Epilepsia, 54(3):393–404, 2013
doi: 10.1111/epi.12058
CRITICAL REVIEW AND INVITED COMMENTARY
Lacosamide as a new treatment option in status epilepticus
Julia H€
ofler and Eugen Trinka
Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University of Salzburg, Salzburg, Austria
SUMMARY
Status epilepticus is among the most common neurologic
emergencies, with a mortality rate of up to 20%. The most
important therapeutic goal is fast, effective, and well-
tolerated cessation of status epilepticus. Intravenous phe-
nytoin/fosphenytoin, phenobarbital, or valproate is the
current standard treatment after failure of benzodiaze-
pines. Lacosamide as a new antiepileptic drug has been
available as an intravenous solution since 2009. To date,
PubMed lists 19 studies (10 single case reports and 9 case
series), reporting a total of 136 episodes of refractory
status epilepticus (50% nonconvulsive status epilepticus,
31% focal status epilepticus, and 19% convulsive status
Status epilepticus (SE) is a life-threatening condition that
requires urgent and rigorous treatment with antiepileptic
drugs (AEDs). More than 60% of generalized convulsive
SE will be controlled by first-line treatment with intra-
venous (IV) lorazepam (LZP) (Leppik et al., 1983; Treiman
et al., 1998; Alldredge et al., 2001) or intramuscular
midazolam (MDZ) (Silbergleit et al., 2012), irrespective of
its cause. At least 40% of all patients will need further treat-
ment with IV AEDs. Despite its known disadvantages (such
as cardiac arrhythmias or hypotension), IV phenytoin
(PHE) is frequently used to control the seizures, assuming
that treatment benefits outweigh the well-known risks
(Brophy et al., 2012).
Lacosamide (LCM) became available in Europe in Sep-
tember 2009 and in the United States in October 2009 as an
IV solution based on bioequivalence to the oral formulation
(Biton et al., 2008; Krauss et al., 2010). LCM is a function-
alized amino acid with anticonvulsant properties. Its mecha-
nism of action is the selective enhancement of sodium
channel slow inactivation (Beyreuther et al., 2007). LCM
was effective in different rodent seizure models for general-
ized and complex partial seizures as well as for SE (Beyreu-
ther et al., 2007; St€
ohr et al., 2007).
Accepted October 25, 2012; Early View publication January 7, 2013.
Address correspondence to Eugen Trinka, Universit€atsklinik f€ur Neuro-
logie, Christian-Doppler-Klinik, Paracelsus Medical University, Ignaz-
Harrer-Str. 79, A-5020 Salzburg, Austria. E-mail: e.trinka@salk.at
Wiley Periodicals, Inc.
© 2013 International League Against Epilepsy
393
epilepticus) treated with lacosamide. The most often used
bolus dose was 200–400 mg over 3–5 min. The overall suc-
cess rate was 56% (76/136). Adverse events (AEs) were
reported in 25% (34/136) of patients: mild sedation in 25
cases, 1 patient with possible angioedema, 2 with allergic
skin reaction, 4 with hypotension, and 1 with pruritus. One
patient developed a third-degree atrioventricular (AV)
block and paroxysmal asystole. Overall, the rate of AEs
was low. Current evidence on the use of intravenous laco-
samide in acute seizures and status epilepticus is restricted
to retrospective case reports and case series (class IV). Fur-
ther prospective studies to inform clinicians are necessary.
KEY WORDS: Lacosamide, Acute seizures, Seizure
emergency, Treatment algorithm, Antiepileptic drug.
Based on experimental evidence (St€ohr et al., 2007;
Wasterlain et al., 2011), safety studies in healthy individuals
and patients (Ben-Menachem et al., 2007; Biton et al., 2008;
Krauss et al., 2010), as well as retrospective case series with
SE and seizure clusters in humans (Kellinghaus et al., 2009;
Tilz et al., 2010; Turpin-Fenoll et al., 2010; Albers et al.,
2011; Chen et al., 2011; Goodwin et al., 2011; Granda-
Mendez et al., 2011; H€ofler et al., 2011; Kellinghaus et al.,
2011; Koubeissi et al., 2011; Krause et al., 2011; LaRoche
& Shivdat-Nanhoe, 2011; Parkerson et al., 2011; Rantsch
et al., 2011; Shiloh-Malawsky et al., 2011; Torres-Cano
et al., 2011; Cherry et al., 2012; Jain & Harvey, 2012; Mnat-
sakanyan et al., 2012), IV LCM may be a useful alternative
in emergency treatment of seizures with IV AEDs.
The aim of the present review is to analyze all published
studies on IV LCM in the treatment of SE and acute recur-
rent seizures.
Methods
Identification of studies and search strategy
All 19 studies were identified by electronic search of Pub-
Med (January 2009–May 2012) using the search terms:
“lacosamide” AND “intravenous” AND “status epilepti-
cus.” Only studies published as a full article were eligible if
they reported the use of IV LCM in the treatment of SE.
Mechanism of action of LCM
LCM is a functionalized amino acid with anticonvulsive
properties (Andurkar et al., 1999; Hovinga, 2003; Duncan &
394
J. H€
ofler and E. Trinka
Kohn, 2005). LCM selectively enhances slow inactivation of
sodium channels, with no effect on fast inactivation (Erring-
ton et al., 2006). This mechanism is in contrast to other AEDs
such as carbamazepine (CBZ) or PHE, which do not enhance
slow inactivation. LCM shifts the voltage dependence of
inactivation to more hyperpolarized membrane potentials and
thereby promotes the transition of sodium channels into the
slow inactivated state (Beyreuther et al., 2007).
Pharmacokinetics of LCM
Oral LCM is rapidly absorbed, and plasma concentra-
tions are dose proportional. With an elimination half-life of
13 h, a twice-daily dosing is possible. Steady state is
reached within 2–3 days (Horstmann et al., 2002; Hovinga,
2003; Cawello et al., 2004). LCM has a low protein binding
(<15% bound) and no effect on the plasma concentrations
of concomitantly administered AEDs (Kropeit et al., 2004;
Jatuzis et al., 2005). A small proportion of LCM is metabo-
lized to an O-desmethyl metabolite that is not pharmacolog-
ically active in in vivo models (Doty et al., 2007; Cross &
Curran, 2009). LCM and its major metabolites are elimi-
nated renally.
Because of its high water solubility, LCM was also devel-
oped as an IV solution, in parallel with the oral formula-
tions. The isotonic solution contains 10 mg/ml and has a pH
of 3.5–5. The solution is stable at room temperature and can
be administered without dilution (Biton et al., 2008).
However, it can also be diluted in sodium chloride 0.9%,
dextrose 5%, or lactated Ringers solution, if needed. In a
phase 1 trial with 24 healthy volunteers, bioequivalence of
short-time infusion was demonstrated as a replacement ther-
apy for oral LCM at doses of 200 mg twice daily and IV
infusions at 30 and 60 min (Kropeit et al., 2004).
Krauss et al. (2010) reported a multicenter, open-label,
inpatient, dose-escalation trial with 160 patients from ongo-
ing open-label, long-term trials who were taking stable
doses of oral LCM and up to three concomitant AEDs. The
patients received IV LCM dosed over progressively shorter
infusion durations: 30, 15, and 10 min for 2–5 days. Most
patients received IV LCM 200–600 mg/day; around 4% (7/
160) received 700–800 mg/day in 15 min.
The adverse event (AE) rate was low, the most common
(10% or less) being headache, dizziness, diplopia, and som-
nolence. The occurrence of AEs did not correlate with
shorter infusion time, but with higher doses of LCM. Two
patients had cardiac AEs: one patient treated with beta-
blockers had a reversible bradycardia of 26 bpm during a
15-min infusion on day 2 of treatment with 300 mg/day IV
LCM; the second patient had a nonrecurring prolonged
QTcB interval, without clinical symptoms or signs, on day 4
of treatment with 100 mg/day IV LCM by 15-min infusion.
It should be noted that all patients were long-term respond-
ers to LCM in the open-label extension trials, which
enriches the study population with those patients who toler-
ate LCM well (Krauss et al., 2010).
Epilepsia, 54(3):393–404, 2013
doi: 10.1111/epi.12058
Another multicenter double-blind, double-dummy, ran-
domized, inpatient trial supported the safety and utility of
IV LCM as replacement for oral LCM. Intravenous LCM
was administered as 60- or 30-min twice-daily infusions
and showed a safety and tolerability profile similar to that of
oral LCM. Treatment-emergent AEs were reported by 16 of
60 patients—including dizziness, headache, back pain, som-
nolence, and injection-site pain. All AEs were considered
mild or moderate in intensity, and no AE led to discontinua-
tion (Biton et al., 2008).
In a safety and tolerability trial with 25 subjects, IV LCM
was applied in three progressively increasing doses (200,
300, and 400 mg). Optimal tolerance was found with IV
loading doses of 200 and 300 mg administered over
15 min; a higher frequency of dose-related AEs (dizziness,
somnolence, nausea, and diplopia) was observed with a
loading dose of 400 mg (Fountain et al., 2011).
Experimental basis for the use of LCM in SE
In an experimental model of limbic self-sustaining SE
induced by perforant path stimulation, rats were treated with
IV LCM (3, 10, 30, or 50 mg/kg) either after 10 min (early)
or after 40 min (late). Compared with the late treatment,
LCM given after 10 min showed a significant dose-dependent
reduction of acute SE seizure activity (Wasterlain et al.,
2011). In other models, such as maximal electroshock test
in mice, LCM protected mice and rats against tonic-
extension seizures and prevented seizure spread (Swinyard
et al., 1952; Borowicz et al., 1997). In the 6-Hz psychomo-
tor seizure test, LCM demonstrated full efficacy in contrast
to other AEDs such as LTG, PHE, and CBZ (Barton et al.,
2001). However, LCM was not effective in chemoconvul-
sant-induced seizures induced by the subcutaneous bolus
injection of pentylenetetrazole (St€ohr et al., 2007).
Clinical studies in SE
There are 19 published articles on the use of IV LCM in
SE and acute repetitive seizures, including 10 single case
reports (Kellinghaus et al., 2009; Tilz et al., 2010; Turpin-
Fenoll et al., 2010; Chen et al., 2011; Granda-Mendez
et al., 2011; Krause et al., 2011; LaRoche & Shivdat-
Nanhoe, 2011; Parkerson et al., 2011; Shiloh-Malawsky
et al., 2011; Torres-Cano et al., 2011; see Table 1) and 9
retrospective case series (Albers et al., 2011; Goodwin
et al., 2011; H€ofler et al., 2011; Kellinghaus et al., 2011;
Koubeissi et al., 2011; Rantsch et al., 2011; Cherry et al.,
2012; Jain & Harvey, 2012; Mnatsakanyan et al., 2012; see
Table 2).
Single case reports
Kellinghaus et al. (2009) published a case of a 42-
year-old woman who had preexisting epilepsy after a severe
cardioembolic stroke in the territory of the left middle cere-
bral artery in 1993. After SE in 2006 with vomiting, worsen-
ing of her preexisting aphasia, hemiparesis, and nystagmus,
 Table 1. Overview of all case reports of SE treated with IV LCM
Why? Indication? When? Conditions? How?
Time from
SE onset to
SE specific AEDs before Order LCM LCM LCM Adverse
Study SE (n) Age (y) SE type SE etiology etiology LCM (mg) BDZ of LCM initiation dose route Outcome events
Kellinghaus 1 42 NCSE Remote Stroke IV DZP (2.5); Y 3rd  1.5 h 200 mg IV Responder Possible skin
et al. symptomatic IV LZP (6) (within after 5 itching and
(2009) 3–5 min) min mild
erythema
Tilz et al. 1 38 CSE Remote Perinatal hypoxia IV DZP (22.5); Y 6th (with Not 300 mg PEG- Responder N
(2010) symptomatic with resulting IV etomidate (12.5); etomidate) reported tube after 30
infantile cerebral IV MDZ (5); enteral (Syrup) min
palsy LZP (4); enteral LEV
(1,500)
Turpin-Fenoll 1 72 NCSE Remote Stroke LEV (3,000), VPA, Y 5th Not 25 mg PO Responder N
et al. (2010) symptomatic CLN, OXC (dose reported twice daily 1 week
and route not after
reported) LCM
was
started
Parkerson 17 75 Focal SE Remote GBM Not reported Y Not Not 100 mg IV Responder N
et al. (2011) symptomatic reported reported twice daily
Chen et al. 1 57 Focal SE/EPC Remote Traumatic LZP (2); FOS (1,000); Y 4th 4 days 50 mg PO Responder N
(2011) symptomatic brain injury LEV (3,000); LZP (2); twice per
VPA (loading day for 5
20 mg/kg, maintain days, then
10 mg/kg every 6 h); uptitration
LEV daily dose to 400
increased to mg/day
4,000 mg, PHE within
administration 8 days
within a serum level
of 20–30 lg/ml
Krause et al. 1 89 NCSE Acute Not reported IV LZP (2); Day 1: Y 3rd Not Two 400-mg IV Responder Third-degree
(2011) symptomatic IV LEV (2,000) reported bolus AV block
Day 2: IV LEV doses and asystolia
(3,000) within 6 h
Granda- 1 81 NCSE Acute Stroke IV CLN (2); IV VPA Y 3rd Not 100 mg/day IV Responder N
Mendez symptomatic (40 mg/kg) and VPA reported
et al. (2011) 800 mg/day over
continuous infusion

Continued
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doi: 10.1111/epi.12058
 396
J. H€

doi: 10.1111/epi.12058
Epilepsia, 54(3):393–404, 2013
Table 1. Continued.
ofler and E. Trinka

Why? Indication? When? Conditions? How?

Time from
SE onset to
SE specific AEDs before Order LCM LCM LCM Adverse
Study SE (n) Age (y) SE type SE etiology etiology LCM (mg) BDZ of LCM initiation dose route Outcome events
LaRoche & 1 61 NCSE Acute SESA LZP; FOS; VPA; Y 4th Not Not IV Responder N
Shivdat- symptomatic doses not reported reported reported
Nanhoe
(2011)
Torres- 1 49 NCSE Remote Polymicrogyria DZP (5); VPA Y 7th 15 days 200 mg/12 h IV Responder N
Cano symptomatic and nodular (500 + 500 mg/12 h);
et al. heterotopia LEV (1,000);
(2011) CLN (1 g/12 h);
LTG (200 mg/2 h);
propofol and MDZ
per perfusor; PHE
Shiloh- 1 8 CSE?NCSE Acute Unclear LZP; PHE; PB; VPA; Y 8th 10 weeks 25 mg Enteral Responder; N
Malawsky symptomatic LEV; FBM; TPM; twice 5 days
et al. (2011) propofol; daily after
corticosteroids; IVIG; LCM
plasmapheresis was
started,
SE was
resolved

AED, antiepileptic drug; BDZ, benzodiazepines; CLN, clonazepam; CSE, convulsive status epilepticus; DZP, diazepam; EPC, epilepsia partialis continua; FBM, felbamate; FOS, fosphenytoin; GBM, glioblastoma multi-
forme; IV, intravenous; IVIG, intravenous immunoglobulin; LCM, lacosamide; LEV, levetiracetam; LTG, lamotrigine; LZP, lorazepam; MDZ, midazolam; NCSE, nonconvulsive status epilepticus; OXC, oxcarbazepine; PB,
phenobarbital; PEG tube, Percutaneous gastrostomy tube; PHE, phenytoin; PO, orally; RSE, resistant status epilepticus; SE, status epilepticus; SESA, subacute encephalopathy and seizures in alcoholics; TPM, topiramate;
VPA, valproic acid.
 Table 2. Overview of all case series of SE treated with IV LCM
Why? Indication? When? Conditions? HOW?

Time from
Episodes SE onset to
Episodes of SE SE etiology, SE specific AEDs before BDZ, Order LCM LCM dose LCM Outcome, Adverse
Study of SE (n) Age (y) by type (n) % (n) pts etiology, n/N LCM, % (n) pts % (n) pts of LCM initiation (mg) route % (n) events (n)

Kellinghaus 39 Median 62 6 CSE 26% (10/39) Acute Not reported 95% (37/39) 95% (37/39) 13% (5/39) Median latency Median bolus IV 100% (5/5) LCM as 1 Allergic skin
et al. (2011) (range, 16 NCSE symptomatic; BDZ; 85% (33/39) pts LCM 30 (range, dose 400 1st/2nd; 95% reaction; 25
18–90) 17 focal SE 23% (9/39) LEV; 36% (14/39) as 1st/2nd; 0.5–1,440) h (range, (18/19) LCM as Sedation; 4
Remote PHE 13% (5/39) 49% (19/39) 200–400; 3rd; 73%(11/15) Hypotension
symptomatic other AEDs; 10% pts LCM as mean dose LCM as 4th/later
(new-onset (4/39) Anesthesia 3rd; 38% 1st day 424
epilepsy); (15/39) (range,
49% (19/39) pts LCM 200–600)
Remote as 4th/later
symptomatic
(preexisting
epilepsy);
3% (1/39)
Others/NK
Koubeissi 4 Median 65 4/4 NCSE 75% (3/4) Acute 2/4 Hemorrhage 100% (4/4) LZP; 50% 100% (4/4) Median4 Median 34 Median initial IV 100% (4/4) N
et al. (2011) (range, symptomatic; 1/4 Meningioma (2/4) FOS; 100% (range, 3–5) (range, dose 100 (range,
53–79) 25% (1/4) 1/4 Temporal (4/4) LEV; 25% 3–50) h 50–100)
Preexisting encephalomalacia (1/4) PGB; 25%
epilepsy (1/4) VPA
Goodwin 9 Median 63 6/9 NCSE 4 Preexisting 2/9 rapid 100% (9/9) LEV, 100% (9/9) Median 3 Median 2 Median loading IV 100% (9/9) 2 Episodes of
et al. (2011) (range, 3/9 epilepsy neurodegenerative 78% (7/9) PHE, (range, 2–5) (range, dose 200 (range, Nonresponder angioedema;
47–89) CSE 5 Acute disease; 1/9 Rosai– 22% (2/9) 0–14) days 100–300)
symptomatic Dorfman disease; Pentobarbital coma
1/9 GBM and stroke;
1/9 Aneurysms;
1/9 Stroke;
1/9 Meningioma;
1/9 VPS infection;
1/9 No underlying
neurologic disease
Albers et al. 7 Median 63 7/7 focal SE 42% (3/7) Acute 3/7 SDH; 1/7 History 29% (2/7) VPA; 42% (3/7) Median 4 Not Median initial IV 100% (7/7) N
(2011) (range, symptomatic; of stroke; 1/7 100% (7/7) (range, 2–5) reported dose 400 Responder
33–83) 29% (2/7) Alcohol abuse and LEV; 4/7 propofol; (range, 400)
Remote hypertension; 14% (1/7) PHE;
symptomatic; 1/7 ICH; 1/7 42% (3/7) TPM;
29% (2/7) Infantile 42% (3/7) MDZ
Pre-existing brain damage
epilepsy

Continued
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397

doi: 10.1111/epi.12058
 398
J. H€

Table 2. Continued.
Why? Indication? When? Conditions? HOW?

Time from

doi: 10.1111/epi.12058
Episodes SE onset to
Episodes of SE SE etiology, SE specific AEDs before BDZ, Order LCM LCM dose LCM Outcome, Adverse

Epilepsia, 54(3):393–404, 2013

Study of SE (n) Age (y) by type (n) % (n) pts etiology, n/N LCM, % (n) pts % (n) pts of LCM initiation (mg) route % (n) events (n)
ofler and E. Trinka

H€
ofler et al. 31 Median 67 11/31 CSE; 19% (6/31) Acute 1/31 NK; 5/31 68% (21/31) LEV; 94% (29/31) 7% (2/31) Not listed Median 200 IV Overall In group SE no
(2011) (range, 10/31 symptomatic; Traumatic 94% (29/31) BDZ; pts LCM (range, 81% AEs
22–95) NCSE; 35% (11/31) lesions; 1/31 10% (3/31) PHE; 1st; 19% 200–400) (25/31)
10/31 Remote Cortical dysplasia; 16% (5/31) VPA; (6/31) pts Responders
focal SE symptomatic; 9/31 Vascular 3% (1/31) LCM 2nd; LCM 1st 2/2,
46% (14/31) lesions; 3/31 Anesthesia 48% (15/31) LCM 2nd 6/6,
Preexisting Tumor; 1/31 pts LCM 3rd; LCM 3rd
epilepsy Encephalitis, 26% (8/31) 11/15, LCM
11/31 Others pts LCM 4th or
4th or later later 6/8
Cherry et al. 13 Median 51.1 7/13 NCSE; 9/13 Preexisting Not reported 92% (12/13) LZP; 92% (12/13) Mean 3.2 Mean 39.5 Mean 180.8 IV 38% (5/13) 3/13 Episodes
(2012) (range, 4/13 epilepsy 85%(11/13) (range, 1–7) (range (range, Complete of significant
24–80) focal SE; LEV; 69% (9/13) 6.5–74) h 100–400); seizure hypotension;
2/13 FOS; 31% (4/13) Infusion rate, cessation; 54% 1/13 Fever
CSE VPA; 31% mean 3.33 (7/13)  50% without
(4/13) PB (range, Reduction source;
1.67–6.67) in seizure 1/13 Elevated
mg/min frequency liver function
tests
Jain & Harvey 3 Median 16 3/3 refractory 3/3 Pre-existing 1/3 Lissencephaly; 3/3 LEV; 2/3 VPA; 100% (3/3) Median 6 Median Median 100 IV 100% (3/3) 1/3 Chorea; 1/3
(2012) (range, tonic SE epilepsy 1/3 Rett syndrome; 3/3 CLZ; 1/3 PB (range, 5–7) 28 (range, (range, 50–200) Oculogyric
12–17) 1/3 Generalized 8–29) h crisis
epilepsy
Mnatsakanyan 10 Median 60.5 10/10 NCSE 60% (6/10) 1/10 NK; 2/10 40% (4/10) BDZ; 40% (4/10) Median 4 Not Median loading IV 70% (7/10) N
et al. (2012) (range, Acute Asystole; 2/10 80% (8/8) PHE; (range, 2–8) reported dose 200–300 Responder
16–90) symptomatic; Tumor; 1/10 HSV 90% (9/10) LEV; within 30 min
40% (4/10) encephalitis; 30% (3/10) VPA;
Preexisting 1/10 Frontal 10% (1/10)
epilepsy AVM resection; Propofol
1/10 Metastases;
1/10 Stroke;
1/10 Posterior
reversible
encephalopathy
syndrome

AED, antiepileptic drug; AVM, arteriovenous malformation; BDZ, benzodiazepines; CLN, clonazepam; CSE, convulsive status epilepticus; EPC, epilepsia partialis continua; FOS, fosphenytoin; GBM, glioblastoma multi-
forme; HSV, herpes simplex virus; ICH, intracerebral hemorrhage; LCM, lacosamide; LEV, levetiracetam; LZP, lorazepam; MDZ, midazolam; NCSE, nonconvulsive status epilepticus; NK, not known; PB, phenobarbital;
PGB, pregabalin; PHE, phenytoin; SDH, subdural hematoma; SE, status epilepticus; TPM, topiramate; VPA, valproic acid; VPS, ventriculoperitoneal shunt.

she received levetiracetam (LEV) 2,000 mg/day. Under this
therapy, she developed psychotic symptoms; therapy was
therefore changed, first to lamotrigine (LTG) and then to
gabapentin (GBP). Due to noncompliance with AED dos-
ing, four further episodes of SE followed. In October 2008,
the patient had her sixth SE with her habitual clinical semi-
ology. Previous medication was LTG 200 mg and GBP
1,200 mg/day. In the emergency situation, she received IV
diazepam (DZP) 2.5 mg. Because of rhythmic slowing and
spiking on the left posterior temporal area, IV LZP 6 mg
was administered, but without success, and the patient
developed respiratory problems. Because of the enzyme-
inducing effect of valproic acid (VPA) and previous treat-
ment with LTG, VPA was not used; LEV was also avoided,
because of her previous psychiatric episode. Instead, IV
LCM was administered as a bolus of 200 mg within 3–
5 min; epileptic activity on electroencephalography (EEG)
ceased about 5 min later. After 6 days, the patient devel-
oped mild pruritus.
Tilz et al. (2010) described a 38-year-old man who had
preexisting epilepsy with infantile cerebral palsy. Diagnosis
on admission was a series of complex partial seizures, which
evolved into generalized tonic–clonic SE. PHE and VPA
had been ineffective in the past. Initially, the patient
received IV DZP 22.5 mg, IV etomidate 12.5 mg, and IV
MDZ 5 mg within 45 min. Because of ongoing SE, LZP
4 mg and LEV 1,500 mg were administered via percutane-
ous gastric fistula within 30 min. Because of the persistent
SE, treatment with a 150-mg LCM minced tablet powder
was given via percutaneous gastrostomy tube, following
which the seizures were interrupted; a second dose of
150 mg LCM syrup stopped SE after 30 min. Lower doses
of AEDs were used because of the patients low body
weight.
Turpin-Fenoll et al. (2010) presented a 72-year-old
patient with a nonconvulsive SE (NCSE) 2 weeks after his
first tonic–clonic seizure. As PHE had previously caused
bradycardia and respiratory failure, it was avoided as first-
line therapy. The patient received IV LCM after failed ther-
apy with LEV (3,000 mg/day), oxcarbazepine, VPA, and
clobazam. One week after NCSE had started, the seizures
were stopped with a dose of LCM 50 mg/day. Because of
the low dose of LCM, the authors discussed a remote effect
of previously given drugs.
Parkerson et al. (2011) reported on 17 patients who
received LCM (13 intravenously) who were undergoing
prolonged video-EEG monitoring. Three patients had no
seizures, but periodic lateralized epileptiform discharges
plus (PLEDs-plus) or generalized periodic discharges. Nine
patients had repetitive focal seizures and EEG changes (like
PLEDs or PLEDs-plus). One 75-year-old male patient had
focal SE resulting from a glioblastoma multiforme and was
taking LEV and PHE at admission. He received a benzodi-
azepine as first-line therapy, then IV LCM 200 mg/day, and
the focal SE was stopped. There were no AEs reported; in
399
IV Lacosamide in Seizure Emergencies
particular, no change of PR intervals prior to LCM or at the
end of infusion.
Chen et al. (2011) reported a patient with epilepsia parti-
alis continua: a 57-year-old man with right-sided hemipare-
sis with cognitive and language impairment after a brain
injury at age 25, who was admitted because of involuntary
jerking of the right arm and leg. EEG showed a continuous
left posterior slowing and epileptiform rhythms, with hyper-
intense areas in diffusion-weighted imaging and fluid-
attenuated inversion recovery (FLAIR) sequences observed
on magnetic resonance imaging (MRI). The patient received
IV LZP 2 mg, IV fosphenytoin (FOS) 1,000 mg, and IV
LEV 3,000 mg, but clinical status and EEG remained
unchanged. Furthermore, IV LZP 2 mg, IV VPA (loading
dose 20 mg/kg), increase of IV LEV daily dose from 3,000
to 4,000 mg, and PHE administration within a serum level
of 20–30 lg/ml achieved no seizure control. After 4 days of
refractory SE, an oral dose of LCM 100 mg/day was started
and all other AEDs except LEV were tapered down. On day
4, the SE was stopped clinically and electrographically. This
low dose of LCM was claimed to be effective, but of course
SE may have resolved unrelated to LCM.
Krause et al. (2011) described an 89-year-old woman
who was admitted to the hospital with an NCSE. She had a
history of arterial hypertension, heart insufficiency, and
hypothyroidism, and had been treated with a beta-blocker
and amlodipine. Laboratory tests showed a potassium level
of 2.5 mEq/L, so supplementation was started. For SE, the
patient initially received IV LZP 2 mg; SE continued, and
she developed respiratory problems. On day 1, IV LEV
2,000 mg was administered as a bolus within 60 min, fol-
lowed by 3,000 mg on day 2. Because of persistent SE, IV
LCM was administered in two 400-mg bolus doses within
6 h, following which the patient developed third-degree AV
block and asystole three times, with duration of  10 s.
After infusion 30 min later with 500 ml hydroxyethyl
starch, sinus rhythm with first-degree AV block returned;
the PQ interval normalized over the course of the next day.
Possible reasons for the occurrence of AV block included
the low potassium level, negative effects of premedication
on AV conduction, and the low glomerular filtration rate.
The authors concluded that high doses of LCM should be
avoided in patients at risk for AV conduction delay.
One 61-year-old patient with NCSE during the course of
subacute encephalopathy with seizures was fully controlled
by IV LCM after failure of LZP, FOS, and VPA. Dose and
duration of SE before LCM were not reported. No AEs were
noted (LaRoche & Shivdat-Nanhoe, 2011).
Shiloh-Malawsky et al. (2011) reported an 8-year-old
boy with convulsive seizures 2 days after a febrile illness.
Because of frequent focal seizures, he received PHE, pheno-
barbital (PB), VPA, and LEV, but without success; thus he
had up to 300 focal-onset electrographic seizures per
day under a combination of six AEDs (PHE, LEV, PB,
topiramate [TPM], felbamate [FBM], and VPA). He also
Epilepsia, 54(3):393–404, 2013
doi: 10.1111/epi.12058
400
J. H€
ofler and E. Trinka
received propofol, pentobarbital, MDZ, and ketamine, until
a burst-suppression EEG pattern, for up to 1 week and a ke-
togenic diet for 6 weeks. Doses for AEDs and anesthetics
were not reported. Because of a possible autoimmune etiol-
ogy, the patient was treated with high-dose corticosteroids,
IV immunoglobulin, and plasmapheresis, but again without
effect. Ten weeks after refractory SE (RSE), LCM 25 mg
was administered enterally twice daily; seizure frequency
decreased significantly within 3 days, with seizures ceasing
altogether after 5 days. It is possible that the response after
3 days of therapy with low dose LCM may have been noth-
ing to do with the LCM.
Granda-Mendez et al. (2011) presented the case of an 81-
year-old woman with an acute symptomatic SE after an
ischemic infarction of the left/right posterior cerebral artery.
Initially she received IV clonazepam (CLN) 2 mg, followed
by IV VPA at a dose of 40 mg/kg, and then 800 mg/day
continuous infusion. Because of comorbidities (chronic
renal failure), PHE and LEV were avoided and the patient
received IV LCM 100 mg/day. No AEs were reported.
Torres-Cano et al. (2011) reported a 49-year-old woman
with an NCSE. She had symptomatic epilepsy due to poly-
microgyria and nodular heterotopia. The premedication was
VPA 500 mg twice daily, CLN 1 mg twice daily, and LEV
500 mg twice daily. In the emergency department she
received IV DZP 5 mg, IV VPA 500 mg, and IV LEV
500 mg before being admitted to the intensive care unit,
where she received another IV LEV 500 mg over 12 h, IV
CLN (1 g/12 h), and IV VPA (500 mg/12 h). Because of
generalized convulsions, the patient received propofol and
MDZ by perfusor. After 10 days, the SE persisted; treat-
ment was IV CLN 1 g/12 h, IV LTG 200 mg/12 h, and
PHE. On day 15, IV LCM 200 mg/12 h was added, and SE
resolved at day 17.
Retrospective case series
Kellinghaus et al. (2011) reported the pooled experience
of four centers in Germany, Austria, and Switzerland. Alto-
gether, 39 patients receiving IV LEV for the treatment of
SE (six convulsive SE [CSE], 17 NCSE, and 16 focal SE)
refractory to benzodiazepines were included. Acute symp-
tomatic etiology was found in 10 patients (26%), remote
symptomatic in 9 (23%), and preexisting epilepsy in 19
(49%). Specific etiologies were not reported for individual
patients. LCM was successfully used as first or second
drug in 3 of 5 patients, as third drug in 11 of 19 patients,
and as fourth or later drug in 3 of 15 patients. Median bolus
dose was 400 mg (range 200–400). In 44% of patients
(17/39), SE was controlled by LCM; only mild AEs were
reported (1 allergic skin reaction, 25 sedation, 4 hypoten-
sion). Of the 39 patients, 37 received benzodiazepines as
first-line treatment. When LCM was administered early (as
first, second, or third drug) it was successful in 60%,
whereas only 20% were treated successfully in later stages
of SE.
Epilepsia, 54(3):393–404, 2013
doi: 10.1111/epi.12058
Rantsch et al. (2011) reported on nine patients with 10
episodes of SE (eight NCSE and two focal SE). The etiol-
ogy was remote in six patients, and acute symptomatic in
three. Median administration of LCM was as the sixth drug
(range 4th–12th), with an initial dose of 50–100 mg. In 2
(20%) of 10 episodes of SE, LCM was the last drug. AEs
were not reported. Three patients died during the observa-
tion period due to complications of their underlying dis-
ease. In this study, the investigators found a highly
significant (r = 0.94, p < 0.00005) correlation between age
and outcome: patients aged <60 years returned to baseline,
whereas those aged >75 years died. However, this is an
uncontrolled small series and these data must be interpreted
with caution.
Goodwin et al. (2011) described nine patients with RSE,
which was defined as seizure lasting >30 min, or multiple
seizures without return of consciousness, and a failure of at
least two medications to abort SE. Six of their patients had
NCSE; three had CSE. Four had a preexisting epilepsy and
five were acute symptomatic. Patients had three (range 2–5)
AEDs prior to LCM, and all received benzodiazepines as
first-line treatment. Response to LCM was defined for the
patients in burst suppression as an absence of electrographic
seizure activity for 24 h; for patients not in burst suppres-
sion, response was defined as electrographic seizure resolu-
tion  4 h after LCM administration. None of their patients
had their SE controlled with IV LCM, and only one patient
had an improvement of his EEG, without clinical improve-
ment. Two patients had a decrease of seizure frequency with
PHE and LCM. Two patients died during the observation
period due to their underlying disease. The median initial
dose was 200 mg (range 100–300). Two patients had an-
gioedema during LCM treatment.
Koubeissi et al. (2011) reported on four patients with
NCSE. Etiology was acute symptomatic in three patients;
one had a preexisting epilepsy. One patient had a temporal
encephalomalacia, one had a meningioma, and two had an
intracerebral hemorrhage; they all received benzodiaze-
pines as first-line drugs. LCM was on median the fourth
AED (range 3rd–5th) and the initial dose was in the range of
50–100 mg. All patients were responders and no AEs were
observed. Positive response or “seizure freedom” was
defined as a reduction of seizure frequency from two to
three seizures per hour to one seizure every 2 h.
Another retrospective study (Albers et al., 2011)
described seven patients treated with IV LCM for focal SE.
Three had acute symptomatic, two remote symptomatic,
and two a preexisting epilepsy. Three patients had intracere-
bral subdural hematomas; one had a history of ischemic
stroke, one patient a history of infantile brain damage, and
one patient a history of intracerebral bleeding. One patient
had alcohol abuse and hypertension. LCM was used on
median as fourth drug (range 2nd–5th). Initial loading was
400 mg/day. Response to LCM was defined as resolution of
EEG status within 24 h. In all patients, SE was resolved and

no serious AEs were reported. Four of the seven patients
had no initial treatment with benzodiazepines, whereas one
received this only during the course of treatment.
Cherry et al. (2012) reported on 24 patients: 10 with 13
episodes of RSE (defined as SE with failed response to
 2 drugs), and 14 with isolated seizures. Specific etiolo-
gies for SE were not reported in detail. Among 13 episodes
of RSE, 7 were nonconvulsive, 4 focal, and 2 convulsive.
The median use of LCM was as third drug (range 1st–7th).
Concurrent AEDs were LZP in 92% (12/13), LEV in 85%
(11/13), FOS in 69% (9/13), VPA in 31% (4/13), PB in
22% (6/13), “other” in 19% (5/13), and sedatives or anes-
thetics in 33% (9/13). Complete seizure cessation was
achieved in 5 of 13 episodes (38%) of SE, and seizure
reduction of >50% in 7 of 13 episodes (54%). The median
loading dose was 180.8 mg (range 100–400 mg) and mean
maintenance dose 361.5 mg/day. Three episodes of signifi-
cant hypotension, and one fever with unknown origin, were
observed. One patient had elevated liver function test lead-
ing to discontinuation of LCM.
Our own group (H€ ofler et al., 2011) reported on 48
patients: 17 (35%) with seizure clusters (SCs) and 31 (65%)
with SE. The etiology was acute symptomatic in six (19%)
and remote symptomatic in 11 (36%) patients, whereas 14
patients (45%) had a preexisting epilepsy. Altogether, 32%
had NCSE, 36% had a convulsive, and 32% had a focal SE.
Median initial bolus dose was 200 mg (range 200–400 mg).
LCM was used as first drug in two patients (7%); in both,
SE was controlled. In six patients (19%), LCM was used as
second drug; again, all of these patients responded. In 15
patients (48%), LCM was administered as the third drug,
and in 11 (73%) of these SE was stopped. Eight patients
(26%) received LCM as fourth or later drug, and six of these
(75%) were responders. Overall, we observed cessation of
SE in 81% (25/31). No serious AEs were identified.
Mnatsakanyan et al. (2012) identified 10 patients with
NCSE, of whom 6 had an acute symptomatic SE. Specific
etiologies were found in 9 of 10 patients: glioma resection,
herpes simplex virus encephalitis, frontal arteriovenous
malformation, multifocal glioma, brain metastases, stroke,
posterior reversible encephalopathy syndrome, and anoxic
brain injury due to asystole. The median use of LCM was as
fifth drug (range 3rd–9th), including initial treatment with
LZP. The median loading dose was 200–300 mg within
30 min, with a maintenance dose in the range of 100–
200 mg every 12 h. SE resolved in seven patients; AEs
were not reported. In two of three nonresponders, the spe-
cific etiology was anoxic brain injury.
Jain & Harvey (2012) described three patients (ages 12–17
years) with symptomatic generalized epilepsy with intel-
lectual disability and refractory tonic SE. LCM bolus doses
(2–2.5 mg/kg; 50–200 mg in the first 2 h) were used after
three or more standard AEDs had been ineffective. In two
patients, side effects were reported (chorea and oculogyric
crisis). Duration of SE prior to LCM was 8–29 h. In two
401
IV Lacosamide in Seizure Emergencies
patients, there was an immediate clinical response to LCM;
the other had resolution of SE after the second dose.
Route of Administration of LCM
Single case reports
The route of administration was oral in one patient (Chen
et al., 2011), enteral in three (Tilz et al., 2010; Turpin-
Fenoll et al., 2010; Shiloh-Malawsky et al., 2011), and IV
in the remaining six patients (Granda-Mendez et al., 2011;
Kellinghaus et al., 2011; Krause et al., 2011; LaRoche &
Shivdat-Nanhoe, 2011; Parkerson et al., 2011; Torres-Cano
et al., 2011).
Case series
We divided the case series into two subgroups, according
to the number of included patients: Group I included all
studies with a study population of 3–29 patients (Albers
et al., 2011; Goodwin et al., 2011; Koubeissi et al., 2011;
Rantsch et al., 2011; Cherry et al., 2012; Jain & Harvey,
2012; Mnatsakanyan et al., 2012), whereas Group II
included studies with >30 patients (H€ofler et al., 2011;
Kellinghaus et al., 2011).
In both groups, all episodes (126/126) of SE were treated
with IV LCM (Albers et al., 2011; Goodwin et al., 2011;
H€ofler et al., 2011; Kellinghaus et al., 2011; Koubeissi
et al., 2011; Rantsch et al., 2011; Cherry et al., 2012; Jain
& Harvey, 2012; Mnatsakanyan et al., 2012).
Type and Outcome of SE; Dose
and Order of LCM
Single case reports
Seven of 10 reported SE were NCSE (Kellinghaus et al.,
2009; Turpin-Fenoll et al., 2010; Granda-Mendez et al.,
2011; Krause et al., 2011; LaRoche & Shivdat-Nanhoe,
2011; Shiloh-Malawsky et al., 2011; Torres-Cano et al.,
2011), one a CSE (Tilz et al., 2010), and two a focal SE
(Chen et al., 2011; Parkerson et al., 2011). All 10 SE
reported by single case reports stopped after LCM treatment
(Kellinghaus et al., 2009; Tilz et al., 2010; Turpin-Fenoll
et al., 2010; Chen et al., 2011; Granda-Mendez et al., 2011;
Krause et al., 2011; LaRoche & Shivdat-Nanhoe, 2011;
Parkerson et al., 2011; Shiloh-Malawsky et al., 2011; Tor-
res-Cano et al., 2011). In one of 10 case reports, the initial
dose was not specified (LaRoche & Shivdat-Nanhoe, 2011);
the median initial dose of the other nine case reports was
100 mg (range 50–400 mg). The lowest doses of 25 mg
twice daily were applied by enteral route for a 72-year-old
patient and an 8-year-old patient (Turpin-Fenoll et al.,
2010; Shiloh-Malawsky et al., 2011).
Order of LCM in the treatment algorithm: median use of
LCM was as fourth drug (range 2nd–8th) (Kellinghaus
et al., 2009; Tilz et al., 2010; Turpin-Fenoll et al., 2010;
Chen et al., 2011; Granda-Mendez et al., 2011; Krause
Epilepsia, 54(3):393–404, 2013
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402
J. H€
ofler and E. Trinka
et al., 2011; Shiloh-Malawsky et al., 2011; Torres-Cano
et al., 2011). In 2 of 10 case reports this information was
missing (LaRoche & Shivdat-Nanhoe, 2011; Parkerson
et al., 2011). One 8-year-old patient received LCM as
eighth drug, following treatment with LZP, PHE, PB, VPA,
LEV, FBM, TPM, and other therapies (propofol, corticos-
teroids, IV immunoglobulin, and plasmapheresis). One
patient received LCM as the second drug (Kellinghaus
et al., 2009).
Case series
In group I, there were 63% (35/56) NCSE, 23% (13/56)
focal SE, and 14% (9/56) CSE. Half (28/56) were responders:
among these, 43% (12/28) had NCSE, 29% (8/28) focal SE,
and 11% (3/28) CSE. Comparing the different types, there
was more focal SE in the responder group (eight patients, vs.
one nonresponder) but no notable differences for NCSE (12
vs. 16 responders/nonresponders) or CSE (three responders,
three nonresponders). In one study of 13 patients, the type of
SE was not specified (Cherry et al., 2012).
In group I the outcome in terms of seizure control varied
enormously, between 0% and 100%: 0% (1/7 studies: nine
patients with NCSE; Goodwin et al., 2011), 20% (1/7 stud-
ies: 2/10 patients; one NCSE, one focal SE; Rantsch et al.,
2011), 38% (1/7 studies: 5/13 patients; types of SE of non-
responders were not reported; Cherry et al., 2012), 70%
(1/7 studies: 7/10 patients with NCSE; Mnatsakanyan et al.,
2012), and up to 100% (3/7 studies: four patients with
NCSE; Koubeissi et al., 2011; and seven patients with par-
tial SE; Albers et al., 2011). In the studies with 100%
responders, the loading dose ranged from 50 mg (Koubeissi
et al., 2011; median 100 mg [range 50–100 mg]; four
NCSE) to 400 mg (Albers et al., 2011: four had focal SE).
In the remaining four studies, the initial dose of LCM varied
from 50 mg (Rantsch et al., 2011: 50–100 mg; eight NCSE,
two focal SE) to a maximum of 400 mg (Cherry et al.,
2012; mean initial dose 180.8 [range 100–400]; Mnatsaka-
nyan et al., 2012: 200 mg LCM/12 h). In the study with
100% nonresponders to LCM (six NCSE, three CSE), the
median initial dose was 200 mg (range 100–300 mg)
(Goodwin et al., 2011). Overall, the initial dose of LCM
responders (Albers et al., 2011; Koubeissi et al., 2011; Jain
& Harvey, 2012; Mnatsakanyan et al., 2012) versus nonre-
sponders (Goodwin et al., 2011; Rantsch et al., 2011;
Cherry et al., 2012) did not differ.
In group II, there were 39% (27/70) NCSE, 37% (26/70)
focal SE, and 24% (17/70) CSE. The responder rate varied
from 44% (17/39) (Kellinghaus et al., 2011) to 81% (25/31)
(H€ofler et al., 2011) of patients with SE. In the collaborative
study of Germany, Austria, and Switzerland (Kellinghaus
et al., 2011), the median initial dose of LCM was 400 mg
(range 200–400 mg). In our groups study, the median initial
dose of LCM was 200 mg (range 200–400 mg). In both
studies, median use of LCM was as third drug (H€ofler et al.,
2011; Kellinghaus et al., 2011).
Epilepsia, 54(3):393–404, 2013
doi: 10.1111/epi.12058
The loading dose of LCM was higher in group II (200–
400 mg) than in group I (50–400 mg).
Titration Time
Given the retrospective nature of the studies and varia-
tions in reporting strategies, it is difficult to evaluate titra-
tion times: this information was supplied only in case
reports, not in case series.
Single case reports
Chen et al. (2011) used a titration time of 8 days to reach
a daily dose of 400 mg in a case of partial SE. In the case of
the 8-year-old patient (Shiloh-Malawsky et al., 2011),
LCM was administered at a dose of 25 mg twice daily, with
resolution of SE after 5 days. In the case reported by Kel-
linghaus et al. (2009) IV LCM was administered as a 200-
mg bolus within 3–5 min, followed by oral LCM 100 mg
twice daily from day 2. In the study described by Torres-
Cano et al. (2011), LCM was given at a dose of 200 mg/
12 h. All patients reported by case reports were responders
to IV LCM.
Duration of SE until LCM
Therapy
Single case reports
Duration of SE until LCM application was detailed in 5
of 10 case reports (Kellinghaus et al., 2009; Chen et al.,
2011; Krause et al., 2011; Shiloh-Malawsky et al., 2011;
Torres-Cano et al., 2011). The longest duration of SE—
10 weeks (CSE evolving in a NCSE) until LCM was used—
was described by Shiloh-Malawsky et al. (2011). SE
appeared to resolve with LCM treatment. The shortest dura-
tion of SE before LCM was 1.5 h (Kellinghaus et al., 2009).
All reported patients were responders.
Case series
In group I, duration of SE until LCM therapy was
reported in four of seven case series (Goodwin et al., 2011;
Koubeissi et al., 2011; Cherry et al., 2012; Jain & Harvey,
2012). Goodwin et al. had a median time span of 48 h
(range 0–336 h); Koubeissi et al., 3–50 h. Cherry et al.
had a median duration of 39.5 h (range 6.5–74 h), whereas
Jain & Harvey reported 8–29 h duration of SE prior to
LCM.
In group II, duration of SE until LCM therapy was
reported only in one case series (Kellinghaus et al.,
2011). Patients had a median latency of 30 h (range 0.5–
1,440 h) in SE before they received LCM. However, both
studies in group II could demonstrate a clear order effect:
if LCM was administered early, it was successful in 60%
of cases, whereas the success rate was only 20% in more
refractory patients (H€ofler et al., 2011; Kellinghaus et al.,
2011).

Definition of Resistant SE
All contemporary protocols use a staged approach for
treatment of SE (Trinka, 2007; Kurthen et al., 2008; Shor-
von et al., 2008; Meierkord et al., 2010). Treatment in stage
1 (“early SE”) includes benzodiazepines. After the failure of
benzodiazepines, the next level will be stage 2 (“established
SE”), the most commonly used therapies being IV AEDs
such as PHE, PB, or VPA. If seizures continue despite this
treatment, the SE is classed as stage 3 (“refractory SE”), at
which point general anesthesia is recommended (Trinka,
2007; Shorvon et al., 2008).
Single case reports
All reported 10 patients with SE treated with LCM ini-
tially received benzodiazepines (Kellinghaus et al., 2009;
Tilz et al., 2010; Turpin-Fenoll et al., 2010; Chen et al.,
2011; Granda-Mendez et al., 2011; Krause et al., 2011;
LaRoche & Shivdat-Nanhoe, 2011; Shiloh-Malawsky et al.,
2011; Torres-Cano et al., 2011).
Case series
In 16% (13/126) of episodes of SE, benzodiazepines were
not given before initiation of LCM therapy (Albers et al.,
2011; H€ ofler et al., 2011; Kellinghaus et al., 2011; Rantsch
et al., 2011; Cherry et al., 2012); in 20% (16/126) of epi-
sodes of SE, LCM was given immediately after benzodiaze-
pines (Kellinghaus et al., 2009; H€ ofler et al., 2011).
Because dose information was missing regarding AEDs
received before LCM, a detailed analysis of prior treatment
was not possible.
Conclusion
In summary, 136 episodes of SE treated with LCM were
reported. The type of SE was an NCSE in 50% (69/136 epi-
sodes), focal in 31% (40/135), and convulsive in 19% (26/
135). Fifty-one percent (70/136) had preexisting epilepsy.
The overall success rate was 56% of SE (76/136). AEs were
reported in 25% (34/136) of patients: sedation in 25 cases, 1
patient with possible angioedema, 2 with allergic skin reac-
tion, 4 with hypotension, and 1 with pruritus. One patient
developed a third-degree AV block and paroxysmal asystole
(Krause et al., 2011). Overall, the rate of AEs was low.
None of the published studies had a prospective design,
and all were uncontrolled. Study design, heterogeneity of
population, and variations in the definition of SE may have
contributed to bias, in addition to the publication bias. The
varying—and sometimes missing—definition of response
to IV LCM also weakens the conclusions. Although LCM is
a promising drug in the treatment of acute seizures and SE,
several issues remain to be clarified: What is the right dose?
What is the maximum tolerated rate of infusion? How does
LCM penetrate across the blood–brain barrier in patients
with SE? Based on the current limited evidence LCM may
403
IV Lacosamide in Seizure Emergencies
have a potential as second-line alternative to standard
anticonvulsants in treatment of established SE, in case of
contraindications to phenytoin or valproic acid. The avail-
able evidence of efficacy is limited and randomized con-
trolled data are needed.
Acknowledgments
The authors thank Alison Terry for editorial work.
Disclosure
J. H€ofler has received speakers honoraria from UCB, and travel grants
from UCB, Eisai, and Gerot E. Trinka has acted as a paid consultant to
Eisai, Biogen Idec, Medtronics, Bial, and UCB. He has received research
funding from UCB, Biogen-Idec, Sanofi-Aventis, Red-Bull and speakers’
honoraria from Bial, Cyberonics, Desitin Pharma, Eisai, Gerot, B€ohringer-
Ingelheim, Sanofi, Medis, and UCB. We confirm that we have read the
Journals position on issues involved in ethical publication and affirm that
this report is consistent with those guidelines.
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