Recent Advances in Epilepsy Monotherapy: An Expert Interview

[Guest guest]

Thought some of you might find this interesting and helpful, came out of

recent American Epilepsy Conf about the effect of polytherapy, actually

worsening seizure disorders

Recent Advances in Epilepsy Monotherapy: An Expert Interview With

Gruenthal, MD, PhD

Disclosures

Priscilla Scherer, RN M.

Editor's Note: According to the Epilepsy Foundation, the US

prevalence of active epilepsy (defined as a history of epilepsy plus a

seizure or use of anticonvulsants within the last 5 years) is

approximately 2.5 million persons. Combination therapy with

antiepileptic drugs (AEDs) has been one approach to treatment for the

disease but is complicated by a number of issues. Monotherapy is,

however, the

preferred treatment option for epilepsy. Medscape interviewed

Gruenthal, MD, PhD, of the University of Louisville School of Medicine,

Louisville, Kentucky, about clinical advances in monotherapy and related

data from the December 2003 meeting of the American Epilepsy Society in

Boston,

Massachusetts.

Medscape: The goal of epilepsy monotherapy has become more attainable

in recent years. Aside from the obvious advantage of reduced pill

burden, what are the advantages of monotherapy in the patient with

epilepsy?

Dr. Gruenthal: Monotherapy in epilepsy has several distinct

advantages. The side-effect profile of a single drug is typically better

than that experienced with multiple drugs. This is especially true for

AEDs that have complex interactions with one another. The cost of

monotherapy is lower and compliance is

higher. Finally, the vast majority of patients who do not respond to

sequential monotherapy will not become seizure-free with polytherapy.

Medscape: Are there disadvantages to this treatment strategy?

Dr. Gruenthal: Monotherapy has no established disadvantages. There is

a theoretical disadvantage in that combinations of drugs with different

mechanisms could have additive or synergistic efficacy in preventing

seizures. Although there have been some anecdotal descriptions of good

responses to certain combinations, the possible benefits of this

approach have not been demonstrated in prospective,

controlled trials. Monotherapy remains the ideal approach.

Medscape: What are some of the major concerns when switching from an

existing combination regimen to monotherapy? Is there a " best " strategy

to follow?

Dr. Gruenthal: The biggest concern when switching from polytherapy to

monotherapy is that seizures will return or worsen. Available evidence

suggests that this is typically not the case. Although seizures may

briefly return during such a transition, they usually don't persist. If

they do, options include a return to

polytherapy, increasing the dose of the remaining AED, or trying

another AED as monotherapy. There is no " best " strategy. These decisions

are highly individualized and depend on epilepsy etiology or syndrome,

seizure frequency and patterns, history of exposure to other AEDs,

occupational issues, etc.

Sometimes patients are actually taking 1 or more drugs that are

inappropriate for their epilepsy syndrome. At best, these drugs are not

helpful, and at worst, they are actually increasing the seizure

frequency. In those instances, deciding what to eliminate is easy.

Otherwise, I usually begin by tapering the drug that appears to have had

the least benefit based on the patient's seizure diary. As with any

treatment decision in epilepsy, I believe it is essential to discuss

these issues with each patient and involve them in the decision-making

process.

Medscape: Are there any other considerations when choosing a

particular agent, particularly among specific populations, such as the

elderly or women of childbearing age?

Dr. Gruenthal: Absolutely. These are very important considerations.

Because the number of treatment options has increased in the past

decade, we are in a much better position to tailor treatment to specific

patient populations and to a patient's individual circumstances. This

may be the single greatest benefit of the newer AEDs. Since these

decisions require a detailed understanding of the unique characteristics

of a growing armamentarium of treatment options, patients may be best

served by an evaluation at a center specializing in epilepsy diagnosis

and treatment.

Medscape: At the American Epilepsy Society (AES) meeting, is the body

of data on epilepsy monotherapy represented well enough to give the

general neurologist or primary care practitioner an update on current

practices?

Dr. Gruenthal: The annual meeting of the AES is one of the most

exciting meetings for me. There is an intense energy generated by the

high caliber of presentations and the " cutting-edge " content. Because

much of the information is new and at times quite preliminary, I don't

think it's the best venue for general-practice providers to gather

information about current practices, but most general neurologists

who care for patients with epilepsy can glean clinically useful and

relevant information from the meeting.

Medscape: Can you tell us about the study you reported at this year's

AES meeting and its practical significance?

Dr. Gruenthal: In conjunction with my colleagues at the University of

Louisville School of Dentistry, I presented data from a study we

designed to test the hypothesis that phenytoin-induced gingival

hyperplasia in institutionalized patients could be reversed by tapering

phenytoin and substituting topiramate.[1] We observed a substantial

improvement in measures of periodontal health. The practical

significance is that the newer drugs often provide effective

alternatives to the older drugs and have fewer side effects.

Medscape: Could you comment on a few of the studies of monotherapy in

newly diagnosed patients?

Dr. Gruenthal: Until recently, most of the newer drugs had been

evaluated in patients with longstanding, refractory epilepsy. Attention

is now shifting to other patient populations, including those with newly

diagnosed epilepsy. This may be particularly important in light of

findings reported by Ficker and

colleagues.[2] Their preliminary data suggest that side effects from

medication may be the most important determinant of poor health-related

quality of life in people with newly diagnosed epilepsy.

Since many of the newer drugs appear to have better side-effect

profiles than older drugs, they may provide advantages as long as they

are also effective in preventing seizures. Wheless[3] and Rho[4]

reported that topiramate was effective in prolonging the time to the

first seizure after study entry in a group of previously untreated

adults and children with either partial-onset or primary generalized

tonic-clonic seizures. Christe and others[5] studied the efficacy and

side-effect profiles of oxcarbazepine and valproate in patients with

newly diagnosed epilepsy. After 1 year there were no differences in

efficacy, but patient ratings of tolerability favored oxcarbazepine.

Medscape: What other presentations on monotherapy -- or other

therapeutic strategies -- do you think were particularly noteworthy at

the AES meeting?

Dr. Gruenthal: I was very intrigued by a presentation from Taoufik

Alsaadi and colleagues[6] from the University of California at .

They described data from a study in which patients with medically

refractory epilepsy were converted from polytherapy to monotherapy. As

expected, they found significant improvements in quality-of-life

measures. Most interestingly, they also found that many patients

experienced an improvement in seizure control after conversion from

polytherapy to monotherapy. This was a small retrosp ective study, so

there are many possible explanations for their observations.

Nevertheless, it seems to reinforce the notion of monotherapy and

raises questions about under what circumstances polytherapy might be

justified.

In our epilepsy program at the University of Louisville, we often see

patients who have had drugs added over the years in an effort to improve

seizure control. Unfortunately, in most instances little attention was

given to simultaneously eliminating the drugs that weren't working in

the first place. I think we need to be

aggressive in our efforts to achieve complete seizure control, but

this study highlights the point that sequential monotherapy may make

more sense than polytherapy.

Disclosure: Gruenthal, MD, PhD, has disclosed that he has

received grants for preclinical research from Ortho-McNeil He has

received grants for educational activities from GlaxoKline. Dr.

Gruenthal has served as an advisor or consultant for GlaxoKline,

Pfizer, and Novartis. Dr. Gruenthal

has reported that he does not discuss any investigational or

unlabeled uses of commercial products in this activity.

References

1.Gruenthal M, Hood HD, Crone A, Farman AG. Conversion from

phenytoin to topiramate: an

open-label evaluation of periodontal outcome in

institutionalized patients with phenytoin-induced

gingival hyperplasia. Epilepsia. 2003;44(suppl 9):277[Abstract

2.296].

2.Ficker DM, C, Shukla R, Privitera MD. Determinants of

health-related quality of life in

newly diagnosed seizures. Epilepsia. 2003;44(suppl

9):182[Abstract 2.020].

3.Wheless JW, Arroyo S, Squires L, Twyman RE, Wang S. Topiramate

as first-line therapy in newly

diagnosed epilepsy characterized by partial-onset or primary

generalized tonic-clonic seizures.

Epilepsia. 2003;44(suppl 9):273[Abstract 2.284].

4.Rho JM, Arroyo S, Squires L, Wang S, s D. Topiramate as

first-line therapy: findings from

children and adolescents with newly diagnosed epilepsy.

Epilepsia. 2003;44(suppl

9):93[Abstract 1.261].

5.Christe W, Sfikas N, M. Oxcarbazepine is at least as

effective and better tolerated than

valproate for long-term treatment in newly diagnosed patients

with epilepsy. Epilepsia.

2003;44(suppl 9):265[Abstract 2.259].

6. SP, Farias SE, Lima AR, Alsaadi TM. Improvement in

seizure control and quality of life

in medically refractory epilepsy patients converted from

polypharmacy to monotherapy. Epilepsia.

2003;44(suppl 9):270[Abstract 2.274].