Epilepsia, 51(10):22072210, 2010
doi: 10.1111/j.1528-1167.2010.02646.x
BRIEF COMMUNICATION
Oral pregabalin as an add-on treatment for status epilepticus
Jan Novy and Andrea O. Rossetti
Service de Neurologie, CHUV and Universite de Lausanne, Lausanne, Switzerland
SUMMARY
Oral antiepileptic drugs (AEDs) represent possible add-
on options in refractory status epilepticus (SE). In this set-
ting, pregabalin (PGB) has not been reported before.
Over the last 42 months, we identified 11 SE episodes (10
patients) treated with PGB in our hospital. Its use was
prompted by the favorable pharmacokinetic profile,
devoid of drug-drug interactions. The patients mostly had
refractory, partial SE. Only two patients were managed in
Status epilepticus (SE) represents a serious condition,
with considerable morbidity and mortality. Its emergency
treatment usually consists of intravenous administration
of benzodiazepines followed by antiepileptic drugs
(AEDs) (mostly phenytoin, valproate, or phenobarbital)
(Shorvon, 2001). Although in SE refractory to this
approach anesthetics agents are often advocated, other
AEDs might be used instead, in order to prevent mechani-
cal intubation and related complications. Among AEDs of
the new generation, only topiramate (Towne et al., 2003),
levetiracetam (Rossetti & Bromfield, 2006; Knake et al.,
2008), and, more recently, lacosamide (Kellinghaus et al.,
2009) have been described in this context. Although the
latter two are available in intravenous formulations, topi-
ramate can be administered only through the nasogastric
tube.
Pregabalin (PGB) has been on the market since late
2006. Despite being available only as an oral formulation,
this compound represents a potentially interesting option
for critically ill patients, as it can be titrated quickly (Ram-
say et al., 2009), has good oral bioavailability, and is
devoid of hepatic interactions (Ben-Menachem, 2004). We
describe here our experience regarding PGB use in sub-
jects with SE.
Accepted April 12, 2010; Early View publication June 7, 2010.
Address correspondence to Dr. Andrea O. Rossetti, Service de
Neurologie, CHUV-BH07, CH-1011-Lausanne, Switzerland. E-mail:
andrea.rossetti@chuv.ch
Wiley Periodicals, Inc.
2010 International League Against Epilepsy
2207
the intensive care unit (ICU). We found a definite electro-
clinical response in 5 of 11, already evident 24 h after PGB
introduction, and a possible response (concomitantly with
other AEDs) in 3 of 11 of the episodes; 3/11 did not
respond. The treatment was well tolerated. Partial SE
appeared to better respond than generalized convulsive
SE. PGB appears to be an interesting option as add-on
treatment in refractory partial SE.
KEY WORDS: Complex-partial status epilepticus, Outcome,
Serum level.
Methods
In our prospective database of patients treated for SE in
our center (a tertiary referral hospital) between April 2006
and September 2009, we searched for episodes in which
PGB was prescribed. The database, which includes patients
older than 16 and received full approval from our ethics
commission, has been described previously (Novy et al.,
2010). Briefly, SE was defined as the clinical occurrence of
ongoing or repeated epileptic seizures without full recovery
in between for more than 30 min. If a patient with simple
partial seizures presented two or more seizures over at least
30 min without clinical recovery in between, this was con-
sidered SE. The type of SE was determined according to the
type of the worst seizure (categorized as simple partial,
complex partial, or generalized convulsive). All patients
underwent repeated electroencephalography (EEG) or EEG
monitoring; brain imaging [computed tomography (CT) or
magnetic resonance imaging (MRI)], laboratory workup,
and cerebrospinal fluid (CSF) analysis were performed as
needed.
Demographic and clinical data were retrieved from the
database and the computerized patients charts of our hospi-
tal, including information about cardiovascular or other pos-
sible side effects of medication (particularly, vigilance
worsening). SE refractoriness was defined as resistance to
benzodiazepines and the first AED in adequate doses.
SE termination was defined as resolution of clinical ictal
signs along with disappearance of continuous or repetitive
epileptiform discharges on the EEG, assessed at least
daily. SE response to PGB was categorized as successful
2208
J. Novy and A. O. Rossetti
(occurring within 24 h following PGB introduction, without
modification of concomitant AED), possible (SE termina-
tion associated with introduction/increase of PGB concomi-
tantly with other medications), or unsuccessful (no response
to PGB treatment). Outcome was measured at hospital
discharge, according to the GlasgowPittsburgh Cerebral
Performance Categories (CPC) (Booth et al., 2004), with
CPC 12 defined as good outcome.
Results
Among 230 SE episodes that occurred over 42 months,
we identified 15 in which PGB was prescribed. Four
patients were already treated with PGB before the index
SE, and the dosage was not modified; they were, therefore,
excluded. Clinical data of the remaining 11 episodes (10
patients, episodes six and eight occurred in the same sub-
ject, the second one following PGB withdrawal) are sum-
marized in Table 1. We observed a female predominance
(10 of 11), with a median age of 57 years (range 2080
years). Most patients had partial SE (9 of 11), and SE was
most often refractory (9 of 11). We diagnosed an acute
symptomatic etiology in four cases, and three patients had
de novo SE.
In all episodes, PGB was used as an add-on after failure
of other compounds to control SE. The treatment was
administered orally in patients with simple-partial SE and
through the nasogastric tube in patients who were deeply
somnolent or stuporous. In these cases, the capsule was
opened and the powder was admixed with water and
injected. The median latency to PGB introduction after SE
diagnosis was 5 days (range 0105 days). The median daily
target dose was 450 mg (range 150600), prescribed in two
fractioned administrations; this was achieved after a median
of 2 days (range 113 days). PGB residual serum level was
measured in episodes 5, 6, 7, and 11, with results within the
therapeutic range (median 31 lmol/L; range 1950 lmol/L;
therapeutic range in our lab 555 lmol/L).
Considering all 11 episodes, there was no clinical
response to PGB in 3, whereas 3others possibly responded.
Five episodes were very likely controlled by PGB, and the
response occurred within 24 h after PGB introduction.
Regarding SE subgroups, 5 of 9 of partial SE episodes ver-
sus 0 of 2 of generalized convulsive episodes were respon-
sive to PG; however, PGB was started after more than
1 month in both generalized convulsive cases. SE duration
before PGB introduction, as well as PGB titration speed or
target dosage, did not show any clear correlation with
treatment success, possibly owing to the limited sample
size.
All patients were discharged alive, with 9 of 11 achieving
a good outcome according to their CPC. PGB administra-
tion did not produce any cardiovascular side effects, and
there was no reported complication. Particularly, there was
no need for mechanical ventilation because of a sedating
Epilepsia, 51(10):22072210, 2010
doi: 10.1111/j.1528-1167.2010.02646.x
effect, and the medication was retained until hospital dis-
charge in all episodes.
Discussion
We report here our experience concerning patients with
mostly refractory SE treated with add-on PGB. This rela-
tively small series, which to the best of our knowledge rep-
resents the first description of the use of this compound in
SE, suggests that PGB is efficacious and well tolerated in
this setting.
PGB showed a good tolerability, and was efficacious at
usual dosages (150600 mg/day, with therapeutic serum
levels), with a responder rate (45%) similar to that of previ-
ous reports on oral levetiracetam (Rossetti & Bromfield,
2006). The treatment was efficacious even if adminis-
tered by the oral route, as already described for topira-
mate (Towne et al., 2003) and levetiracetam (Rossetti &
Bromfield, 2006): this corroborates our recent observation
that intravenous administration is not always imperative for
refractory SE (Novy et al., 2010). The five responders
improved their clinical condition within 24 h of PGB
administration; the fast action of this compound in SE
reflects recent data on patients with refractory epilepsy
(Ramsay et al., 2009). Three further patients responded
after 48 h, but since they also received increasing doses of
other AEDs, it is difficult to judge the specific role of PGB.
The clinical response appeared to be better in partial as
compared to generalized convulsive SE; this should, how-
ever, be put into the context of the considerable delay of
PGB administration in the two patients with generalized
convulsive SE, suffering from a severe refractory SE with
multiple intensive care unit (ICU) complications that possi-
bly affected intestinal resorption. A long delay before SE
treatment is known to represent an important predictor of
poor response (Shorvon, 2001; Rossetti & Bromfield,
2006), especially in the first 2448 h (Drislane et al., 2009).
It is interesting to note that the administration through the
nasogastric tube (that occurred in the three nonresponders)
does not seem to have significantly altered the drug absorp-
tion, since the PGB serum level was in the reference interval
in two patients. Titration speed or the target dosage of PGB
did not appear to determine the clinical response.
From a theoretical perspective, PGB could represent a
good pharmacodynamic complement to sodium channel
blockers, c-aminobutyric acid (GABA) agonists or other
wide-spectrum AEDs used in SE, owing to its calcium
channel modulation (Dooley et al., 2000). Moreover, this
compound has an extremely favorable pharmacokinetic
profile, with pure renal elimination and no interactions with
others drugs, suggesting that PGB is particularly useful in
subjects needing other treatments, such as AEDs, antibiot-
ics, immunosuppressives, or cytostatic chemotherapy. The
fact that our patients were already receiving polypharmacy
and we wanted to avoid pharmacokinetic interactions
 Table 1. Summary of patients data
PGB
PGB maximal Time between Serum
Previous Seizure Outcome Intubated for Other Time to PGB titration dosage PGB introduction levels
N Gender Age seizures Etiology type Consciousness (CPC) Refractory treatment treatments introduction time (mg/day) success? and response (lmol/L)
1 F 74 No Acute SP Somnolentb 2 Yes No CLZ, LEV 5 days 1 day 150 Yes 24 h
hemorrhage
2 F 64 Yes Glioma SP Alertb 2 Yes No CLZ, LEV 1 day 3 days 600 Yes 24 h
WHO IV
3 M 57 Yes Poor CPa Stuporous 1 Yes No CLZ, LEV 5 days 2 days 300c No
compliance
4 F 50 Yes Glioma SP Alertb 1 Yes No CLZ, LEV 0 day 1 day 150 Possible 48 h
WHO IV (with LEV
increase)
5 F 80 No Meningioma CP Confused 3 Yes No CLZ, LEV, PHT 2 days 5 days 450 Possible Progressive 50
improvement
during titration
6 F 63 Yes Old CP Confused 1 Yes No CLZ, LEV, VPA 6 days 2 days 450c Possible 72 h 30
hemorrhage (with VPA
increase)
7 F 34 Yes Cryptogenic CP Confused 1 Yes No CLZ, PHT 4 days 3 days 600 Yes 24 h 32
8 F 64 Yes Poor CP Confused 1 No No CLZ 0 day 1 day 600 Yes 24 h
compliance
9 F 57 Yes Glioma CP Stuporous 2 No No VPA 5 days 2 days 300 Yes 24 h
WHO III
10 F 25 Yes Anti-NMDA GC Stuporous 2 Yes Yes PB, PHT, MDZ 31 days 2 days 600c No 19
encephalitis
11 F 20 No Cryptogenic GC Stuporous 3 Yes Yes MDZ, PHT, 105 days 12 days 600c No
LEV, PRO, TPM
Seizure types are categorized as generalized convulsive (GC), complex partial (CP), or simple partial (SP). Outcome was assessed according to GlasgowPittsburgh Cerebral Performance Categories (Booth et al.,
2004).
CLZ, clonazepam; LEV, levetiracetam; PHT, phenytoin; VPA, valproate; PB, phenobarbital; MDZ, midazolam; TPM, topiramate; PRO, propofol; F, female; M, male; WHO, World Health Organization (grade); NMDA.
N-methyl-D-aspartate.
a
Patient 3 presented initially with generalized convulsive SE that evolved into partial complex SE; he was treated in this second phase with PGB.
b
Among patients with simple partial SE, two patients had motor and aphasic symptoms; the last patient had motor symptoms and was already somnolent before the SE because of brain hemorrhage.
c
Given through the nasogastric tube.
Pregabalin in Status Epilepticus

doi: 10.1111/j.1528-1167.2010.02646.x
Epilepsia, 51(10):22072210, 2010
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2210
J. Novy and A. O. Rossetti
probably led to a selection of our patients, who had brain
tumor or encephalitis in about half of the cases.
This study is limited by its small sample size. Moreover,
although our patients mainly had refractory SE, almost half
of them had self-limited conditions as self-limited SE etiol-
ogies, and most of them also were known for previous sei-
zures, a feature considered to herald a better prognosis than
de novo episodes (Holtkamp et al., 2005). The uncontrolled
aspect of this study also limits the significance of the results.
However, a regression to the mean, that is, a spontaneous
SE resolution, is unlikely to have occurred in our patients,
since refractory SE is rarely self-limited.
In our opinion, since refractory SE may at times be man-
aged outside of the ICU (Novy et al., 2010), the adjunction
of PGB could represent an interesting alternative in partial
refractory SE before considering coma induction, which has
a potential burden of complications.
Acknowledgments
Dr. Rossetti received research support from UCB, Pfizer, Astra-Zeneca,
and Janssen-Cilag.
Disclosure
Dr Novy has nothing to disclose. We confirm that we have read the Jour-
nals position on issues involved in ethical publication and affirm that this
report is consistent with those guidelines.
Epilepsia, 51(10):22072210, 2010
doi: 10.1111/j.1528-1167.2010.02646.x
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