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Breakthrough Seizures—Approach to Prevention and Diagnosis
potentially devastating ramifications for patients with epilepsy. There is
Table 1: Drugs That May Lower the Seizure Threshold
also a chance that patients simply do not fully understand the nature of
the treatment and the importance of remaining adherent; if a patient Category Drug
happens to have a long period in which he or she is seizure-free in the
Antiasthmatics Aminophylline
face of non-adherence, that patient may be lulled into a false sense of
Theophylline
confidence that skipping medications will have minimal consequences.
Antibiotics Isoniazid
Lindane
Metronidazole
What are the consequences associated with breakthrough
Nalidixic acid
seizures related to non-adherence?
Penicillins
In addition to the risk for injury requiring hospitalization and monitoring,
Antidepressants Bupropion
there are significant effects on economic costs and mortality. We utilized
Tricyclics
data from the Integrated Health Care Information Services in a
Serotonin-specific agents
retrospective analysis examining the prevalence and cost impact of General anesthetics Enfluraneketamine
non-adherence in an elderly population aged 65 years and over with Hormones Estrogen
epilepsy.
1
Adherence was evaluated using the medication possession
Insulin
ratio (MPR), a standard accepted analysis tool that estimates the ratio of
Oxytocin
total days supplied of a medication over the days between AED refills. An
Prednisone
MPR ratio greater than or equal to 0.8 is traditionally used as the cut-off
Immunosuppressants Chlorambucil
Cyclosporine a
designating good adherence, with a ratio lower than 0.8 as non-
Local anesthetics Bupivicaine
adherence. The results of the study were very worrying, in that nearly
Lidocaine
41% of the patients studied had an MPR ratio less than 0.8—meaning
Procaine
that virtually half of the patient population had poor adherence. This
Narcotics Fentanyl
non-adherence was also strongly correlated to the occurrence of serious
Meperidine
seizures, which led to an overall increase in the number of visits to the Pentazocine
physician’s office, emergency department, and hospital. There was also a Propoxyphene
substantial increase in the risk for hospitalization, which resulted in
Psychostimulants Amphetamines
escalated costs of approximately $2,400 per patient as a result of the
Cocaine
additional interventions that were needed because of non-adherence.
Methylphenidate
These statistics may even be an under-representation of the problems
Phenylpropanolamine
Neuroleptics Clozapine
associated with suboptimal adherence in epilepsy patients, because it is
Butyrophenones
conceivable that some patients, even in the face of a major seizure, did
Phenothiazines
not seek additional care from hospitals.
Other Anticholinergics
Anticholinesterases
The risks associated with AED non-adherence have also been graphically
Antihistamines
demonstrated in the recently published Research on Antiepileptic Non- Baclofen
adherence and Selected Outcomes in Medicaid (RANSOM) study.
2
This Heavy metals
retrospective examination of Medicaid data studied the AED adherence of
Hyperbaric oxygen
epilepsy patients aged 18 years and over utilizing the MPR, and found an
Lithium
association between periods of non-adherence and significantly higher
Mefenamic acid
incidence of visits to emergency departments, hospitalizations, fractures,
Oral hypoglycemics
and injuries related to motor vehicle accidents compared with periods of
Adapted from Koppel BS, Contribution of drugs and drug interactions (prescribed, over the
counter, and illicit) to seizures and epilepsy. In: Ettinger AB, Devinsky O (eds), Managing epilepsy
adherence. Furthermore, patients non-adherent to AEDs exhibited a three- and co-existing disorders, Boston: Butterworth-Heinemann, 2002;155–173.
fold increased risk for mortality compared with adherent patients.
patient and warn of potential side effects, as well as the need to contact
What would you recommend in order to reduce the the physician before autonomously discontinuing the medication.
occurrence of breakthrough seizures?
It is intuitive that the selection of an AED would be based primarily In terms of reducing the occurrence of breakthrough seizures due to
on efficacy, and many of the available agents are quite comparable in non-adherence, there are strategies that clinicians can use to improve
their efficacy. However, there are other factors that the clinician should patient adherence. Among these are greater efforts in promoting a better
consider when selecting the optimal AED, such as potential side effects, physician–patient relationship and taking the time to ensure that patients
ease and frequency of administration, cost-effectiveness, and drug understand why the medications are required, what the nature of the
interactions. I would encourage any clinician prescribing an AED to dosing is, potential drug interactions, and possible side effects. Providing
review the side effects commonly associated with AEDs overall, as well as instructions and information in a written format can also be useful.
the potential side effects specific to each individual agent being
considered. By familiarizing themselves with the drug information, Communication obviously plays a big role. It is important to avoid the
clinicians will be better able to review the drug characteristics with the technical medical terms that we physicians are often inclined to use, and
US NEUROLOGY 41
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