In most cases, initial antiepileptic drug (AED) therapy is selected from a relatively short list of AEDs determined primarily by the suspected epilepsy syndrome, as previously described in Chapter 71. However, there are numerous alternative AEDs, and in many cases it is useful to consider individual patient features, such as demographics, medical comorbidities, and concomitant medications, when choosing therapy.
Many antiepileptic medications carry a risk of birth defects in pregnancy, but in most cases uncontrolled seizures carry a greater risk to the child. The teratogenic risk varies by drug, with lamotrigine felt to be the lowest risk and valproic acid the highest. When planning for a future pregnancy, transitioning to a lower-risk drug should be considered, and transition away from valproic acid in particular is usually advised. Caution should be exercised in switching drugs once pregnancy has occurred, however, due to the risk of breakthrough seizures.
Untreated patients with frequent tonic-clonic or disabling seizures require rapid treatment and are not good candidates for medications that require a long period of uptitration, most notably lamotrigine, but also topiramate and zonisamide.
Patients of Asian, South-Asian, and Indian descent who carry the HLA-B*15:02 genotype are at higher risk of Stevens-Johnson syndrome with carbamazepine, oxcarbazepine, and phenytoin. These medications should be avoided if genotype testing is positive or unknown.
There is evidence for a synergistic effect between valproic acid and lamotrigine in the syndrome of juvenile myoclonic epilepsy. Slow titration and frequent monitoring are recommended, as valproic acid will raise the serum level of lamotrigine.
Gabapentin, pregabalin, carbamazepine, and oxcarbazepine can be used to treat neuropathic pain. Topiramate, zonisamide, and valproic acid can be used to treat migraine. Lamotrigine may help with neuropathic pain, and for some patients may help with migraine, but a common side effect of lamotrigine is headache.
Lamotrigine, oxcarbazepine, valproic acid, and carbamazepine have varying degrees of mood-stabilizing effects. Levetiracetam can cause significant irritability, which may be improved with treatment with pyridoxine. Perampanel is also associated with significant adverse neuropsychiatric effects.
Elderly patients are at higher risk of side effects, particularly those related to cognition and balance. Medications are often started at lower doses in elderly patients. For elderly patients with no other significant medical comorbidity, lamotrigine, and levetiracetam are commonly used first-line agents. Lacosamide, zonisamide, and gabapentin are also considered well tolerated in this population.
Most medications may be used in patients with hepatic disease, although many require dosage adjustment and some agents are potentially hepatotoxic. In patients with mild renal disease, many agents can be used with appropriate dosage adjustment. Patients on hemodialysis often require more complex drug regimens with additional doses given immediately after dialysis.
In a patient on oral contraceptives, warfarin, or with a malignancy requiring chemotherapy or a chronic infection requiring long-term antimicrobials (e.g., human immunodeficiency virus, hepatitis B virus, or hepatitis C virus), consider the impact of drug interactions. These interactions may make contraception, chemotherapy, or antimicrobial therapy ineffective, or lead to subtherapeutic or dangerously supratherapeutic anticoagulant levels in the case of warfarin.