose epilepsy is so severe that the
risk of aplastic anemia and/or liver failure is deemed accept-
able.Felbamate has several mechanisms of action includ-
ing inhibition of N-methyl-D-aspartate (NMDA)-induced
intracellular calcium currents, potentiation of GABA, block-
ing sodium channels, and inhibition of excitatory NMDA
responses at high concentrations [15]. Felbamate may
increase serum concentrations of phenobarbital, phenytoin,
valproate [16–18], clobazam, and lamotrigine [10]. Common
adverse effects include anorexia, nausea, vomiting, dyspep-
sia, insomnia, irritability, dizziness, somnolence, diplopia,
headache, weight loss, and tremor [19]. Gastric symptoms
may be alleviated by concurrent administration with food.
Serious and life-threatening adverse effects include aplastic
anemia in about 1 in 5000 [10]. Aplastic anemia has not
been reported in children under 13 [20]. Hepatic failure is
seen in about 1 in 26,000 patients [10, 20]. Rarely, choreo-
athetosis or dystonia may be seen. Because of its potentially
serious adverse effects, felbamate is not indicated as first-
line therapy for any type of seizure [14].
Fenfluramine
Fenfluramine is approved for the treatment of seizures asso-
ciated with Dravet syndrome in patients 2 y of age and older.
Fenfluramine can cause decreased appetite, somnolence,
sedation, lethargy [21, 22], fatigue, malaise, ataxia, increased
blood pressure, and drooling [23]. It is associated with car-
diac valvulopathy or pulmonary hypertension. Mydriasis
and precipitation of angle-closure glaucoma have been
reported. Serotonin syndrome may occur, particularly with
concurrent use of other serotonergic drugs. Concomitant

996
use of fenfluramine with MAOIs is contraindicated [23]. It
is recommended to obtain an echocardiogram before treat-
ment with fenfluramine, then every 6 mo during treatment,
and 3 to 6 mo post-treatment to evaluate for valvular heart
disease and pulmonary hypertension. Because of the risks of
valvular heart disease and pulmonary arterial hypertension,
fenfluramine is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS)
in the United States.
Gabapentin (Neurontin)
Gabapentin (Neurontin) is a narrow spectrum drugwith rela-
tively weak efficacy compared to other ASMs. It is indicated
as adjunctive therapy for focal seizures in patients aged 3 y
or older. It may cause exacerbation of myoclonus and other
generalized seizures [24]. Gabapentin is not frequently used
in children for management of seizures.
Lacosamide
Lacosamide is an effective option of treatment of focal and
generalized seizures with good efficacy in children as well. It
is FDA indicated for monotherapy or adjunctive treatment of
focal seizures in patients aged 4 y or older. It has also been used in
status epilepticus.Lacosamide enhances slow inactivation of
sodium channels resulting in stabilization of hyperexcitable
neuronal membranes [10, 25]. Dose related adverse effects
include dizziness, headache, nausea, diplopia, memory
impairment, tremor, nystagmus and sedation. These may be
exacerbated when lacosamide is used in combination with
another sodium channel blocking drug [26]. It may also
increase the PR interval therefore patients with second or
third degree atrioventricular block may be at risk of severe
bradycardia or syncope [10]. Hyperammonemic encepha-
lopathy may occur in combination with valproic acid.
Lamotrigine
Lamotrigine is a broad spectrum antiseizure drug and is
FDA approved as adjunctive therapy for focal seizures,
generalized tonic–clonic seizures and generalized seizures
of LGSin patients aged 2 y or older. In the UK it is also indicated
for monotherapy oftypical absence seizures. Lamotrigine
blocks sodium channels [14] and inhibits glutamate release.
It also inhibits high voltage calcium channels [20]. Adverse
effects include dizziness, ataxia, blurred vision, diplopia,
nausea, vomiting, headache, insomnia and tremor and are
dose related. Rash is seen in about 3%–10% of cases [14].
The risk of serious rash, including SJS and TEN is 1 in 1000
Indian Journal of Pediatrics (October 2021) 88(10):993–999
in patients over 12 y old but 1 in 100 in children under 12
y of age, and the risk increases with coadministration with
valproate, faster titration, and higher doses [14]. Typically
the rash may occur within 8 wk of lamotrigine initiation or
if the medication is stopped and resumed at normal dose
[10]. Consequently, lamotrigine is titrated very slowly, and
even slower in the presence of valproate. Rare hematological
abnormalities my also occur including neutropenia, leuko-
penia, thrombocytopenia, pancytopenia, and rarely, aplastic
anemia and agranulocytosis. Lamotrigine may also increase
the risk of cardiac arrhythmia. Rare adverse effects include
tics and chorea, aseptic meningitis, and photosensitivity
[10]. Lamotrigine may exacerbate myoclonic seizures in
some patients such as juvenile myoclonic epilepsy (JME)
or juvenile absence epilepsy. It is favored in women of child-
bearing age given its low rates of teratogenicity.
Levetiracetam
Levetiracetam is a broad spectrum antiseizure drug and
represents first line or second line therapy in generalized
epilepsies as well as focal seizures. FDA indications for use
of levetiracetam include focal seizures in adults and children 
aged 1 mo or older, adjunctive therapy for myoclonic seizures in
adults and adolescents aged 12 y or older with JME and adjunc-
tive therapy for primary generalized tonic clonic seizures in
adults and children aged 6 y or older with idiopathic generalized
epilepsy. Levetiracetam binds to the synaptic vesicle protein
2A and can partially inhibit N-type calcium currents [10].
Levetiracetam does not have any major interactions with
other antiseizure medications and does not enhance metab-
olism of oral contraceptives. Topiramate related adverse
effects may be exacerbated in children coadministered with
levetiracetam. Adverse effects include somnolence, dizziness
and asthenia. Behavioral symptoms including agitation, hos-
tility, oppositional behavior, anxiety, aggression, depression,
and emotional lability may be seen in children [10]. Rare
activation of suicidal ideation may be seen. Levetiracetam
has an excellent safety profile, does not cause significant
idiosyncratic reactions, does not have any major medical
interactions and is usually one of the first ASM that is pre-
scribed in real world practice in most new onset epilepsies
in children and adults.
Brivaracetam
Brivaracetam is an FDA-approved as monotherapy or
adjunctive therapy for focal-onset seizures in patients 4
y of age and older. It may cause dose-dependent somno-
lence, fatigue, malaise, sedation, and lethargy. In addition,
treatment with brivaracetam is associated with dizziness,
Indian Journal of Pediatrics (October 2021) 88(10):993–999
vertigo, ataxia, and nystagmus [27]. Irritability, anxiety,
aggression, anger, agitation, and depression, and psychotic
symptoms, such as paranoia and acute psychosis may also
occur [28].
Oxcarbazepine
Oxcarbazepine is indicated as monotherapy or adjunctive
therapy for focal seizures in patients aged 4 y or older. Oxcar-
bazepine blocks voltage gated sodium channels resulting in
stabilization of hyperexcited neural membranes, inhibition
of repetitive neuronal firing and decrease in propagation of
synaptic impulses. It also modulated high voltage activated
calcium channels and reduces release of glutamate [10].
Oxcarbazepine may reduce efficacy of estrogen contain-
ing substances at high doses [20]. Common adverse effects
include somnolence, headache, dizziness, blurred vision,
diplopia, fatigue, nausea, vomiting, ataxia, rash and alope-
cia. Hyponatremia is seen in up to 46% of patients and is
generally asymptomatic. Rare serious rash including SJS,
TEN and erythema multiforme can be seen in about 5% of
patients. These have a strong association with the HLA-B1502
allele [10]. Hypersensitivity reactions may occur. Rare but
serious side effects also include agranulocytosis, pan-
cytopenia or aplastic anemia, arrhythmia and atrio-
ventricular block, and angioedema [10]. Oxcarbaz-
epine should be considered as first-line monotherapy
for focal seizures. It is not recommended in primary gen-
eralized epilepsies as it may exacerbate seizures in these
conditions.
Perampanel
Perampanel is FDA approved as monotherapy or adjunctive
treatment for focal seizures in patients aged 4 y or older and
as adjunctive therapy for primary generalized tonic–clonic
seizures in patients aged 12 y and older. Perampanel is an
AMPA glutamate receptor antagonist and thereby inhibits
increase in intracellular calcium and reduces neuronal excit-
ability [10, 14]. Common adverse effects include dizziness,
somnolence, headache, fatigue, ataxia and blurred vision.
Aggression and hostility may occur, particularly at higher
doses of 12 mg per day in about a fifth of patients [14].
Perampanel can enhance the metabolism of progesterone
component of hormonal contraceptives [10]. Perampanel in
USA has a boxed warning for counseling regarding severe
behavioral reaction and homicidal ideations.
997
Rufinamide
Rufinamide is FDA indicated as adjunctive treatment of sei-
zures associated with LGS in patients aged 1 y or older. Rufi-
namide binds to voltage-gated sodium channels and prolongs
their inactive state [10]. Common adverse effects include
dizziness, fatigue, somnolence, and headache. It may also
cause GI intolerance and vomiting in children [14]. Rufina-
mide may cause shortening of the QT interval [14]. Hyper-
sensitivity syndrome may also be seen [10].
Stiripentol
Stiripentol is approved for adjunctive treatment of seizures
in children aged 2 y or older with severe myoclonic epilepsy in
infancy (Dravet syndrome) who are taking clobazam [29].
Stiripentol increases brain GABA levels by inhibition of
synaptic uptake of GABA and inhibition of GABA transami-
nase. Oral bioavailability is increased with food ingestion
since stiripentol rapidly degrades in an acidic environment.
Common adverse effects include drowsiness, anorexia, loss
of appetite, nausea, vomiting, drowsiness, ataxia, dystonia
and hyperkinesias, insomnia, aggression, irritability, and
behavior disorders. Serious adverse effects include cutane-
ous photosensitivity, rash, and urticaria [10].
Tiagabine
Tiagabine selectively blocks reuptake of GABA by pre-
synaptic GABA transporter-1 [10, 29] and is approved for
adjunctive treatment of severe focal seizures that have not
responded to other antiseizure medications in individuals
aged 12 y or older [30]. It should not be used in generalized
epilepsies, particularly with absence seizures.
Topiramate
Topiramate is a broad spectrum ASM, generally used as
second line therapy for focal seizures as well as general-
ized seizures It is also used as first or second line treatment
for seizures associated with LGS. FDA indications include
monotherapy or adjunctive therapy (in individuals aged 2 y or
older) for focal or generalized tonic clonic seizures, as well
as adjunctive therapy for adult or pediatric patients aged 2 y or
older with LGS. Topiramate has multiple mechanisms of

998
actions including blocking voltage-gated sodium channels,
augmentation of GABA activity, antagonism of AMPA/
kainite receptors, inhibition of high-voltage activated cal-
cium channels and weak inhibition of carbonic anhydrase
activity [10, 20]. Common adverse effects include seda-
tion, fatigue, dizziness, ataxia, nystagmus, tremor, blurred
vision, anorexia, nausea, taste perversion, and weight loss.
Slow titration may improve tolerability. Topiramate may
cause psychomotor slowing, decreased attention, cognitive
difficulties including impairment of language and verbal
memory, slurred speech, and change in behavior and mood
[10]. Hypohydrosis, hyperthermia, and metabolic acidosis
may occur and are more common in children. Nephro-
lithiasis is seen in 1%–2% of individuals [10, 14]. Rarely
acute angle-closure glaucoma, paresthesias in hands and
feet may also occur. When used in pregnant women it is
associated with an increased risk of oral clefts in exposed
infants. Hyperammonemia, hypothermia, elevated
transaminases, and apathy may occur when topiramate is
used in conjunction with valproate [10, 20]. Topamax also
enhances metabolism of oral contraceptives.
Vigabatrin
Vigabatrin is FDA indicated for adjunctive treatment for
patients aged 10 y or older who have refractory focal seizures
and who have inadequately responded to several alternative
treatments and for whom the potential benefits outweigh
the risk of vision loss. It is also indicated as monotherapy
for pediatric patients between 1 mo and 2 y of age with
infantile spasms, particularly those with TSC, for whom
the potential benefits outweigh the potential risk of vision
loss. Vigabatrin irreversibly inhibits GABA transaminase
thereby resulting in accumulation of GABA [14]. Common
adverse effects of vigabatrin include sedation, fatigue, diz-
ziness, headache, ataxia, paresthesias, nausea, and abdomi-
nal pain [10]. Bilateral concentric visual field constriction
which is progressive and permanent may be observed in
about 30% of individuals [31]. Males have a two-fold risk
as compared to females. The risk increases with increased
dose and duration of therapy [32]. Asymptomatic and
reversible MRI changes consisting of increased T2 signal
and restricted diffusion in deep white matter, basal ganglia
and thalamus may be seen in treated infants particularly
when used with high dose ACTH [33, 34]. Rarely angi-
oedema, urticarial, hallucinations and retinal atrophy may
be seen. It may aggravate myoclonic and absence seizures
and provoke absence status epilepticus [24]. It may also
cause an encephalopathic syndrome consisting of sedation,
stupor and confusion [10]. Periodic visual assessment is
recommended at baseline and at every 3 mo.
Indian Journal of Pediatrics (October 2021) 88(10):993–999
Zonisamide
Zonisamide is approved as adjunctive therapy for treatment of
focal seizures in adolescents and adults over > 16 y of age with epi-
lepsy. In Europe and Japan it is indicated for monotherapy in
focal seizures and generalized seizures. However, it is rarely
used as a first-line agent due to its cognitive adverse effects.
Zonisamide blocks sodium channels and T-type calcium
channels, inhibits potassium mediated glutamate release,
down-regulates GABA transporter-1, and is a weak inhibitor
of carbonic anhydrase activity [10]. Common adverse effects
include sedation, ataxia, dizziness, nausea, fatigue, agitation,
irritability, hyperactivity, poor attention, dysphoria, paranoia,
anorexia, nausea, vomiting and weight loss [14]. Cognitive
slowing, impairments with verbal learning, aggression,
irritability, hyperactivity and inattention may be seen [10].
Metabolic acidosis, hypohydrosis, and hyperthermia are more
common in children [14]. Nephrolithiasis is seen in 1%–2%
of cases. Rare but serious adverse effects include SJS, TEN,
hepatic necrosis, aplastic anemia, and agranulocytosis [10].
Conclusion
The ever-expanding selection of ASMs allows more
options to select an ASM tailored to individual patient’s
comorbidities and unique characteristics. Nonetheless,
none of these medications address epileptogenesis or may
be considered “disease modifying.” Unfortunately, the
prevalence of drug-resistant epilepsy remains unchanged
despite several new ASMs.
Authors’ Contribution  SS: Design, data collection, writing; AG: Criti-
cal revisions of intellectual content. AG is the guarantor of this paper.
Declarations 
Conflict of Interest None.
References
1. French JA, Kanner AM, Bautista J, et al. Efficacy and toler-
ability of the new antiepileptic drugs, I: treatment of new-onset
epilepsy: report of the TTA and QSS subcommittees of the
American Academy of Neurology and the American Epilepsy
Society. Epilepsia. 2004;45:401–9.
2. French JA, Kanner AM, Bautista J, et al. Efficacy and toler-
ability of the new antiepileptic drugs II: treatment of refractory
epilepsy: report of the therapeutics and technology assessment
subcommittee and quality standards subcommittee of the Amer-
ican Academy of Neurology and the American Epilepsy Society.
Neurology. 2004;62:1261–73.
Indian Journal of Pediatrics (October 2021) 88(10):993–999
3. Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD
study of effectiveness of carbamazepine, gabapentin, lamotrigine,
oxcarbazepine, or topiramate for treatment of partial epilepsy: an
unblinded randomised controlled trial. Lancet. 2007;369:1000–15.
4. Epidiolex prescribing information. Available at: Epidiolex pre-
scribing information. https://w ​ ww.a​ ccess​ data.f​ da.g​ ov/d​ rugsa​ tfda_​
docs/​label/​2018/​21036​5lbl.​pdf. Accessed on 24 July 2020.
5. Krauss GL, Klein P, Brandt C, et  al. Safety and efficacy of
adjunctive cenobamate (YKP3089) in patients with uncontrolled
focal seizures: a multicentre, double-blind, randomised, placebo-
controlled, dose-response trial. Lancet Neurol. 2020;19:38–48.
6. Xcopri (cenobamate tablets) prescribing information. Available
at: https://​www.​acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​2019/​
21283​9s000​lbl.​pdf. Accessed on 10 March 2020.
7. Cenobamate prescribing information. Available at: https://​www.​
acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​2019/​21283​9s000​lbl.​
pdf. Accessed on 24 July 2020.
8. Onfi prescribing information. Available at: https://w ​ ww.a​ cces​sdata.​
fda.g​ ov/d​ rugsa​ tfda_​docs/​label/​2016/​20399​3s005​lbl.​pdf. Accessed
on 1 Feb 2020.
9. Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA;
OV-1012 Study Investigators. Randomized, phase III study
results of clobazam in Lennox-Gastaut syndrome. Neurology.
2011;77:1473–81.
10. Patsalos PN, St Louis EK. The epilepsy prescriber’s guide to
antiepileptic drugs. 3rd ed. Cambridge: Cambridge University
Press; 2018.
11. Benes J, Parada A, Figueiredo AA, et al. Anticonvulsant and
sodium channel-blocking properties of novel 10,11-dihydro-
5H-dibenz[b, f]azepine-5-carboxamide derivatives. J Med Chem.
1999;42:2582–7.
12. Sperling MR, Abou-Khalil B, Harvey J, et al. Eslicarbazepine
acetate as adjunctive therapy in patients with uncontrolled partial-
onset seizures: results of a phase III, double-blind, randomized,
placebo-controlled trial. Epilepsia. 2015;56:244–53.
13. Aptiom (eslicarbazepine acetate) prescribing information. Avail-
able at: https://​www.​acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​
2013/​02241​6s000​lbl.​pdf. Accessed on 1 Feb 2020.
14. Abou-Khalil BW. Update on antiepileptic drugs 2019. Continuum
(Minneap Minn). 2019;25:508–36.
15. Rho JM, Donevan SD, Rogawski MA. Mechanism of action of
the anticonvulsant felbamate: opposing effects on N-methyl-D-
aspartate and gamma-aminobutyric acidA receptors. Ann Neurol.
1994;35:229–34.
16. Felbamate prescribing information. Available at: https://​www.​
acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​2009/​02018​9s022​lbl.​
pdf. Accessed on 1 Feb 2020.
17. Sachdeo R, Wagner ML, Sachdeo S, et al. Coadministration
of phenytoin and felbamate: evidence of additional pheny-
toin dose-reduction requirements based on pharmacokinetics
and tolerability with increasing doses of felbamate. Epilepsia.
1999;40:1122–8.
999
18. Wagner ML, Graves NM, Leppik IE, et al. The effect of fel-
bamate on valproic acid disposition. Clin Pharmacol Ther.
1994;56:494–502.
19. St Louis EK , Patsalos PN.The epilepsy prescriber’s guide to Antie-
pileptic Drugs. Cambridge: Cambridge University Press; 2018.
20. Koubeissi MZ, Azar NJ. Epilepsy board review: a comprehensive
guide. New York: Springer; 2017.
21. Lagae L, Sullivan J, Knupp K, et al. Fenfluramine hydrochloride
for the treatment of seizures in Dravet syndrome: a randomised,
double-blind, placebo-controlled trial. Lancet. 2019;394:2243–54.
22. Nabbout R, Mistry A, Zuberi S; FAiRE, DS Study Group, et al.
Fenfluramine for treatment-resistant seizures in patients with
dravet syndrome receiving stiripentol-inclusive regimens: a ran-
domized clinical trial. JAMA Neurol. 2019;77:300–8.
23. Highlights of Fenfluramin prescribing information. Available
at: https://​www.​acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​2011/​
20208​8s001​lbl.​pdf. Accessed on 24 July 2020.
24. Perucca E, Gram L, Avanzini G, Dulac O. Antiepileptic drugs as
a cause of worsening seizures. Epilepsia. 1998;39:5–17.
25. Curia G, Biagini G, Perucca E, Avoli M. Lacosamide a new
approach to target voltage-gated sodium currents in epileptic dis-
orders. CNS Drugs. 2009;23:555–68.
26. Sake JK, Hebert D, Isojärvi J, et al. A pooled analysis of lacosa-
mide clinical trial data grouped by mechanism of action of con-
comitant antiepileptic drugs. CNS Drugs. 2010;24:1055–68.
27. Briviact (brivaracetam) prescribing information. Available at:
https://​www.​brivi​acthcp.​com/​brivi​act-​PI.​pdf. Accessed on 24
July 2020.
28. Klein P, Schiemann J, Sperling MR, et al. A randomized, double-
blind, placebo-controlled, multicenter, parallel-group study to evalu-
ate the efficacy and safety of adjunctive brivaracetam in adult patients
with uncontrolled partial-onset seizures. Epilepsia. 2015;56:1890–8.
29. Stiripental highlights of prescribing information. Available at:
https://​www.​acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​2018/​
20670​9s000​,20722​3s000​lbl.​pdf. Accessed on 24 July 2020.
30. Tiagabine prescribing information. Available at: https://​www.​
acces​sdata.​fda.​gov/​drugs​atfda_​docs/​label/​2009/​02064​6s016​lbl.​
pdf. Accessed on 24 July 2020.
31. Kälviäinen R, Nousiainen I, Mäntyjärvi M, et al. Vigabatrin,
a gabaergic antiepileptic drug, causes concentric visual field
defects. Neurology. 1999;53:922–6.
32. Toggweiler S, Wieser HG. Concentric visual field restriction
under vigabatrin therapy: extent depends on the duration of drug
intake. Seizure. 2001;10:420–3.
33. Pearl PL, Vezina LG, Saneto RP, et al. Cerebral MRI abnormalities
associated with vigabatrin therapy. Epilepsia. 2009;50:184–94.
34. Wheless JW, Carmant L, Bebin M, et al. Magnetic resonance
imaging abnormalities associated with vigabatrin in patients with
epilepsy. Epilepsia. 2009;50:195–205.
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.