Drug Interaction

Drug Interaction Study of Tegretol Carbamazepine and St Johns Wort in Normal Volunteers

To their regular medicines to elevate mood or relieve stress. Preliminary research indicates that this supplement can speed the metabolism of the anti-seizure drug Tegretol, causing reduced blood levels of the drug. Patients who take Tegretol to control their seizures may have more frequent seizures if the blood level of the drug drops too low. A recent study shows that this effect is not seen when Tegretol is taken for at least 3 weeks. The present study will examine whether there is a medically important drug interaction between St. John's wort and Tegretol when Tegretol is taken for 1 day. Normal healthy volunteers between 21 and 65 years old who are not taking medicines that can affect the metabolism of drugs in the liver and have not used St. John's wort for at least 30 days may be eligible for this 25-day study. Participants will take a 400-mg dose of Tegretol after fasting overnight. Blood samples will be drawn the next day during a 12-hour clinic stay at the following...

Drug interactions due to inductioninhibition of hepatic enzymes

The most important antiepileptic drug interactions are those mediated by changes in the P450 enzyme system. These metabolic processes can be induced or inhibited by antiepileptic drugs, and also auto-induced (induction of the drug's own metabolism). In fact carbamazepine, phenytoin, and phenobarbital are among the most potent enzyme-inducers in the pharmacopoeia. Pharmacokinetic interactions between antiepileptics (and other drugs) are therefore very common and can have a serious impact on clinical therapeutics. In recent years the characterization of the isoenzymes involved in antiepileptic drug metabolism has greatly improved our understanding of drug interactions. There are two main families of enzymes. The P450 enzyme system is involved in the phase 1 metabolism of a number of antiepileptic drugs (Table 2.4). Five of the isoenzymes (CYP3A4, CYP2C9, CYP2C19, CYP2E1 and CYP1A2) are the most important from the point of view of the anti-epileptic drugs. Phase two reactions...

Drug interactions

Zonisamide does have drug interactions that might be expected to alter dosing requirements in some situations. Adjunctive administration of enzyme-inducing antiepileptic drugs reduced the half-life of zonisamide, in one study, from 52-66 hours to less than 27 hours with phenytoin, 38 hours with carbamazepine, 38 hours with phenobarbital, and 46 hours with valproate. Lamotrigine may inhibit the metabolism of zonisamide.

Drugs And Drug Interactions

The goal of epilepsy treatment is 'no seizures, no side-effects'. Monotherapy is preferred if possible, because of greater patient compliance with medications, better quality of life, more favourable adverse effect profile, lack of drug interactions and cost issues. However, many patients with epilepsy will require more than one AED, and many patients will also be on other medications for co-morbid conditions. This means that a large proportion of people with epilepsy are at risk of drug interactions. Drug interactions may be pharmacodynamic or pharmacokinetic. The clinical significance of a drug interaction depends on the drugs involved as well as patient factors such as age and co-morbid conditions. However, drug interactions are not necessarily harmful. There are several combinations of AEDs with synergistic effects on each other, such as lamotrigine and valproate 78 , meaning that lower doses of both are required, which may reduce cost. The combination of phenytoin and valproate...

Vagus Nerve Stimulation

The advantages of VNS include a relative lack of systemic or cognitive side-effects, absence of potential drug interaction and an automatic delivery which minimizes the problem of compliance. The disadvantages include a relatively high cost, moderate efficacy, requirement for battery renewal and the palliative nature of the intervention.

Unfavourable Pharmacokinetic Interactions between Anti Epileptic Drugs

In combining AEDs, it is beneficial to avoid complex pharmacokinetic interactions which may lead to reduced efficacy and or increased toxicity. The older AEDs are notorious for their ability to produce pharmacokinetic interactions among themselves as well as with other medications via their effect on the hepatic cytochrome P450 (CYP) enzyme superfamily 47 . Phenobarbital, primidone, phenytoin and carbamazepine all induce CYP enzymes that accelerate the breakdown of CYP-metabolized AEDs as well as many commonly prescribed lipid-soluble drugs, including oral contraceptives, cytotoxics, cardiac anti-arrhythmics and warfarin. Valproate is a weak inhibitor of mono-oxygenase and conjugating enzymes, which can slow the clearance of other AEDs, such as phenytoin and lamotrigine 47 . In comparison, few of the newer AEDs interfere with CYP enzymes and they are generally less likely to affect the metabolism of other AEDs to a clinically significant extent (Table 8.4) 47 . In particular,...

New Drug Delivery Systems

Several modes of delivering AEDs directly to the brain are being investigated 61 . The theoretical advantages of such a drug delivery system include improved efficacy with higher local drug concentrations, and avoidance of systemic adverse effects and pharmacokinetic drug-drug interactions. Conantokin-G (CGX-1007), an N-methyl-D-aspartate (NMDA) receptor antagonist, is being developed as a novel AED to be delivered intrathecally via a subcutaneously implanted infusion pump to patients with epilepsy 62 . The safety of intrathecal administration of CGX-1007 was tested in animal studies, and clinical studies are under way.

Risks Of Contraceptive Failure For Women With Epilepsy

Women with epilepsy can use hormonal contraception with the expectation of effective contraception, keeping in mind some caveats regarding dosing and drug interactions. In the general population, oral contraceptive (OC) pills, when used without missing doses, are highly reliable, having an annual failure rate of 1 1 . Realistically, however, the annual failure rate is 2-7 2 . The increased failure rate of OCs in the setting of anti-epileptic drug (AED) use was reported by Coulam and Annegers in 1979 3 . They evaluated pregnancy occurrence in 82 women with epilepsy 41 were taking OCs and AEDs together (955 patient-months) compared with 41 women with epilepsy taking OCs alone (2278 patient-months). There were three OC failures in the group taking AEDs, but no OC failures in the comparison group. In the three pill-failure patients, seizures were well controlled, indicating that medication compliance was not a factor. The derived annual failure rate for OCs in women taking AEDs is about 6...

Seizures In Intensive Care Units

In patients with seizures due to metabolic derangements, correction of these abnormalities may be sufficient to prevent further seizures from occurring. In ICU patients with seizures due to other causes, short-term treatment with an anti-epileptic agent should be considered. The choice of AED, as discussed above, depends on the patient's co-morbidities and potential medication interactions. Treatment in these patients depends largely on the underlying aetiology. For example, for metabolic abnormalities, correction of the underlying disorder will be sufficient and more effective than AEDs. In particular situations, treatment with AEDs will be advisable at least for the short term, especially when the risk of seizures outweighs the risks of treatment and when there is an underlying abnormality that cannot be corrected rapidly. Detailed review of the patient's medications and potential drug interactions should be performed in order to prevent inadvertent changes in efficacy or blood...

Other Conditions Which May Benefit From Aed Treatment

There are a number of other neurological conditions in which AEDs are used. These may occur in patients with co-existing epilepsy. It may be useful in these patients to use an AED which has efficacy for both conditions to avoid polypharmacy and drug interactions. Mood disorders are much more prevalent in people with epilepsy than in the general population 108 . This may be due partly to psychosocial issues, as well as to the underlying neurobiological reasons. The most common mood disturbance is depression, occurring in approximately one-quarter of patients. Co-morbid depression may be under-diagnosed in patients with epilepsy it may influence drug compliance and quality of life. As mentioned previously, there are possible drug interactions between some of the AEDs and antidepressants. In addition, anti-depressants may lower the seizure threshold, although the seizure risk associated with the selective serotonin reuptake inhibitors is 0.4 109 . Some AEDs may themselves have...

Seizures In Transplant Patients

The frequency of seizures in human immunodeficiency virus (HIV) patients has been reported between 3 and 11 55-57 . A prospective study on HIV patients reported that 3 had new-onset seizures during the study period. The major aetiologies were drug toxicity (47 ) and intracranial lesions (35 ) 56 . The direct effects of HIV on the brain may be the single most common cause of seizures 55, 58 . Aetiologies are listed in Table 12.6. The majority of seizures were reportedly generalized 55, 56 . Seizure management in HIVpositive patients presents particular problems, especially with respect to drug-disease and drug-drug interactions 59 . HIV-seropositive patients are at higher risk of hypersensitivity reactions. For example, 14-26 of patients who received phenytoin have been reported to develop hypersensitivity reactions 55, 58 . Patients who are hospitalized with HIV may be concomitantly receiving highly active anti-retroviral therapy (HAART). Monitoring of free-phenytoin levels is...


Obviously, this is a major issue for patients who fall with their seizures. All patients receiving phenytoin should receive supplemental calcium and vitamin D, and should be screened with bone densitometry. Allergic rash may occur. Although idiosyncratic side-effects are not common, they can occur, and patients should be advised of this possibility. These include Stevens-Johnson syndrome, aplastic anaemia, hepatic failure and a lupus-like syndrome. Monitoring of blood counts, liver function tests and electrolytes are warranted for the first 6-12 months of therapy. Drug interactions are relatively common, both with other epilepsy drugs and with drugs taken for other conditions. Interactions with other AEDs are listed in Tables 1.1 and 1.2. Phenytoin is less expensive than many alternatives, which is important for patients who are paying for their own medications. Because of phenytoin's relatively long half-life, it can be administered only once or twice a day.


Phenobarbital is the 'grandfather of anti-epileptic drugs'. It has been available for over 100 years. It is effective for most seizure types and the fact that an intravenous (i.v.) formulation is available means it is often used for treatment of status epilepticus. In the modern era, it is rarely used as first-line therapy, as studies have demonstrated that it causes more dose-related side-effects, particularly sedation, than other options 14 . Also, once started it is very difficult to withdraw without causing seizure exacerbation. Abrupt withdrawal is not recommended, and even slow withdrawal can lead to problems. The initial dose is 30-50 mg, which is best administered at bedtime. Titration to optimal dose can be achieved over several weeks. Optimal effect is usually achieved at serum concentrations of 15-45 mg l. Other dose-related side-effects include irritability, difficulty concentrating, memory loss, sedation, dysarthria and ataxia. Other reported adverse reactions include...


Ethosuximide has a very narrow therapeutic indication, with use limited to patients with absence seizures 41 . In most cases, it should be used as the sole agent only in patients who experience this seizure type in isolation, a condition seen primarily in childhood 42 . Occasionally, in patients with primary generalized epilepsy with seizure types other than absence, addition of ethosuximide as an adjunctive medication may improve seizure control. Ethosuximide can be started at 500 mg day, and titrated as tolerated, with weekly increments. Serum concentrations of 40-100 mg l are usually optimal. The most common side-effects noted with ethosuximide use include nausea and abdominal discomfort, drowsiness, anorexia and headache 41 . In rare cases, behavioural changes may be seen, including psychosis. Blood dyscrasias have been reported. Drug-drug interactions are minimal.


Patients may do well at serum concentrations of 2 mg l, while others may need levels of up to 20 mg l. Common dose-related side-effects of lamotrigine include mild tremor, double vision, headache and insomnia. Rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis, can occur. Risk is increased for children under 16, and is also more common with concomitant valproate use, and in patients who have experienced rash on other AEDs 54 . Rash almost always occurs within the first 8 weeks of therapy. Other hypersensitivity reactions, although much rarer, may be seen, including lymphadenopathy, fever, hepatic or renal failure, disseminated intravascular coagulation and arthritis 55 . Discontinuation of lamotrigine is recommended in the presence of rash or other indication of hypersensitivity, and it is very important to tell patients to call immediately with such symptoms. Rapid discontinuation can prevent a more severe, potentially life-threatening reaction. In the absence of...

Rational Polytherapy

As previously discussed, drug resistance is a relative state rather than an absolute designation, and a proportion (albeit small) of such patients may still benefit from further drug manipulation. Whether AEDs can be combined 'rationally' to achieve 'synergism' has been under intense debate. With at least 15 AEDs available to treat partial seizures, 105 duotherapy combinations are possible. Such an overwhelming number of options makes 'rational' polytherapy not only of academic interest but a practical necessity. The goal is to achieve better seizure control with combinations that may produce supra-additive (synergistic) efficacy and or infra-additive toxicity, while paying attention to any potential undesirable pharmacokinetic drug-drug interactions 29 .


Simple partial, complex partial, secondary generalized tonic-clonic and myoclonic are the most common seizure types in the aged 3, 25 . Therefore, agents that are approved for use for those seizure types are the best choices as initial therapy. First-line therapy for simple partial and complex partial seizures includes carbamazepine, gabapentin, levetiracetam, lamotrigine, phenobarbital, pregabalin, phenytoin, tiagabine, topiramate, valproic acid and zonisamide. Primary agents approved for generalized tonic-clonic events include phenytoin, topiramate, levetiracetam, lamotrigine, valproic acid and zonisamide. Primary agents available for myoclonic seizures include benzodiazepines, felbamate, levetiracetam, topiramate, valproic acid and zonisamide. The choice of any of these agents is appropriate. Adverse effects and drug interactions are more important than efficacy variables in deciding which agent to utilize 24, 28, 51-53 .

Cardiac Disease

Cardiac medications, particularly the class I anti-arrhythmics (lidocaine, flecainide, propafenone), which block sodium channels, may lower the seizure threshold even at therapeutic doses. Some cardiac medications, in particular quinidine and flecainide, are also metabolized by the cytochrome P450 system and may interact with certain AEDs (see 'Drugs and drug interactions' later in this chapter).

Hepatic Disease

Seizures occur frequently after liver transplantation. Immunosuppressants are mainly metabolized by the liver, as are most AEDs. In addition, many AEDs may induce or inhibit hepatic metabolism. These factors make management of epilepsy difficult in patients with a liver transplant. Levetiracetam may be a good choice of AED in such patients because of its predominantly renal metabolism and excretion, low protein binding, lack of enzyme induction, lack of drug interactions and broad-spectrum use in different seizure types 40 .

Elderly Patients

One study found that the mean number of daily medications for elderly patients in the community was eight, with 40 prescribed more than nine medications daily 75 . Polypharmacy increases the risk of medication non-compliance, which may in turn increase the risk of seizures. In addition, polypharmacy increases the potential for drug-drug interactions. Elderly patients are more likely to have memory problems and visual impairment and these factors make medication errors more likely. Because of the narrow therapeutic index, lower tolerability and higher adverse effect rate of AEDs in older patients, it is preferable to initiate AEDs at lower doses and titrate more slowly than is necessary in younger patients.

Secondline Treatment

Than 3000 mg day and when the drug was commenced within 4 days of the onset of SE. A further case series reported that six patients, refractory to at least two prior AEDs, responded to oral levetiracetam within 96 h at doses up to 3000 mg day 108 . No significant adverse reactions were reported. Levetiracetam may also be given via nasogastric tube in comatose patients, although absorption may be variable. Levetiracetam can now also be administered intravenously and thus represents an alternative to phenytoin in the acute setting. There are few data currently available on its efficacy. The main advantages of levetiracetam in the setting of SE are ease of administration, rapid titration, easy transition to use as a maintenance anti-epileptic drug (AED) and few drug-drug interactions. Further data are clearly needed before its use can be recommended.

Developmental Pharmacokinetics

Elimination of AEDs occurs through either renal excretion of unchanged parent drug, hepatic biotransformation to metabolites (both active and inactive), or a combination of both At birth, renal blood flow, glomerular filtration rates, and tubular secretion and reabsorption are at approximately 25-30 of adult values, but increase steadily by 6 months to 50-75 of adult function Full maturation of renal function is generally reached by approximately 1 year of age As with the gastrointestinal tract, transporter proteins participate in active renal excretion of many drugs however, knowledge regarding their maturation remains scant In general, weight-normalized doses of drugs, excreted predominately unchanged by the kidneys, need to be reduced only for neonates and infants . The cytochrome P450 (CYP) and uridine diphosphate (UDP) glucuronosyltransferase (UGT) family of enzymes catalyze biotransformation of most of the older AEDs The more recently approved AEDs are also eliminated by renal,...

When is blood level measurement required

There is no doubt that the practice of monitoring plasma drug concentrations has improved the quality of epilepsy care. It has led to an appreciation of variability of drug levels, kinetic principles, drug interactions and the value of tailoring doses to individual patient needs. Feedback from blood level measurement improves a clinician's experience and clinical acumen and, as a result, effective therapy can often be chosen now on purely clinical grounds, as shown in a recent study in which there were no differences in outcome between patients randomized to have their regimens adjusted empirically and those in whom dosage was tailored based on drug concentration measurements.

Moll in routine practice Comments

Measurements useful because response is closely linked to blood level, although kinetics are linear and often dose change can be made simply on a clinical basis. Measurements useful also to monitor the effects of drug interactions and because both the parent drug and the active metabolite contribute to clinical effect Response is only partially correlated with blood level. However, measurement is useful where lamotrigine levels are affected by antiepileptic drug interactions, interactions with the contraceptive pill, and pregnancy Measurements of limited usefulness only as response is not broadly linked to blood level. However, serum level measurement useful to monitor effects of drug interactions Measurement is of only limited usefulness, as response is only partially correlated to blood level and these vary widely through the day. However, serum level measurement is useful to monitor effects of drug interactions

Epilepsy Patient and Family Guide Second Edition

Principles of drug therapy, (5) discuss anticonvulsants, (6) discuss surgical therapies, and (7) describe other epilepsy therapies. The third section is entitled Epilepsy in Children and consists of 10 chapters that discuss (1) epilepsy in infancy, (2) Epilepsy in childhood, (3) epilepsy in adolescence, (4) outgrowing epilepsy, (5) intellectual and behavioral development, (6) how to tell children and others about epilepsy, (7) how to live an active life, (8) the education of children with epilepsy, (9) mental handicaps and cerebral palsy, and (10) how children can cope with epilepsy after their parents are gone. The fourth section is entitled Epilepsy in Adults and consists of six chapters that address (1) living with epilepsy, (2) pregnancy and menopause, (3) parenting by people with epilepsy, (4) employment issues for people with epilepsy, (5) mental health in adult patients with epilepsy, and (6) epilepsy in the elderly. The fifth sections entitled Legal and Financial Issues in...

Specific Evidence for Antiepileptic Drugs in People with ID

It is accepted practice that wherever possible the prescription of treatment should be evidence based. In the pharmacological treatment of epilepsy this will include examining material concerning efficacy, i.e., seizure control, harmful effects, and potential drug interactions relevant to the patient in question. Different study designs are necessary to provide the range of information required. Randomized, controlled trials are often time-limited and provide information on short-term efficacy and the common

Clinical use in epilepsy

Gabapentin is a useful drug in the treatment of partial and secondarily generalized tonic-clonic seizures. It has an excellent pharmacological profile, and its lack of protein binding, its lack of metabolism, and its lack of drug interactions are attractive properties. It has particular value in renal or hepatic disease and in patients on complicated drug regimens. Also, it is relatively well tolerated although it does have some side-effects, particularly at higher doses, but apart from drowsiness these are usually relatively minor. Certainly, the severe behavioural or psychiatric disturbances found with other drugs do not occur with gabapentin nor do idiosyncratic or serious systemic side-effects. There are, however, disadvantages. The drug appears to have only a rather modest efficacy, and most patients with severe epilepsy derive little benefit. Furthermore, a substantial minority of patients Dose commonly affected by co-medication Dose affected by renal hepatic disease Common drug...

Treatment strategy

Medications have been separated into older and newer groups based upon their historic regulatory approval and appearance in the U S marketplace Typically, when a medication is first approved for epilepsy, it receives an on-label indication for add-on (adjunctive) therapy for partial-onset seizures in adults Then, as experience grows and other studies are done, the use of the drug may expand to other seizure types and younger age groups as deemed appropriate As a broad generalization, most practitioners who specialize in epilepsy (epileptologists) would now prefer to initiate drug therapy with one of the newer medications . Research studies and clinical experience have shown that the newer medications may not be more efficacious than the older drugs, but they do appear to be safer, better tolerated, and have fewer drug-to-drug interactions . The AED chosen for initial therapy should be one that is highly effective for a particular seizure type or epilepsy syndrome, and be safe and well...

Contraindications and Interactions Hidden Dangers

Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it's especially important to read the label...

Epilepsy training models

Another obstacle to effective teaching about epilepsy and psychopathology is the relative delay in accessing the latest information about the AEDs, their psychiatric side effects, and drug interactions with psychotropic medications. This is especially relevant in training child and adolescent psychiatrists, as children with epilepsy are usually excluded from the already limited number of psychopharma-cological trials performed in children.

Does gabapentin and lamotrigine have significantly fewer sideeffects while providing equal or better seizure control

Purpose - Excerpt New onset epilepsy in the elderly occurs in 45,00050,000 elderly patients each year. These patients are especially vulnerable to side effects from medications because of changes caused by the aging process and the fact that these patients often have many common diseases for which they are already receiving medications for so that the likelihood of drug interactions is increased. Two new drugs, gabapentin and lamotrigine, have recently been approved by the FDA as antiepileptic drugs. These drugs have demonstrated efficacy in the treatment of partial onset seizures, the most common seizures in the elderly. These new compounds also have favorable side effect profiles and infrequent drug-drug interactions and, therefore, would be expected to be well-tolerated in the elderly.

Druginduced seizures

Patients prospectively monitored for drug toxicity. As many as 15 of drug-related seizures present as status epilepticus. In a population-based survey from Richmond, Virginia, drug overdose was the reported cause in 2 of children and 3 of adults with status epilepticus. Drugs can cause seizures due to intrinsic epileptogenicity, patient idiosyncrasy, antiepileptic drug interactions, impairment of the hepatic or renal drug metabolism, drug withdrawal phenomena, and direct cerebral toxicity (especially in intentional overdosage).

Elimination halflife

Drug interactions can also have marked effects on elimination half-life. Three-quarters of a drug is eliminated within two half-lives, and approximately 93 within four half-lives. Once a steady state has been reached, at a very rough approximation, dosing a drug at intervals equivalent to one half-life will keep trough levels within 50 of peak concentrations.


Depression is perhaps the most commonly recognized comorbidity in epilepsy patients. Estimates of prevalence range from 6 to 48 depending on the scale and the population studied, with a median near 30 (Kanner and Nieto, 1999 Hermann, 2000). While depression is noted to be higher in patients with refractory epilepsy than in those whose seizures are well-controlled (Grabowza-Grzyb et al., 2006) , it is also true that depression correlates less with seizure frequency, age of onset and duration of epilepsy than with a number of psychosocial variables (Hermann, 2000 Kendler et al., 1999). Structural pathology in frontal or temporal regions is increasingly noted to be a determinant of depression in epilepsy and other populations (Sheline, 2003). The impact of this depression on quality-of-life scales in epilepsy is substantial depression has been noted in some studies to be the most closely linked variable to quality-of-life scaled scores (Meldolesi et al.) 2006). The treatment of...


The drug is not metabolized at all and is completely excreted in an unchanged form. This lack of hepatic metabolism is of course a great advantage, and there are no pharmacokinetic drug interactions. Drug interactions Gabapentin has no known pharmacokinetic drug interactions owing to its lack of protein binding and hepatic metabolism. There is potential for interaction at the renal level, but no specific effects have been reported.

Gabapentin GBP

GBP is chemically related to GABA, but its mechanism of action remains controversial. It is effective for partial and secondarily generalized seizures, but is not as effective for primary generalized seizures. GBP has minimal side effects and no significant drug interactions. These properties make it useful among patients on multiple other drugs, par

Commercial Databases

Mosby's GenRx database (also available on CD-Rom and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Information can be obtained at the following hyperlink The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink


AED, most commonly lamotrigine or levetiracetam. While insufficient data was available for these authors to conclude that these drugs are more likely to induce remission than other AEDs, it seems plausible that the availability of a broader range of AEDs accounts for the fact that these authors obtained better rates of seizure remission in their patients with previously refractory seizures than has previously been observed. A variety of new AEDs are currently in development, some of which act in new ways on old targets and others that act on entirely new targets.36 We can expect that these new drugs will further benefit patients by having improved side effect profiles, improved pharmacokinetic properties, reduced propensity for drug interactions, less teratogenic potential, an improved spectrum of activity and, most importantly, by their ability to induce seizure remission in some patients previously considered to have intractable seizures. In the future, if modifier genes can be...

Neoplastic Disorders

Because of its noninducing properties, lack of protein binding, and lack of drug-drug interaction, gabapentin has been used to treat seizures in children with systemic cancers (204, 208). Many of these same advantages exist with levetiracetam, and the development of a commercial intravenous form may make this the drug of choice in these patients.


The lack of drug interactions, and the simple pharmac-okinetics, of levetiracetam are advantages in the elderly, although detailed studies of its usefulness in this group have not been carried out. Anecdotal evidence suggests, however, that levetiracetam is useful and safe. Age-related changes in renal function can greatly affect the clearance of the drug, and doses should be reduced accordingly. An initial dose of 125 mg is recommended, with incremental steps of 125-250 mg until an initial maintenance dosage of 750-1500 mg day is reached.


The prevalence of various forms of anxiety is very high among epilepsy patients, ranging from 19 to 60 (Jones et al, 2005). The types of disorders with increased incidence in epilepsy patients include panic disorder, generalized anxiety disorder, phobias and obsessive compulsive disorders (Beyenburg et al, 2005). Not surprisingly, focal epilepsies, especially those associated with the temporal lobe, have a stronger association than other seizure types. The effects of anxiety on quality of life are substantial and separate from the effects of depression (Cramer et al, 2005) . Cognitive and behavioral therapy can be helpful. Medication treatment decisions are often complicated by concerns about drug interactions, as well as the possibility of reducing seizure threshold.