Curr Geri Rep (2014) 3:7382

DOI 10.1007/s13670-014-0078-5

NEUROLOGY OF AGING (KS MARDER, SECTION EDITOR)

Management of Seizures in the Elderly

Cynthia M. Correll & Carl W. Bazil

Published online: 8 April 2014

# Springer Science+Business Media New York 2014

Abstract Contrary to what most physicians believe, seizures

begin most commonly in the older age group (early childhood
is the next most common time). In older patients, detailed
history may be even more important to differentiate seizures
from other transient neurological complaints often seen at that
age. Electroencephalography and magnetic resonance imaging of the brain can also be helpful in the diagnosis.
As there are now numerous antiepileptic drugs to
choose from, potential adverse effects and drug interactions, as well as efficacy, are particularly important in older
patients. This review will outline the diagnosis and causes of
seizures in the elderly, as well as the clinical trials and side
effect profiles that will help guide management decisions in
this age group.
Keywords Epilepsy . Seizure . Elderly . Aged . Old .
Management . Treatment . Antiepileptic drug . Differential
diagnosis . Side effect

Introduction
Epilepsy, or recurrent unprovoked seizures, is a chronic disease initially thought to be more prevalent in the young.
Epidemiological research over the past 40 years has revealed
a bimodal distribution in new cases of epilepsy, with old age
being the most common time to develop seizures [14, 5]. In
fact, the elderly account for 2530 % of all new cases of
C. M. Correll (*) : C. W. Bazil
Columbia Comprehensive Epilepsy Center, Columbia University
College of Physicians and Surgeons, 710 W. 168th Street, New York,
NY 10032, USA
e-mail: cmc2235@columbia.edu
C. W. Bazil
e-mail: cwb11@columbia.edu

seizures [4, 6], and this statistic is likely to increase with our
aging population. Incidence cases of epilepsy in the elderly,
generally agreed upon as 65 years and above, have ranged
from 70 to 240 cases per 100,000 person years in various
studies [5, 7, 8]. These numbers are much higher than the
population as a whole (~ 50 cases of epilepsy per 100,000
person years). An early study by Tallis et al. [1] found increasing seizure incidence rates by decade above 60 years: 69 cases
per 100,000 person years in the general population, 76 cases
per 100,000 person years in the population above age 60, 147
cases per 100,000 person years in the population above age
70, and 159 cases per 100,000 person years in the population
above age 80. The elderly are not only at increased risk for
epilepsy, they are also at increased risk for status epilepticus,
with 830 % of the elderly with new onset seizures presenting
in status epilepticus [9, 10, 11, 12]. Moreover, rates of both
morbidity and mortality are higher in the elderly presenting
with seizures or status epilepticus compared to the general
epilepsy population [7, 13].
In addition to increased mortality, patients quality of life is
significantly affected by epilepsy, and this effect appears to be
magnified in the elderly. A study in the UK documented that a
groups of men with epilepsy over age 65 and women with
epilepsy over age 60 reported a worse quality of life compared
to younger patients with epilepsy. Quality of life was measured using a questionnaire containing an impact of epilepsy
scale, adverse drug events profile, hospital anxiety and depression scale, and stigma scale. [14]. Studies comparing
elderly with epilepsy to age-matched controls have found
significant differences in measures of psychosocial wellbeing, emotional adjustment, perception of stigma, depressive
and anxiety symptoms, memory and concentration tests, and
sleep, though these studies did not control for the etiology of
seizures, such as stroke, which can also impact quality of life
measures [15, 16]. These findings further highlight the need
for prompt and appropriate care of seizures in the elderly.

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Diagnosis
Prior to starting treatment, it is important to determine if a
seizure disorder is in fact the correct diagnosis. Because the
gold standard of diagnosis, an abnormal electroencephalogram (EEG) during an epileptic seizure, is difficult to obtain,
a detailed and thorough history is the key to diagnosing
seizures. Patients often have incomplete or complete lack of
recollection of a seizure. Even when fully conscious of the
event, patients often have a difficult time describing symptoms without direct and informed questioning; this is heightened in the elderly who frequently live alone or in facilities,
and are at high risk for memory problems and dementia. When
in doubt, referral to a neurologist with training in epilepsy is
advised if there is a high suspicion for seizure [17].
Confusional or transient amnestic states, such as syncope/
arrhythmia, vertigo, metabolic disturbances (hypoglycemia,
nonketotic hyperglycemia, and medication toxicity), transient
global amnesia, complex migraines, and transient ischemic
attacks, are commonly mistaken for seizures in the elderly
[1820]. There are a number of classic complaints or symptoms that can lead to one of these differential diagnoses.
Syncopevasovagal, orthostatic, or due to an arrhythmia
is often proceeded by a prodrome of lightheadedness, darkening of vision, diaphoresis, and even nausea. While brief convulsive movements or myoclonic jerks following syncope are
fairly common, patients usually return to baseline mental
status quickly without the post-ictal confusion commonly
witnessed after seizures. Transient global amnesia is a profound confusional state with no alteration in consciousness.
The clinical presentation of this syndrome is characterized by
repetitive questions, such as where am I, due to a combination of retrograde and anterograde amnesia. Episodes typically
last for hours, which can help differentiate it from a complex
partial seizure typically lasting only a few minutes [19]. Focal
motor weakness can be seen post-ictally following a seizure,
in a phenomenon termed Todds paresis, but it should not be
the only symptom reported. Isolated motor weakness without
a preceding episode of impaired consciousness or clonic motor movements is much more suggestive of a transient ischemic attack than a complex partial seizure. A complex migraine
should be suspected if focal neurological symptoms are associated with a transient headache. Timing of the headache can
be helpful, because while headaches are common following a
convulsion, they are much more rare preceding or during a
seizure.
Sleep disorders are another category of neurological disorders commonly mistaken for seizures. Parasomnias are paroxysmal motor behaviors that occur without the patients
awareness during various stages of sleep [21]. Non-REM
sleep disorders are characterized as confusional arousals, somnambulism (sleep walking), or sleep terrors. Sleep terrors are
the most dramatic with associated agitated behavior and

Curr Geri Rep (2014) 3:7382

prominent autonomic features. Non-REM sleep disorders

commonly start earlier in life and rarely continue into old
age. On the other hand, REM sleep behavior disorder (RBD)
is much more common in the elderly. It is caused by a loss of
atonia during REM sleep, resulting in the patient acting out
their dreams, frequently displaying violent behavior. RBD can
occur acutely, often in the setting of medications (i.e. tricyclic
antidepressant use, SSRI use, or alcohol/benzodiazepine withdrawal), or chronically associated with other neurological
disorders such as Parkinsons disease, multiple systems atrophy, narcolepsy, and dementia [22]. Of note, RBD can actually present decades prior to onset of degenerative disorders.
Sleep disorders are commonly mistaken for seizures, particularly frontal onset, as these have nocturnal predominance and
complex motor semiology. Compared to parasomnias, frontal
lobe seizures are more brief and stereotyped, although with
incomplete history; especially when a witness is not available,
definitive diagnosis can be challenging.
Psychogenic non-epilepsy seizures (PNES), which on average account for 30 % of referrals to epilepsy monitoring
units, must always be on the differential when considering an
epilepsy diagnosis. While population studies have shown
PNES is most common in the 1524-year-old age group,
multiple studies have identified PNES in the elderly, especially in the population being referred for inpatient video-EEG
monitoring [2325]. A single study looking at the etiology of
PNES in the elderly found a higher rate of traumatic experiences associated with physical health issues compared to
younger patients, who were more likely to report sexual abuse
or trauma [24].
It is also important to diagnose provoked seizures, which
resolve with correction of the insulting agent or abnormality
and do not lead to long-term epilepsy. Metabolic disturbances
such as hyponatremia, hypoglycemia, hypocalcemia, and uremia should be assessed for and treated. Numerous medications
have been shown to induce seizures, or lower the seizure
threshold. These include antidepressants (e.g., bupropion),
antipsychotics (e.g., clozapine and chlorpromazine); opioid
narcotics (e.g., meperidine), CNS stimulants (e.g., amphetamines), antihistamines, chemotherapeutic agents, immunosuppressants (e.g., tacrolimus and cyclosporine), and antibiotics (e.g., fluoroquinolones). Transient treatment with an
antiepileptic medication may be necessary in the setting of
drug-induced status epilepticus or a seizure cluster, but can
usually be discontinued after withdrawal of the offending
agent.

Causes
The etiology of epilepsy in the elderly differs significantly
from the causes in younger patients, with the most common
being stroke and dementia. Tumors, infection, and trauma also

Curr Geri Rep (2014) 3:7382

account for a percentage of seizures; however, the majority of

epilepsy cases in the elderly are cryptogenic in etiology. One
of the early studies on the etiology of new-onset seizures in
151 patients over age 60 found that 32 % were caused by a
stroke or bleed [26]. A number of studies since then have
found similar statistics [2, 6, 9], or even higher rates of
epilepsy caused by strokes in the elderly compared to the
general epilepsy population (49 % and 46 % in the elderly
vs. 16 % and 30 % in the general population, respectively) [27,
28]. Of note, the risk of both early and late onset seizures are
greatly increased after a stroke or bleed [12, 29, 30, 31].
A recent study of 421 patients with various types of cerebrovascular disease found an 11.6 % seizure prevalence with
mean follow-up of 30 months [12]. This equated to a 4.6 %
annual risk of seizures (4.1 % annual risk for ischemic strokes
only). Of the patients with seizures, 42.9 % had a single
seizure and 57.1 % had multiple seizures consistent with
epilepsy. Of note, patients were more likely to have recurrent
seizures, or epilepsy, if their first seizure occurred late rather
than in the acute phase of stroke. Other studies have suggested
that larger strokes, cortical involvement, preserved cortical
islands within the area of the stroke, and hemorrhagic stroke
all increase the risk for seizures [30, 3234]. Rossi et al. [29]
recently looked at 325 patients with intracerebral hemorrhages
and found an incidence rate of 9.5 % for late seizures over
only a mean follow-up of two years, showing that the risk of
epilepsy is even higher for bleeds than ischemic strokes.
Again, there was an increased risk of seizures with cortical
involvement of the bleed. While altogether these studies show
that stroke is a very common cause of epilepsy in the elderly, it
should be noted that there is no indication to prophylactically
start an antiepileptic drug (AED) in patients who have experienced a stroke if they have not had a seizure, as most will
remain seizure free [35, 36].
Epidemiological studies have indicated that dementia accounts for 712 % of epilepsy cases in the elderly [2, 9, 18].
One study that looked at a subset of elderly patients over age
75 reported dementia as causing seizures in as much as 20 %
of this population [3]. A number of prospective and retrospective studies have shown prevalence rates of seizures, or epilepsy, from 1.5 to 9 % in patients with Alzheimers disease
[3740]. A recent large population based study with casecontrols in the UK found an epilepsy incidence of 5.6/1000
person years in patients with Alzheimers disease and 7.5/
1000 per years in patients with vascular dementia, compared
to 0.8/1000 person years in dementia-free controls [41].
Hesdorffer et al. [42] studied a group of patients over age 55
with new onset epilepsy and found that patients with dementia
other than Alzheimers disease had a similar increased risk of
epilepsy as patients with Alzheimers disease, about six-fold,
compared to case-matched controls. Tumor, traumatic brain
injury, and infection are less frequent causes of epilepsy in old
age, but still greatly increase the risk of a patient developing

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epilepsy. Malignant tumors such as astrocytomas,

oligodendrogliomas, glioblastoma multiforme, and brain metastases are more commonly the cause of epilepsy in the
elderly compared to benign tumors such as gangliogliomas
and dysembryoplastic neuroepilethelial tumors more commonly found in children. Meningiomas, which are typically
benign as well, can also cause seizures in the elderly. Similar
to the stroke literature, there is consensus that patients with
neoplasms should not be placed on prophylactic antiepileptic
medications if they have not had a seizure [43].

Management
When it has been decided that the presenting event was a
seizure, the next decision that must be made is whether the risk
of seizure recurrence is high enough to warrant chronic antiepileptic drug (AED) use. Population wide studies have generally shown seizure recurrence risk to be anywhere from 30
to 50 % after a first unprovoked seizure [44, 45]. Therefore,
patients are not generally treated after a first seizure unless an
abnormality that increases recurrence risk is found on workup
with a routine EEG or magnetic resonance imaging (MRI) of
the brain. Seizure recurrence rates greatly increase after a
second unprovoked seizure, and therefore, antiepileptic therapy should start after a second seizure even if the EEG and
MRI of the brain are normal. In the elderly population with a
first seizure, seizure recurrence rates of 3780 % have been
reported [8, 20, 26], with some authors using these numbers to
suggest starting treatment in all elderly patients with a first
time unprovoked seizure. This is not an agreed upon conclusion among all neurologists, and most will perform a complete
workup with EEG and MRI of the brain prior to making a
decision about treatment. Some also suggest that risk of serious injury with seizure recurrence is greater in the elderly
(broken bones, subdural hematoma), such that AEDs might
be recommended at a lower recurrence risk than in the young.
If there is a history of illness that increases the risk for epilepsy
such as stroke, dementia, tumor, or central nervous system
(CNS) infection, antiepileptic treatment should begin after the
first seizure. Similarly, treatment should be initiated if MRI
reveals a structural lesion such as stroke or tumor that increases the risk for epilepsy, or if there is epileptiform activity
on EEG. It is important to note that routine EEG may be less
helpful in diagnosis of epilepsy in the elderly compared to
younger populations. An early study reported that routine
EEGs in the general epilepsy population show interictal epileptiform activity ~50 % of the time on the first EEG and up to
8090 % of the time by the third and fourth repeated EEGs
[46]. Reviews of outpatient EEG referrals in the elderly have
mostly shown low rates of epileptiform abnormalities
[4749], but the rates increase dramatically when looking only
at patients with a definite diagnosis of epilepsy. Waton et al.

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[50] found that routine EEGs at a single institution were

diagnostic in 11 % of the elderly patients referred and that
there was no significant difference in sensitivity or specificity
of routine EEGs in the elderly compared to younger age
groups. Drury et al. [51] found interictal epileptiform discharges in 35 % of patients over the age of 60 with epilepsy,
indicating routine EEG is still a useful tool in this age group.
Furthermore, prolonged ambulatory or inpatient continuous
EEG recording can improve the yield of abnormal findings in
the same way repeated routine EEGs have been shown to
increase the sensitivity of this test. For repeated potential
epileptic events, numerous studies have supported the role of
inpatient epilepsy monitoring unit admissions for the elderly
population [5255].
Antiepileptic Drug Trials
Once the decision to treat with an AED is made, selecting
which medication to use in the elderly epilepsy population can
be difficult. One reason is that there are few head-to-head trials
comparing AEDs in the general epilepsy population, let alone
the geriatric epilepsy population. Two original randomized
control studies compared older antiepileptic medications for
partial onset epilepsy in the general population [56, 57]. One
compared carbamazepine (CBZ) to phenobarbital (PHB),
phenytoin (PHT), and primidone [56] and the other compared
CBZ to valproate (VPA) [57]. The studies found significantly
lower adverse events with carbamazepine compared to the
other drugs, as well as better seizure control when comparing
CBZ to VPA. A large VA cooperative study found increased
cognitive effects with PHT and PHB [58]. These studies as
well as other data led to the consensus expert opinion statement in 2005 that PHT and PHB become second and third-line
antiepileptic medications, due to their increased adverse effects [59]. At that time, first-line medications for partial epilepsy were lamotrigine (LTG), gabapentin (GBP), CBZ,
oxcarbazepine (OXC), and levetiracetam (LEV). VPA and
LTG were cited as first-line therapy for primary generalized
epilepsy. After this statement, the SANAD trial compared
CBZ, GBP, LTG, OXC, and topiramate (TPM) for the treatment of partial epilepsy, showing that LTG faired significantly
better than CBZ, GBP, and TPM when comparing time to
treatment failure [60]. Other general epilepsy population studies have added to the data that LTG is more tolerable in the
general population compared to older generation AEDs such
as CBZ and PHT [61, 62].
In the elderly with partial onset epilepsy, there have been
three large randomized control trials. Rowan et al. [63] compared GBP, LTG, and CBZ in new onset geriatric epilepsy,
defined as patients 60 years of age or older with at least one
seizure in the past three months, and found higher retention
rates and decreased adverse effects with LTG and GBP compared to CBZ. It is important to note that these results speak to

Curr Geri Rep (2014) 3:7382

the increased tolerability, not efficacy, of LTG and GBP compared to CBZ. Brodie et al. [64] compared LTG to CBZ in the
elderly, age range 6594 years old, with newly diagnosed
epilepsy, defined as two or more seizures in the last year with
one in the past 6 months, and found higher seizure freedom
rates and lower adverse events with LTG use. On the contrary,
Saetre et al. [65] compared LTG to sustained-release CBZ, a
twice daily formulation compared to the three times daily
formulation used in the prior studies, and found no significant
difference in retention rates, seizure freedom rates, or adverse
events in an elderly group of patients age 6591 years old with
new onset epilepsy, defined as two or more seizures with one
in the past 6 months. These three studies did not adjust for or
analyze outcomes based on seizure etiology. Two of the three
studies did exclude patients with life expectancy less than
12 months or progressive neurological disease. Smaller single agent studies have shown acceptable efficacy and tolerability rates for many of the other newer antiepileptic
agents including OXC [66, 67], TPM [68, 69], and LEV
[7072]. An interesting multicenter randomized trial, comparing CBZ and LEV in late post-stroke seizures, found
increased adverse events and worse cognitive scores on
repeat neuropsychological testing in the group placed on
CBZ [73].
Antiepileptic Side Effects and Characteristics
Given the lack of sufficient head to head trials of antiepileptic
medications, the decision of which medication to start in the
elderly is largely dependent on side effect profiles (Table 1).
CBZ, while initially the gold standard for partial seizures in
the general population, has a number of side effects that likely
contributed to worse treatment withdrawal and adverse event
statistics in trials in the elderly. These include ataxia, rash,
hyponatremia, sexual dysfunction, and conduction block.
CBZ is an inducer of CYP450 hepatic metabolism and can
cause decreased serum levels of other AEDs, as well as other
commonly used medications in the elderly (i.e. warfarin,
simvastatin, and nimodipine). Because carbamazepine is also
metabolized through the CYP450 system, it is an autoinducer,
and other common enzyme-inducing drugs (i.e., cimetidine,
fluoxetine, erythromycin, isoniazid, diltiazem, verapamil, and
even grapefruit juice), can decrease the serum level of this
AED. Enzyme induction drug interactions are especially important in the elderly who are often on polypharmacy
regimens.
The older drugs PHT and PHB are also enzymeinducing agents with the same drug interaction problems.
Important side effects with PHT include ataxia, rash, gingival hyperplasia, sedation, conduction block, and irreversible cerebellar degeneration. Because PHT displays nonlinear kinetics, titration can be difficult, particularly in the
elderly. In addition to the enzyme inducing properties of

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Table 1 Antiepileptic drug (AED) advantages, disadvantages, side effects, and medication interactions
Drug

Advantages

Disadvantages

Side effects

Medication interactions

Phenytoin

Daily dosing, IV Formulation,

Inexpensive

Nonlinear kinetics, Protein bound,

Enzyme inducer

Ataxia
Somnolence
Rash
Osteoporosis

AEDs, warfarin,
Simvastatin,
cimetidine, Diltiazem,
propranolol, Isoniazid,
metronidazole

Phenobarbital

Inexpensive

Protein bound, Enzyme inducer

Sedation
Osteoporosis

Carbamazepine Effective for partial epilepsy

Autoinduction, Enzyme inducer,

Protein bound

Rash
Hyponatremia
Arrhythmias
Impotence
Osteoporosis

Valproate

Enzyme inhibitor, Protein bound

Somnolence
Tremor
Weight gain
Osteoporosis
Pancreatitis
Low platelets
Hyponatremia
Rash
Rash
Headache
Tremor
Insomia
Impaired cognition
Weight loss
Renal stones
Somnolence
Agitation/irritability
Somnolence
Weight loss
Agitation
Ataxia
Rash
Renal stones
Somnolence
Weight gain
Pedal edema
Somnolence
Weight gain
Sedation
Confusion
Somnolence
Ataxia
Conduction problems

AEDs, Warfarin,
Nimodipine
verapamil, Metronidazole
AEDs, cimetidine,
Fluoxetine,
Erythromycin,
verapamil,
Simvastatin, diltiazem,
Soniazid,
Metronidazole,
Doxycycline
AEDs

Effective for generalized epilepsy,

IV
formulation

Oxcarbazepine
Lamotrigine

Mood stabilizer, Tolerability

Topiramate

Levetiracetam

Moderate protein bound, Some

enzyme induction
Moderate protein bound, Slow
titration

Enzyme inducer at high doses

Zonisamide

Tolerability, Fast titration, IV

formulation
Daily dosing, Long half-life

Gabapentin

Tolerability

TID dosing, Renal excretion, Dose

limited absorption

Pregabalin

Tolerability

Renal excretion

Clobazam

Treats anxiety, Long half-life

Hepatic metabolism, Protein bound

Lacosamide

Renal excretion
Protein bound

Renal excretion

the drug, PHB very frequently causes cognitive side effects

and sedation, which significantly limits its use in the elderly population.
While VPA has been the gold standard for primary
generalized epilepsy, it is not as effective for partial onset
epilepsy, the most frequent type of new onset epilepsy in
the elderly [2, 3, 74]. Furthermore, VPA is an inhibitor of

AEDs, Estrogen ataxia

Levonorgestrel, depakote
estrogen, Zonisamide

AEDs

CYP450 hepatic metabolism causing increased levels of

AEDs and other medications. Significant side effects with
VPA include somnolence, encephalopathy, tremor, weight
gain, parkinsonism, pancreatitis, and thrombocytopenia.
VPA can be considered in patients with concomitant epilepsy and migraines since it is effective in both these
conditions.

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The newer antiepileptic agents have more favorable side

effects profiles and are much less likely to interact with other
medications. OXC has some selective enzyme induction and,
therefore, does interact with some medications. Significant
side effects include hyponatremia, ataxia, somnolence, rash,
and tremor. LTG, which is effective for both primary generalized and focal epilepsy, is generally well tolerated, but potential side effects include rash, headache, tremor and nausea.
TPM can cause weight loss, paresthesias, and renal stones. Its
use in the elderly is mostly limited by frequent memory
impairment, poor concentration and word-finding difficulty
[75]. Like VPA, it may be a better choice for patients with
migraine and epilepsy. GBP and pregabalin are both renally
excreted so dosing must often be adjusted in the elderly as
creatinine clearance rates decrease. They can both cause
weight gain and lethargy, but have no significant drug interactions. GBP use can be significantly limited by the three
times daily dosing regimen and dose limited absorption.
Gabapentin and pregabalin should be considered in patients
with epilepsy and coexistent neuropathic pain.
Zonisamide (ZNS) is associated with the side effects
of somnolence, ataxia, agitation/behavioral problems,
weight loss, rash, and kidney stones. It requires only
daily dosing, which can be of benefit in patients with
adherence issues. Of note, ZNS has been studied in the
treatment of Parkinsons Disease, and may be a good
choice in patients with Parkinsons Disease and epilepsy
[76]. Clobazam is a fast acting antiepileptic medication
with a long half-life and may also be beneficial in
patients with adherence issues. It is metabolized through
the liver so drug levels may be altered with enzyme inhibition or induction. The most significant side effect is somnolence. Like other benzodiazepine medications, cognitive or
behavioral abnormalities in the elderly are a concern however
anxiolytic effects can be beneficial. Lacosamide has been
associated with dizziness, ataxia, and cardiac conduction
problems. It is renally excreted and is not associated with
drug-drug interactions. Lastly, LEV is also generally well
tolerated with few side effects, but can cause somnolence
and agitation/behavioral problems. LEV does not have any
significant drug interactions. It is renally excreted so dosing
must be adjusted accordingly.
One of the medication side effects most concerning in the
elderly is bone loss and risk of osteoporosis. Initially, it was
thought that osteoporosis, or decreased bone mineral density
(BMD), was only caused by enzyme-inducing drugs such as
PHT, PHB, and CBZ. Subsequent data suggests certain
non-enzyme inducing drugs, such as VPA, also lower
BMD. Even newer drugs such as OXC, LEV, and ZNS
are now being associated with decreased bone mineral
density or bone strength [77, 78]. A number of studies
have shown an increased risk of fractures, not just osteoporosis, with prolonged use of antiepileptic drugs, and this

Curr Geri Rep (2014) 3:7382

increased risk is still significant when seizure-related fractures

are excluded [79, 80, 81].
Lazzari et al. [82] recently addressed the issue of osteoporosis prevention in elderly patients on AEDs with a randomized control trial of 80 patients assigned to 2 years of treatment
with a bisphosphonate (risedronate) plus calcium and vitamin
D versus placebo plus calcium and vitamin D. The bisphosphonate group showed a significant improvement in bone
mineral density at the lumbar spine compared to the placebo
group. There was also an increased number of fractures in the
placebo group, five vertebral and one nonvertebral, compared
to none in the bisphosphonate group. Although prophylactic
use of bisphosphonates is not standard of care for elderly
patients using AEDs, calcium and vitamin D supplementation
is advised. Furthermore, elderly patients on chronic AEDs
should have regular Vitamin D levels and DEXA scans.
Signs of osteoporosis should lead to prompt referral to an
endocrinologist, or experienced primary care doctor, to determine if they are a candidate for bisphosphonate therapy.

Treatment Algorithm

Figure legend: CBZ: carbamazepine; CLB: clobazam; GBP: gabapentin;LCM: lacosamide; LTG:
lamotrigine; LEV: levetiracetam; PGB: pregabalin; TPM: topiramate; VPA: valproate; ZNS: zonisamide

Fig. 1 Treatment algorithm. CBZ carbamazepine; CLB clobazam; GBP

gabapentin; LCM lacosamide; LTG lamotrigine; LEV levetiracetam; PGB
pregabalin; TPM topiramate; VPA valproate; ZNS zonisamide

Curr Geri Rep (2014) 3:7382

Nonadherence Issues
In determining a medication regimen, ability of the patient to
comply with the medication must also be taken into account.
Nonadherence to chronic medications is a common problem
in all age groups, but appears to be accentuated in the elderly.
A retrospective study of Medicaid claims for antiepileptic
medications found that noncompliance was more common
in patients aged 65 years or older [83]. Nonadherence rates
of 40 % and higher for AED use have been reported in the
elderly [84, 85]. Furthermore, nonadherence in this patient
population is associated with higher risk of mortality, increased hospitalization and ED visit, increased fractures and
other injuries, and higher healthcare costs [83, 84]. The elderly
are at increased risk for nonadherence for a multitude of
reasons including cognitive or memory impairments, the complexity of polypharmacy, and poor tolerance or side effects
[84]. Elderly patients are frequently on numerous medications
with complex dosing, which can be difficult to manage. In
fact, it has been shows that AED adherence decreases from
89 % for once daily dosing to 39 % for four times daily dosing
[86]. Additionally, the older patient often requires lower doses
of medications and can still have increased side effects at these
lower doses. Reasons for increased side effects and need for
lower doses in the elderly include decreased hepatic metabolism, impaired gastrointestinal absorption, decreased renal
clearance, decreased protein binding, altered drug distribution
due to changes in fat tissue, and decreased homeostasis at the
site of drug effect [17, 18, 8789]. The newer agents, such as
LTG and LEV, may be better tolerated and could lead to better
compliance [85]. Other suggestions to improve compliance
include supplementary education on the risks of seizures and
need for compliance, written medication instructions, simplifying polypharmacy regimens, and using extended release
formations to decrease peak dose side effects. Reminders such
as a pill box or smartphone alerts may also improve
adherence.
As in all age groups, the use of generic equivalents in
epilepsy should be met with additional caution due to the
greater potential for variability particularly with switching
between different generic manufacturers. For this reason, the
American Academy of Neurology recommends that changes
should not be made without the knowledge of the patient and
prescriber [90]. Blood levels may be necessary to ensure that
levels remain in the desired range when changes are made.
Medication Recommendations
Figure 1 shows an algorithm for choosing AEDs in the elderly.
It is important to remember that these choices are not based on
efficacy, as this is generally considered comparable, but by
drug interactions, adverse effect profiles, and other properties.
Lamotrigine, levetiracetam, and gabapentin are often

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preferable due to tolerability and lack of drug interactions;

carbamazepine and lacosamide are reasonable; however, carbamazepine has drug interactions and lacosamide is newer,
and use in monotherapy less accepted. Long half-life and once
daily drugs may be preferable in some patients for increased
compliance (lamotrigine and zonisamide); however, clobazam
or long-acting preparations of other drugs could also be considered. In cases with concurrent neuropathic pain, migraine,
or obesity specific drugs that also treat these could be considered. Phenytoin and phenobarbital should generally be
avoided in the elderly, due to drug interactions and adverse
effect profile; oxcarbazepine is less desirable due to risk of
hyponatremia.
Treatment Response and Surgical Options
Response to treatment has been reported as favorable in the
elderly, with perhaps even better antiepileptic drug response
rates than in the younger population. Kwan and Brodie [91]
reported seizure freedom rates in the general epilepsy population of 44 % after the first AED trial, 67 % after the second
AED trial, and 70 % after the third trial. Stephen et al. [92]
found seizure freedom rates in epilepsy patients age 65 or
older were 62 % after the first AED trial and 79 % after a
second AED was trialed. Besocke et al. [93] found even
higher seizure freedom rates in an older age group, with
77 % seizure free at 12 months on AED therapy. Even if the
elderly tend to respond better to AEDs, there will still be
significant number who do not respond to medications. In
the healthy elderly with medically refractory epilepsy, defined
as failure of two or more adequate trials of antiepileptic
medications, epilepsy surgery should be considered. Three
studies looking at surgical resection for temporal lobe epilepsy; with subject numbers of 7, 30, and 52 patients in the older
age groups; showed seizure freedom rates ranging from 50 to
70 %, which were comparable to their younger cohorts
[9496].

Conclusion
Seizures are found in a bimodal distribution, with one peak in
the very young, and with the most likely time to develop new
onset seizures being old age. As the number of elderly in our
population continues to grow, the healthcare system will be
faced with increased numbers of patients in this age group
presenting for management of seizures. The differential in this
age group is broad, and includes sleep disorder, syncope,
transient ischemic attack, transient global amnesia, metabolic
disturbances, and migraine. Compared to younger age groups,
seizures in the elderly are more likely to have an underlying
cause such as stroke and dementia, comorbidities that increase
the risk of mortality. While some data shows that the elderly

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Curr Geri Rep (2014) 3:7382

may be more likely to have recurrence following a first seizure, a full workup with an EEG and MRI of the brain should
still be obtained to better assess the need to start medications
and to search for structural lesions that could necessitate
further intervention.
When deciding on a treatment regimen for this age group, a
number of factors must be taken into account. Elderly are
more prone to side effects often requiring lower doses of
medications due to changes in hepatic metabolism, renal
clearance, and protein binding. Polypharmacy is common in
the elderly so drug-drug interactions and hepatic enzyme
induction or inhibition must also be considered. With regards
to these issues, the older antiepileptics such as phenytoin,
phenobarbital, carbamazepine and valproate can often be
problematic. Even newer medications such as oxcarbazepine
and topiramate can have worrisome side effects, such as
hyponatremia and cognitive slowing. Newer antiepileptic
medications that seem best tolerated in the elderly include
lamotrigine, levetiracetam, and gabapentin. While over twothirds of the elderly with epilepsy will respond to medications,
there will be treatment failures, and epilepsy surgery should be
considered in the healthy elderly as surgical outcomes appear
to be similar to their younger cohorts. Large randomized
control trials comparing newer medications such as levetiracetam, zonisamide, and lacosamide with the older antiepileptic
medications are lacking. Furthermore, there are no large controlled studies comparing specific medication treatment outcomes with seizure etiology (i.e., stroke, dementia, tumor).
Overall, as the elderly population grows, further research on
the medical and surgical management of epilepsy in this age
group is needed.

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3.

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7.

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14.

15.
Compliance with Ethics Guidelines
Conflict of Interest Cynthia M. Correll declares that she has no conflict
of interest.
Carl W. Bazil has received financial research support from Lundbeck
and Eisai.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.

16.

17.
18.
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20.

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