New, Safer Antiepilepsy Drugs - Brief Article - Statistical Data Included

Family Pratice News,  Feb 1, 2000  by Sharon Worcester

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ORLANDO, FLA. -- The newer antiepilepsy drugs have improved safety profiles, compared with older drugs, but adverse effects remain a concern, Dr. Cynthia L. Harden said at the annual meeting of the American Epilepsy Society.

Gabapentin is one of the safest antiepileptics, but neuropsychiatric effects such as sedation have been reported, said Dr. Harden of the department of neurology and neuroscience at Cornell University, New York.

Extreme fatigue occurs in a minority of patients. If it occurs at low doses, gabapentin must often be withdrawn, she said.

Gabapentin-related behavioral effects, including irritability, hyperactivity, and violent outbursts, have been seen in some children. These generally occur as exacerbations in children who already are at risk due to mental retardation or attention-deficit hyperactivity disorder, Dr. Harden explained.

In rare cases, neutropenia and hepatotoxicity have occurred in patients taking gabapentin, but these cases involved patients taking multiple agents, so it is difficult to place the blame on gabapentin, she noted.

One important side effect, weight gain, was not observed in preclinical trials of gabapentin. In one study more than 20% of patients gained more than 10% of body weight. "I think this may be an overestimate because the numbers were small in this study but this is something we do need to monitor for," she said.

Lamotrigine, another newer antiepileptic, has been associated with insomnia. Patients may not associate this with the drug, so it is important to ask about it at office visits. Behavioral changes, like those seen with gabapentin, also can occur, Dr. Harden said.

Rash is another potential problem with lamotrigine. The literature shows that most rashes occur at a median duration of treatment of 6 weeks and at a median dosage of 175 mg/day. Rashes that require taking the patient off the drug generally occur in the first 3 weeks, however.

Rashes are seen more often in children than adults. Stevens-Johnson syndrome occurs about four times more often in children than in adults, she noted.

Rare side effects of lamotrigine--Dr. Harden found only one clear-cut case of each of these in the literature--include neutropenia and thrombocytopenia.

A more controversial drug in terms of its neurocognitive and neuropsychiatric effects is topiramate, which has been associated with encephalopathy as well as with cognitive dysfunction, she said.

These effects occur most often when the starting dose of topiramate is too high and when the dose is escalated too quickly. Starting slowly and at a low dose will help avoid encephalopathy as well as much of the cognitive dysfunction. Still, patients on this drug need to be followed closely to check for problems with verbal function and mood effects.

"I have patients who I'm able to maintain at doses lower than the maximum of 400 mg, and they feel fairly well," Dr. Harden commented.

Renal calculi and weight loss are potential problems in patients on topiramate; each has been seen in 1.5% of patients. A few patients have had weight loss severe enough to lead them to stop treatment.

Tiagabine, like many of the other antiepileptics, is infrequently associated with cognitive and neuropsychiatric effects such as impaired concentration, fatigue, confusion, anxiety, and nervousness. In very rare cases, tiagabine is associated with alterations in hematologic and hepatic parameters, Dr. Harden said.

Another rare effect of tiagabine is the idiosyncratic appearance of spike/wave discharges on electroencephalography. The risk of this is unclear, but the literature shows that it occurs at a minimum dosage of 30 mg/day and most cases occur at higher dosages. The patients reported in the literature responded to dosage reductions and benzodiazepine treatment, Dr. Harden said.

Always Check Blood Levels In Patients on Old or New Antiepilepsy Drugs

ORLANDO, FLA. -- Monitoring therapeutic blood levels in patients on antiepilepsy drugs is important, even in patients taking newer drugs, Charles E. Pippenger, Ph.D., said at the annual meeting of the American Epilepsy Society.

It is "nonsense" to worry that such monitoring gives patients the impression that the medications are unsafe. In fact, monitoring can improve the patient's quality of life, he said.

"If you're only monitoring when you think somebody might be toxic, you are doing your patient a great disservice and you are doing yourself a great disservice," said Dr. Pippenger of Grand Valley State University Allendale, Mich.

There are several other instances when monitoring is of great value, including when the desired therapeutic goal is reached, when noncompliance is suspected, when breakthrough seizures occur, when drug-drug interactions are a concern, when side effects occur, and when other drugs are added or removed.

When a therapeutic goal is reached it's important to determine the blood level so it can be maintained. When side effects occur, it's important to know what level to avoid. When breakthrough seizures occur, monitoring helps determine if a toxic drug reaction is taking place or if the patient has been noncompliant, he noted.