Lamotrigine (la mo tri jeen; Lamictal - Burroughs Wellcome), a phenyltriazine derivative, has been approved by the US Food and Drug Administration for use in addition to other antiepileptic drugs in adults with partial seizures. Since this diagnostic category includes the largest number of patients with intractable epilepsy, new drugs with antiepileptic activity are usually tried first for this indication. Lamotrigine was first marketed abroad in 1990 and is now available in more than 50 other countries.

The FDA has warned that the antiepileptic and mood-stabilizing drug lamotrigine (Lamictal, and generics) can rarely cause hemophagocytic lymphohistiocytosis (HLH), a serious and potentially fatal immune-related reaction.1HLH, which can be familial, occurs most often in infants, but can occur at any age. Often induced by Epstein-Barr Virus infection (HIV infection and non-Hodgkin's lymphoma are other common triggers), HLH is characterized by an unremitting activation of CD8+ T cells and macrophages.2 If untreated, it causes organ damage, particularly in the liver, bone marrow, and CNS; organ...

Tiagaine (Gabitril - Abbot), a gamma-aminobutyric acid (GABA) uptake inhibitor, has been approved by the FDA for oral use as an adjunct to other drugs for treatment of partial seizures in patients more than 12 years old. Since most adult patients with resistant epilepsy have partial seizures, new antiepileptic drugs are usually tried first for this indictation.

Bipolar disorder is characterized by episodes of mania, hypomania, and depression. Recurrences of manic or (more frequently) depressive symptoms are common. About 15-20% of patients with bipolar disorder die by suicide.

When used for the appropriate seizure type, antiseizure medications (ASMs) are roughly equivalent in efficacy. In addition to the seizure type, the choice of drug is usually based on factors such as ease of use, spectrum of activity, adverse effects, interactions with other drugs, presence of comorbid conditions, suitability for elderly persons and those with childbearing potential, and cost. Treatment should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures persist, expert clinicians generally...

Anticonvulsants are now widely used for treatment of psychiatric illnesses, particularly bipolar disorder. Lithium is the standard drug for treatment of bipolar disorder, but it can cause severe toxicity, serum concentrations must be monitored, and it is not effective in some patients.

Topiramate (Topamax - Ortho-McNeil) has been approved by the US Food and Drug Administration (FDA) for oral use as an adjunct to other drugs in adult patients with partial seizures. Since this diagnostic category includes the largest number of patients with refractory epilepsy, new drugs with antiepileptic activity are usually tried first for this indication. Topiramate (toe pyre' a mate) is a structurally unique agent chemically related to the D-enantiomer of fructose.

Rufinamide (Banzel - Eisai), a triazole derivative structurally unrelated to other marketed antiepileptic drugs (AEDs), has been approved by the FDA for treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥4 years old.

Zonisamide (Zonegran - Elan Pharma), a sulfonamide chemically unrelated to other antiepileptic drugs, has been approved by the FDA for adjunctive use in adults with partial seizures. Zonisamide has been available in Japan for more than 10 years.

The equivalence of generic drugs to their brand-name precursors continues to be controversial. The last Medical Letter review of this subject (2002) concluded that well-documented therapeutic inequivalence between brand-name and FDA-approved generic drugs had not been reported. Is that still true? New data have become available for some drugs.