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12 - Central Nervous System Disorders |
357
ment of first choice for generalized seizures,
and, for generalized tonic-clonic seizures refrac-
tory to treatment, adjunctive therapy with topi-
ramate is recommended based on safety and
efficacy data.
93
The SANAD Study Group trials were large,
open-label trials designed to best reflect clinical
practice in that providers were able to change
agents if it was deemed there was treatment
failure or intolerability.
96,97
There were two arms
of the study: one for the treatment of partial
epilepsy and another for the treatment of gener-
alized or otherwise unclassified epilepsy.
96,97
In
the first arm, investigators studied carbamaze-
pine, gabapentin, lamotrigine, oxcarbazepine,
and topiramate as monotherapy for the treatment
of new-onset partial epilepsy. The majority of the
individuals randomized had never received a
prior therapy. The median age was 38.3 years
old, and the time to treatment failure (defined
as stopping of the medication because of either
intolerable side effects or inadequate seizure
control) was statistically significantly better in the
group receiving lamotrigine, with carbamaze-
pine and oxcarbazepine both having statistically
significant results as well. In the time to 12-month
remission, another primary endpoint, lamotrigine
was found to be noninferior to carbamazepine.
97
In the second arm of SANAD, individuals with
generalized or otherwise unclassified epilepsy
were randomized to either valproate, lamotrigine,
or topiramate. Valproate showed superiority
in both primary endpoints of time to treatment
failure (defined as above) and time to 12-month
remission.
97
However, the median age in the B
arm of SANAD was 22.5 years.
In 2008, the FDA completed an analysis of
trials in which AEDs were compared to placebo
for a variety of conditions (e.g., epilepsy, psychi-
atric disorders, migraines) and determined an
increased risk of suicidal thoughts and behav-
iors was associated with treatment with an AED.
Warnings are now included in the package
labeling to this effect, and a Medication Guide
is required to be given with each dispensation of
an AED, for any indication.
Review of Evidence Supporting
Treatment Recommendations in the
Elderly
The goals of therapy for a senior patient are no
different than those for younger patients, with an
additional goal of minimizing drug interactions,
because of the increased number of medica-
tions seniors typically take. Seniors are typically
excluded from trials of AEDs, as is the case with
many disease states despite the fact that those
over age 60 account for 25% of new cases of
epilepsy.
98
The exclusion of seniors from trials
is due to their high number of comorbid condi-
tions and, thus, medications taken, as well as the
increased risk of side effects that could impact
safety data presented. Even when they are
included in trials of seizure medications, criteria
often eliminate those with severe chronic disease
(which is typically ill-defined in the literature),
psychiatric disease, other neurological illnesses,
and even those who are receiving medica-
tions known to interact with the agent being
researched. A prime example is a study done to
assess the tolerability and safety of oxcarbaze-
pine, which utilized the pharmaceutical com-
pany’s database.
99
Of 1,626 patients in oxcar-
bazepine trials, 52 (3.2%) were older than 65,
and 18 (1.1%) were older than 75. Trials involving
the senior population are often small, open-label,
prospective, single-center trials, limiting the
ability to apply the results to the general senior
population. The few agents that have looked
at efficacy, safety, and quality-of-life measures
specifically in the elderly are lamotrigine, carba-
mazepine, topiramate, oxcarbazepine, and leve-
tiracetam.
By far, the most widely researched AED
in the elderly is lamotrigine. It has shown effi-
cacy as both monotherapy and in combination
with other therapies, as well as better toler-
ability when compared to other therapies, most
notably carbamazepine.
100-104
Most trials are
in elderly patients with any type of seizure, but
lamotrigine was studied specifically in those who
had an ischemic stroke and developed seizures,
and although it was a small study, there was no
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| Fundamentals of Geriatric Pharmacotherapy
Table 12-7. Seizure Medications: Indications and Common Dosages
Agent
Seizure-Related Indications
a
Common Daily Dosages
b
Carbamazepine Partial seizures with complex symptomatology
Generalized tonic-clonic
Mixed seizure patterns
Monotherapy for newly diagnosed
800–1,200 mg/day
c
Ezogabine Adjunct for partial-onset seizures 300–900 mg/day
c
Felbamate Monotherapy or adjunctive therapy for partial
seizures ± secondary generalization
d
2,400–3,000 mg/day
c
Fosphenytoin Control of generalized SE
Prevention and treatment of seizures during
neurosurgery
SE: loading dose 15–20 mg PE/kg with
a rate of 100–150 mg PE/min
Nonemergent: loading dose
10–20 mg PE/kg IV or IM
Maintenance dose 4–6 mg PE/kg/day
IV or IM
c
Gabapentin Adjunct for partial seizures ± secondary
generalization
Monotherapy for newly diagnosed
Add-on for refractory epilepsy
900–2,400 mg/day
c
Adjust dose for renal insufficiency
Lacosamide Adjunctive therapy for partial onset seizures 200–400 mg/day
c
Adjust dose for renal insufficiency
Lamotrigine Adjunctive for primary generalized tonic-clonic
Adjunctive for partial seizures
Monotherapy for newly diagnosed
Mono- or add-on therapy for refractory epilepsy
(although evidence for monotherapy in this
setting is weaker)
225–375 mg/day
c
Regimens with valproic acid:
100–400 mg/day
c
Regimens with an enzyme-inducing
AED: 300–500 mg/day
c
Adjust dose for renal insufficiency
Levetiracetam Adjunctive therapy for partial seizures
Adjunctive therapy for myoclonic and/or
primary generalized tonic-clonic
Add-on for refractory epilepsy
2,000–3,000 mg/day
c
Adjust dose for renal insufficiency
Oxcarbazepine Monotherapy or adjunctive therapy for partial
seizures
Monotherapy for newly diagnosed
Mono- or add-on therapy for refractory epilepsy
1,200–2,400 mg/day
c
Perampanel Adjunct for partial seizures 8–12 mg/day
Phenobarbital Management of generalized tonic-clonic
Management of partial seizures
Monotherapy for newly diagnosed
100–300 mg/day
c
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Table 12-7. Seizure Medications: Indications and Common Dosages (continued)
Agent
Seizure-Related Indications
a
Common Daily Dosages
b
Phenytoin Management of generalized tonic-clonic seizures
Management of complex partial seizures
Seizure prevention in head trauma/neurosurgery
Monotherapy for newly diagnosed
300–1,200 mg/day
c
Pregabalin Adjunctive therapy for partial seizures 150–600 mg/day
c
Adjust dose for renal insufficiency
Primidone Management of grand mal, psychomotor, or focal
seizures
750–1,500 mg/day
c
Rufinamide No adult indications at present. 1,600–3,200 mg/day
c
Topiramate Monotherapy or adjunctive therapy for partial
seizures
Monotherapy or adjunctive therapy for tonic-
clonic
Monotherapy for newly diagnosed
Mono- or add-on therapy for refractory epilepsy
Monotherapy: 100–400 mg/day
c
Adjunctive partial: 100–200 mg bid
Adjunctive tonic-clonic: 200 mg bid
Tiagabine Adjunctive therapy for partial seizures
Add-on for refractory epilepsy
Regimens with enzyme-inducing
AEDs: 32–56 mg/day
c
Valproic acid Monotherapy or adjunctive therapy for complex
partial seizures
Monotherapy or adjunctive therapy for simple or
complex absence seizures
Monotherapy for newly diagnosed
15–60 mg/kg/day
c
Vigabatrin Refractory, complex partial seizures 1,000–3,000 mg/day
c
Zonisamide Adjunctive therapy for partial seizures
Add-on for refractory epilepsy
100–400 mg/day
c
IM, intramuscular; IV, intravenous; PE, phenytoin equivalents; SE, status epilepticus.
a
Indications applicable to older adults.
b
Indicates common total daily dosages.
c
In divided doses.
d
Not indicated for first-line therapy.
See reference 128 for additional information.
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| Fundamentals of Geriatric Pharmacotherapy
difference in seizure frequency with lamotrigine
versus carbamazepine.
104
However, there was
increased tolerability with lamotrigine. Carbam-
azepine in these trials, although less tolerable
than lamotrigine in this population, was noted
to be efficacious for seizures in the elderly. A
small, open-label study of patients aged 60
and older who wished to change AED, either
because of intolerable side effects or continuing
seizures, were given a trial of lamotrigine first as
add-on therapy and then as monotherapy, if they
wished.
102
In those patients who chose to convert
to lamotrigine monotherapy, 64% achieved
seizure freedom. And, in an analysis of over 400
patients over the age of 55, lamotrigine was the
most effective at decreasing seizure frequency
and showed the best tolerability profile when
compared to 10 other antiepileptic medica-
tions.
105
Topiramate has some data to support its use
as monotherapy in the elderly in a small trial and
a subgroup analysis of a larger seizure trial.
106,107
Both showed similar efficacy to trials in younger
patients, with seizure freedom ranging from 63%
at 7 months and 44% at 12 months.
106,107
Adverse
effects were dizziness, nausea, loss of appetite,
and paresthesias. Of note, there was a statisti-
cally and clinically significant decrease in weight
from baseline in one of the trials.
107
A small subgroup of elderly patients within
a larger clinical trial of oxcarbazepine as
monotherapy for partial seizures showed good
response in the 12-month remission rates among
the seniors in the cohort (n = 19).
108
There was
no breakdown within the subgroup in regard
to adverse events. However, a retrospective
analysis of the elderly patients within a large
database of trials of oxcarbazepine as mono-
therapy showed similar safety and tolerability
with oxcarbazepine compared to the remainder
of the cohort, although the number of seniors
was small.
99
Hyponatremia, vertigo, nausea,
and abnormal vision were more common in the
elderly than in the younger drop-outs. This anal-
ysis did not assess efficacy.
A small study of levetiracetam monotherapy
in poststroke patients with at least two seizures
showed seizure freedom at 4 months in 85%. One
person discontinued treatment due to intolerable
somnolence.
109
A retrospective chart review of
elderly patients with partial epilepsy receiving
levetiracetam noted good response and rela-
tively good tolerability,
110
and in a retrospective
chart-review of over 400 patients, levetiracetam
showed good efficacy in decreasing seizures,
as well as good tolerability in the elderly with
new onset seizures.
105
In an observational study
of Alzheimer patients with new-onset seizures,
a trial of levetiracetam was given after removal
of all medications that could increase risk of
seizures, including their CI and any neuroleptic
they were receiving.
111
At a dose of 1,000−1,500
mg/day, levetiracetam was associated with
seizure freedom in 18 of the 25 patients; 4
patients discontinued the drug because of intol-
erable side effects, including somnolence, gait
disturbance, agitation, and increased confusion.
However, it is unclear whether discontinuation of
other therapies could have confounded these
adverse events.
Many trials of AEDs look specifically at toler-
ability in the elderly population, relying on effi-
cacy data from the younger cohort. However,
given the differing etiologies of seizures in the
senior population, this extrapolation of data
should be done with caution. Elderly patients
also tend to achieve seizure control with lower
doses of AEDs and at lower AED serum levels
than younger people.
112
This begs the question
of whether serum monitoring should be done in
an elderly patient if lower AED serum levels are
effective. A position paper by the ILAE Commis-
sion on Therapeutic Strategies suggests thera-
peutic drug monitoring in the elderly after a
newly-started AED has reached steady state to
determine the individual’s therapeutic concen-
tration. They also recommend therapeutic drug
monitoring when doses of interacting medica-
tions are being adjusted. The ILAE also support
measuring the unbound concentrations of AEDs
known to be highly protein-bound.
113
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361
KEY POINT:
Because of the
potential for low albumin in the
elderly, it is appropriate to measure
unbound concentrations of highly
protein-bound AEDs.
The treatment of status epilepticus in the
elderly typically follows that of the general
population. No specific evidence supporting or
refuting current guidelines in the elderly subpop-
ulation exists.
There is currently no evidence to suggest an
increase in suicidal behaviors or thoughts specif-
ically in the elderly, and given the low numbers
of elderly in trials of these agents, conclusions
are not likely to be drawn. However, the FDA’s
new warnings and the receipt of a Medication
Guide with each AED prescription include those
dispensed to seniors.
Common Problems Encountered in
the Senior Population with Seizure
Disorder
A common clinical problem in the care of the
older adult is encountering the prescription of an
AED prescribed in the poststroke period. Ques-
tions can arise regarding the necessity of a long-
term AED, as well as whether it is appropriate
or not if the patient only had one seizure after
the stroke. The incidence of poststroke epilepsy
is 5% to 15%,
114-116
and most major societies
advise against primary prophylaxis for seizures
in the poststroke period.
117,118
However, when a
senior has a seizure, the risk of a second seizure
depends on when the seizure occurred. For
those seniors with an early-onset seizure (within
7 days of the stroke, but typically within 24
hours), the incidence of another seizure is less
than 43%.
119
However, in those with late-onset
seizures (more than 7 days after the stroke), the
potential for a second seizure can range from
50% to 60%.
119
Because of this increased risk,
many clinicians will choose to provide long-term
secondary prophylaxis. It is important to note
that there is scant data to support this prac-
tice, and typically if a senior is put on this type
of prophylaxis, he or she will likely be on it for
the long term. The patient would then need to
be seizure-free for 2–5 years and have a normal
EEG to be considered for withdrawal of the AED.
The choice of whether to provide prophylaxis or
not should be done in concert with the patient or
his or her caregiver, weighing the risks of an AED
alongside the risk of another seizure.
Seniors, high consumers of healthcare,
can be more prone to the drug interactions and
untoward side effects of AEDs. The pharmaco-
kinetic and pharmacodynamic changes asso-
ciated with aging also make the choice of AED
somewhat difficult. Whereas many newer-gener-
ation AEDs tend to be better tolerated, the cost
associated with the agents themselves can be a
limiting factor to their use in the senior population.
Agent-Related
Despite being used frequently in the elderly with
seizure disorder, phenytoin has many issues
associated with its use, especially long term. It
induces many CYP450 isoenzymes, making it
highly likely to interact with many common medi-
cations used in the elderly, and decrease blood
levels of common vitamins, such as B6, B12,
and vitamin D.
120
When given concomitantly with
tube feedings, its bioavailability is significantly
reduced, putting patients at risk for lower blood
levels and also increased risk for seizures. Tube
feedings should be stopped for 2 hours prior to
phenytoin administration and should be held for
at least 1 hour after phenytoin administration.
This can be very difficult in someone receiving
twice-daily administration of phenytoin on contin-
uous tube feeds, and in most cases if this cannot
be done easily, switching to another AED is often
employed. However, in those whom phenytoin is
unable to be stopped, doses may be increased
to compensate for this interaction. However, it is
of the utmost importance to be consistent with
dosing and to remember dosage adjustments
have been made should the tube feeding be
stopped for any length of time or discontinued.
Phenytoin can increase the risk for falls by both
inducing vitamin D metabolism, as well as the
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| Fundamentals of Geriatric Pharmacotherapy
potential to cause cerebellar atrophy with long-
term use. In order to assess true steady state,
levels should be drawn 2–3 weeks after starting
phenytoin in the elderly because of increased
half-life in this population. And because it is
highly protein bound, a free phenytoin level
should be drawn in a frail elderly patient who is
likely to have hypoalbuminemia, rather than a
total phenytoin assay.
Phenytoin can block alpha-receptors
and, thereby, may decrease internal bladder
sphincter tone, which can exacerbate stress
urinary incontinence. The gingival hyperplasia
seen in a younger cohort is not typically seen in
the elderly. Fosphenytoin has very little research
specifically in the elderly; however, its ability to
induce many P450 isoenzymes makes its use in
the elderly difficult. But it is typically only used
short term in emergent situations, or when the
oral route of administration is not available in a
patient receiving phenytoin.
KEY POINT: If phenytoin doses are
increased to compensate for decreased
absorption because of tube feedings, it
is of utmost importance to be consistent
with dosing and to remember doses have
been adjusted if tube feedings are stopped
for any length of time or discontinued.
Hyponatremia, rash, and syndrome of
inappropriate secretion of antidiuretic hormone
are side effects that can occur with carba-
mazepine; however, they can be seen with
increased frequency in the elderly.
91
Because
of its induction of many CYP450 isoenzymes,
carbamazepine is highly likely to interact with
many medications commonly found on the
profiles of elderly patients. Carbamazepine also
induces its own metabolism. It binds to alpha-
glycoprotein (known to increase in the elderly),
which can make total carbamazepine levels look
falsely therapeutic. Carbamazepine can induce
vitamin D metabolism, potentially leading to an
increased risk of osteoporosis and falls. Over-
flow incontinence, secondary to increased para-
sympathetic stimulation of the detrusor, is also
an untoward consequence of carbamazepine
use commonly overlooked.
91
Similar to carbam-
azepine, oxcarbazepine has an increased risk
of hyponatremia in the elderly and can decrease
the efficacy of estrogen, something to note in
an individual receiving estrogen-replacement
therapy. Oxcarbazepine also has evidence
to suggest an increased risk of MI and stroke
compared to carbamazepine.
121
Valproic acid is commonly used in elderly
patients. Its time to steady state may be doubled
in an elderly cohort, so this should be taken into
consideration for drug monitoring. Platelet count
and ammonia levels should be monitored and,
in those with hypoalbuminemia, the unbound
concentration should be tested. Weight gain
and a fine hand tremor may also be seen in the
elderly receiving valproic acid.
Phenobarbital, another older agent, should
be used in the elderly with extreme caution, if
at all, because of its long half-life and ability to
cause cognitive disturbances. It can also inter-
fere with vitamin D metabolism and is highly
protein bound, which can be an issue in an elderly
patient with decreased albumin. Like oxcar-
bazepine, there is some evidence to support an
increased risk of MI and stroke with phenobar-
bital when compared to carbamazepine.
121
Due
to additive respiratory depression, phenobarbital
is contraindicated with the concomitant use of
an opioid. It is noted as a drug to be avoided in
the elderly and is associated with dependence.
Primidone, the parent drug of phenobarbital, has
the same issues and warnings. When discon-
tinuing these agents, doses should be tapered
slowly to avoid withdrawal reactions.
Gabapentin’s ability to cause weight gain
is well documented in the literature in the young
and is also seen in the elderly in clinical prac-
tice. Elderly are much more prone to the effects
of ataxia and somnolence, however. Gaba-
pentin has the potential to cause edema, yet is
commonly overlooked when iatrogenic causes
are being investigated. Pregabalin has a similar
side effect profile.
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Lamotrigine is well known for the potential to
cause a rash, which can occur at any time during
its use, but most often is seen in the titration
phase. A Stevens-Johnson syndrome–type rash
may also occur in patients taking lamotrigine;
therefore, any complaint of rash needs to be
quickly addressed, given the life-threatening
nature of this particular syndrome. This risk for
rash is increased in those receiving concomitant
valproic acid. However, with slow titration, over
more than 8 weeks, this adverse effect can be
minimized. This need for slow titration limits its
use to those who do not need immediate thera-
peutic doses of their seizure medication.
Levetiracetam’s literature support in the
elderly has been growing in recent years. This
is owed in large part to very few drug interac-
tions, no protein-binding, and a perception of a
mild side effect profile, compared to other AEDs.
This has largely been supported in clinical trials.
However, levetiracetam must be dose-decreased
in renal dysfunction and, like the other AEDs, has
growing evidence of the potential to contribute
to low bone mineral density. Topiramate’s most
common side effect in the elderly is weight loss.
On average, in small clinical trials in the elderly,
patients lost ~5 pounds, with a subgroup anal-
ysis noting those with an increased body mass
index (BMI) losing the most weight.
106,107
Cogni-
tive disturbance and word-finding difficulties can
be experienced in the elderly on topiramate. In
younger patients, topiramate has an increased
risk of kidney stones, which should be monitored
in the elderly, especially those with decreased
water intake or on water restriction due to other
disease states, such as congestive heart failure.
Zonisamide is rarely used in the elderly, for
several reasons. It should be used with caution
in those with a creatinine clearance <50 mL/min
and in those allergic to sulfonamides. Zonisamide
may also increase the risk of renal stones, so
like topiramate it should be used with caution in
those with low water intake. Zonisamide has also
been implicated in causing cognitive impairment
and psychosis as well as increasing the chance
of metabolic acidosis.
Several AEDs have not been evaluated in
older adults. Ezogabine has not been evaluated
in the elderly, but because of issues with eye
abnormalities, sometimes leading to vision loss
and blue-skin pigment changes, this will likely
remain a last-line adjunctive agent. Ezogabine
can also cause urinary retention, hallucinations,
and QT prolongation, which can be problematic
in an elder. Lacosamide should be used with
caution in those with conduction disorders as
it has the potential to prolong the PR interval. It
should be avoided in those with congestive heart
failure and in those who are taking other medi-
cations that prolong this interval. Perampanel
can cause significant neuropsychiatric issues,
including agitation and aggression, as well as
gait disturbances and dizziness. Rufinamide is
indicated only as adjuvant therapy for general-
ized seizures secondary to Lennox-Gastaut, a
type of epilepsy seen in children. It can shorten
the QT interval and must be used with caution
in those patients with pre-existing conduc-
tion disorders and in those on concomitant QT
interval shortening medications. Tiagabine can
result in Stevens-Johnson syndrome or toxic
epidermal necrosis, albeit rarely, as well as
cognitive slowing. It is also highly protein bound,
so free concentration should be measured if
therapeutic drug monitoring is undertaken. Viga-
batrin’s boxed warning regarding permanent
vision loss in up to a third of people who take the
drug is the rationale behind its use only in refrac-
tory cases of complex partial seizure disorder. It
can also cause issues with psychosis, peripheral
edema, and anemia.
As with any pharmacotherapeutic interven-
tion, the medication cannot work if the patient
does not take it, and adherence to the AEDs can
be difficult in the elderly. Two risk factors have
been elucidated in the literature that increase
the likelihood of nonadherence to AEDs by the
elderly: impairment of cognitive function and
weight gain.
122
The incidence of these side
effects should definitely be taken into account
when starting a new AED in an elderly patient as
well as when nonadherence is suspected.
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| Fundamentals of Geriatric Pharmacotherapy
Disease-Related
Many medications and herbal products
commonly used by the geriatric population
may lower seizure threshold (see Table 12-8). It
is important to avoid the use of these medica-
tions whenever possible in a patient with seizure
disorder. If a patient should have a new onset
seizure, a thorough medication review should
take place, ensuring the patient is asked about
over-the-counter product use as well as herbals.
Certain AEDs are excreted by the kidneys.
Dose adjustments are frequently required in
elderly patients because of renal insufficiency.
Table 12-7 notes the agents that necessitate this
modification.
Table 12-8. Medications and Dietary
Supplements That Decrease Seizure
Threshold
Bupropion Lithium
Cephalosporins Ma huang
Cholinesterase inhibitors Maprotiline
Duloxetine Meperidine
Ephedrine Memantine
Fluoroquinolones Metoclopramide
Fluvoxamine Penicillins
Ginkgo biloba Phenothiazines
Ginseng St. John’s wort
Insulin Theophylline
Isoniazid Tramadol
Kava kava Tricyclic
antidepressants
Venlafaxine
See reference 91 for additional information.
Several enzyme-inducing AEDs have been
implicated in the literature as increasing the risk
of osteoporosis. However, there is emerging
evidence that this might be a class effect.
123
Regardless of the cause of decreased bone
mineral density (BMD) or osteoporosis, this
decreased bone strength should be treated.
Although there is no FDA-approved agent for the
treatment of AED-induced osteoporosis, a small
trial of male veterans receiving AED therapy
(average age, 60.5 years) noted a statistically
significant increase in BMD at the lumbar spine
with the use of risedronate 35 mg orally once
weekly when added to a regimen of calcium
and vitamin D, compared to those receiving
just calcium and vitamin D alone.
124
However, it
should be noted that there were also BMD gains
in those on calcium and vitamin D alone, only
more so in the group receiving additional risedro-
nate. For patients using an AED known to induce
vitamin D metabolism, it is a prudent recommen-
dation to follow 25-OH vitamin D levels regu-
larly and supplement if necessary. Patients with
seizures should be screened on a regular basis
for depression and anxiety, as these conditions
can be seen with increased incidence in those
with seizure disorder.
125
Again, the choice of
agent should be chosen with patient- and agent-
related variables in mind. Table 12-9 provides
other drug-disease interactions to consider
when choosing an AED.
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Table 12-9. Antiepileptic Drug-Disease Interactions
Selected Conditions
a
Precaution Contraindication
Anorexia, weight loss Felbamate, topiramate, carbamazepine (anorexia),
rufinamide, zonisamide (anorexia)
Cardiac conduction
abnormalities, ventricular
arrhythmia
Carbamazepine, ezogabine, fosphenytoin,
lacosamide, lamotrigine, phenytoin (parenteral),
oxcarbazepine
Phenytoin if sinus
bradycardia, sinoatrial
block, 2nd-or
3rd-degree AV block,
Adams-Stokes block
Rufinamide if familial
short QT syndrome
Cognitive impairment Barbiturates,
b
benzodiazepines, topiramate,
tiagabine, zonisamide
Gait unsteadiness,
dizziness
Barbiturates, carbamazepine,
c
felbamate,
gabapentin, lacosamide, lamotrigine,
levetiracetam, oxcarbazepine, perampanel,
phenytoin, pregabalin, rufinamide, tiagabine,
topiramate, valproate,
c
zonisamide
Hepatic disease,
impairment
Carbamazepine, ezogabine, felbamate, lacosamide,
rufinamide, tiagabine, valproate, zonisamide,
oxcarbazepine, perampanel, phenytoin
Felbamate,
phenobarbital,
valproate
Hyponatremia Carbamazepine, oxcarbazepine
Narrow-angle glaucoma Topiramate Gabapentin
Osteomalacia, osteoporosis
d
Carbamazepine, levetiracetam, oxcarbazepine,
phenobarbital, phenytoin, primidone, valproate
Respiratory disease
(obstructive, dyspnea)
Benzodiazepines, phenytoin (IV, IM) Phenobarbital
Tremor (familial, Parkinson
disease)
Gabapentin, lacosamide, lamotrigine, pregabalin,
rufinamide, tiagabine, topiramate, valproate
Renal impairment Ezogabine, gabapentin, lacosamide, levetiracetam,
perampanel, phenobarbital, pregabalin, topiramate,
vigabatrin, zonisamide
Sedation Barbiturates, benzodiazepines, carbamazepine,
felbamate, gabapentin, lacosamide, lamotrigine,
pregabalin, oxcarbazepine, rufinamide, tiagabine,
topiramate, valproate
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| Fundamentals of Geriatric Pharmacotherapy
Table 12-9. Antiepileptic Drug-Disease Interactions (continued)
Selected Conditions
a
Precaution Contraindication
Urinary incontinence Carbamazepine, clonazepam, ezogabine,
gabapentin, lamotrigine, oxcarbazepine,
phenobarbital, phenytoin, tiagabine, topiramate,
valproate
Nephrolithiasis Topiramate, zonisamide
AV block, atrioventricular nodal block; IM, intramuscular; IV, intravenous.
a
Hypersensitivity to the antiepileptic drug, its ingredients, or related class of drugs is a contraindication.
b
Phenobarbital is commonly believed to impair cognition; however, at equivalent serum drug concentrations, this effect was no different
than antiepileptic drugs with an uncertain effect (phenytoin, carbamazepine, oxcarbazepine, valproate).
c
Carbamazepine and valproate may pose a lower risk of gait disturbance than other antiepileptic drugs.
d
The risk of osteoporosis with several of the newer antiepileptic drugs is not established.
Source: Adapted with permission of John Wiley from Lackner TE. Strategies for optimizing antiepileptic drug therapy in elderly people.
Pharmacotherapy. 2002;22:329–364; permission conveyed through Copyright Clearance Center, Inc.
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