Treatment for epilepsy includes medication, ketogenic diet, vagus nerve stimulation, and surgery, with medication being the primary treatment. 70%-80% of newly diagnosed epilepsy patients can have their seizures controlled by taking single antiepileptic drugs (AEDs). Surgery and r-knife therapy are mainly used for refractory epilepsy in which drug therapy has failed and there is an accurate localization of the lesion. Long-term regular treatment is one of the basic principles of epilepsy drug therapy, but many patients with epilepsy have poor compliance, stopping, reducing, or changing their medications without authorization, and believing in surgical treatments that can “fix” epilepsy once and for all, resulting in poor control of epilepsy and a heavy burden on the patient’s family and society. The need for long-term standardized management of epilepsy medication is urgent.
The goals of long-term epilepsy management are:
(1) To establish a good doctor-patient relationship, improve patient compliance, and promote standardized treatment to enable long-term seizure control;
(2) To minimize or avoid adverse drug reactions during the treatment process and to improve the retention rate of patients;
(3) Treatment of related co-morbidities;
(4) Improving patients’ quality of life, maintaining psychological well-being, and enabling their social reintegration.
Operational procedures for the long-term management of adult patients with epilepsy.
Step 1: Diagnosis of epilepsy.
History is the key to the diagnosis of epilepsy, and details of the seizure process and past and family history should be understood in detail. EEG examination (especially recorded during seizures) is important for diagnosis, and long-range video EEG is of great value in confirming and typing epilepsy. After confirming epilepsy, the type of seizure or syndrome is identified and the cause of epilepsy is sought.
Step 2: Administer medication.
Indications for medication: Most patients should choose appropriate medication after a clear diagnosis. For first seizures or those with <1 seizure/year, the patient and family should be informed of the risks and benefits of AEDs and decide whether to administer medication. Medication should be initiated in first-episode patients with the following conditions: neurological deficits, definite epileptiform discharges on EEG, structural brain abnormalities on imaging, and patients or family members who find it difficult to accept the risk of having another seizure.
Drug selection: The choice of medication for initial treatment is critical, and the long-term prognosis of most patients with epilepsy is related to the availability of regular antiepileptic therapy in the early stages of onset. Drug selection based on seizure type and syndrome classification is a basic principle of epilepsy treatment. Proper judgment of seizure type and epilepsy syndrome is a prerequisite for the selection of AEDs; improper drug selection not only makes treatment ineffective, but may also aggravate seizures. Drug selection also requires consideration of combined medications, co-morbidities and physiological characteristics and life needs of patients with epilepsy of different ages, side effects, drug sources and costs, etc. Long-term efficacy and tolerability should be taken into account to improve treatment retention.
Step 3: Long-term management and treatment of epilepsy.
Involve the patients themselves and their families in the decision making of treatment, fully consider the patient’s requirements, and develop a long-term good treatment follow-up plan; first, advocate a standardized and individualized antiepileptic treatment plan to effectively control seizures; second, pharmacological treatment should be accompanied by somatic and psychological rehabilitation, including knowledge learning, vocational skills training, and guidance on employment and marriage, so that patients can return to school and society. In addition, treatment of co-morbidities (depression, anxiety, other systemic disorders, etc.) should be actively completed. By implementing the above three levels of long term management, the goal is to control seizures while improving the patient’s quality of life as much as possible.
Discontinuation, medication changes and combination of medications.
Most patients do not require lifelong medication. Discontinuation may be considered after 3-5 years of complete control of generalized tonic-clonic seizures and 1-2 years after cessation of atonic seizures, but there should be a slow dose reduction process of not less than 1-1.5 years. Complex partial seizures may require long-term medication. If there are still epileptiform discharges on EEG, it is better to withhold the drug reduction. Abrupt discontinuation of medication is absolutely prohibited to avoid the occurrence of persistent status epilepticus.
The basic principle of antiepileptic drug therapy is to use a single drug whenever possible. If treatment is ineffective, another single drug may be switched, but there should be a transition period during the switch. In patients where monotherapy is ineffective, a combination of drugs may be considered.
The combination of drugs should be noted as follows.
(1) Try to avoid combining drugs with the same pharmacological effect;
(2) Try to avoid the combination of drugs with the same adverse effects;
(3) Do not use multiple drugs in combination as broad-spectrum antiepileptic drugs;
(4) Combination of more than 3 drugs is generally not recommended.
Long-term management of women with epilepsy.
Women with epilepsy face menstrual and endocrine problems and fertility challenges. The possible effects of long-course treatment with AEDs should be fully considered when starting a treatment regimen for women with epilepsy, and drugs that interfere with the hypothalamic-pituitary-ovarian axis (e.g., phenytoin sodium, phenobarbital, valproic acid, carbamazepine) should be avoided as much as possible.
Menstrual epilepsy.
The relationship between seizures and the menstrual cycle should first be determined by temporarily increasing the dose of AEDs for the first 2-3 days of the month when seizures are likely to worsen, until 2 days after the seizure condition has resolved and then tapering to a maintenance dose, or adding clonidine during this period. Progesterone may also be used as add-on therapy for menstrual epilepsy, but needs to be evaluated by an endocrinologist or gynecologist; higher doses of progesterone may affect the metabolism of AEDs by liver enzymes.
Planned epilepsy:
For women with epilepsy who are effectively controlled and likely to taper off medication, expectant motherhood is recommended 6 months after discontinuation of AEDs. If discontinuation of AEDs is not possible and pregnancy is planned, the patient should be advised to adjust the AEDs to as low a dose as possible for monotherapy before pregnancy and to advise that both the seizures themselves and the AEDs have a negative impact on the fetus.
During pregnancy and the perinatal period:
Women with epilepsy should be followed and monitored in close collaboration with the obstetrician. The primary goal of management is to minimize the impact of seizures and AEDs on the fetus during pregnancy. Pregnant women with epilepsy are advised to adjust their medication every 3 months based on AEDs blood level monitoring. Avoid polypharmacy as much as possible when seizures can be controlled. The lowest possible drug dose in patients on monotherapy. valproate and phenobarbital have the highest teratogenic rates among AEDs, and recent studies have shown a dose-dependent relationship between fetal exposure to valproate and cognitive decline, which should be avoided whenever possible. A variety of factors, including pain and stress, can increase the risk of seizures during labor and delivery, and patients are advised to deliver at a hospital where they are available. Pregnant women with epilepsy taking enzyme-induced AEDs (e.g., carbamazepine, phenytoin sodium, phenobarbital) are prone to neonatal vitamin K deficiency during delivery and require supplementation to prevent neonatal hemorrhage. The dose of AEDs needs to be adjusted promptly after delivery, especially in patients with higher doses of medication.
Diagnosis of elderly patients with epilepsy.
Long-term management of geriatric epilepsy needs to begin with diagnosis. The elderly often have difficulty providing an accurate history due to memory impairment, difficulty expressing themselves, and living alone, so it is important to be patient in taking a history. There are many underlying pathologies in the elderly, and the diagnosis of epilepsy should be differentiated from hypoglycemia, TIA, transient global amnesia, and cardiogenic seizures, and related tests need to be selected to exclude non-epileptic diseases. The most common cause of geriatric epilepsy is cerebrovascular disease. Metabolic abnormalities (hypoglycemia, hyperglycemia, hyponatremia, uremia, hypocalcemia, etc.) and drugs (theophyllines, antipsychotics, antibiotics, levodopa and thiazide diuretics, etc.) are also common causes of seizures in the elderly. Elderly patients with epilepsy should be actively sought out for the cause and treated accordingly.
Selection of drugs for the treatment of geriatric epilepsy.
The specific physiology of the elderly patient determines the complexity of the selection of AEDs and the management of co-morbidities. AEDs are recommended if the elderly patient has more than 1 seizure without a clear cause, and also as early as possible after the first seizure if there is a clear epileptiform discharge on EEG and/or clear structural damage on imaging. It is also necessary to take into account the treatment of co-morbidities (diabetes, hypertension, osteoporosis, etc.) and to avoid choosing drugs that aggravate co-morbidities. Epilepsy in the elderly is mostly symptomatic, with partial seizures accounting for the majority of cases. The International League Against Epilepsy (ILAE) guidelines recommend lamotrigine and gabapentin as initial treatment for partial-onset seizures in elderly patients with epilepsy.
AEDs in elderly patients with epilepsy with hepatic and renal insufficiency:
The starting dose and target dose of AEDs should be reduced accordingly in elderly patients due to decreased hepatic and renal function, and the rate of drug dosing should be slowed down, and blood concentration monitoring should be strengthened. When liver function is abnormal, drugs with less impact on liver function such as lamotrigine, topiramate and levetiracetam can be used. When the glomerular filtration rate decreases, the dose of water-soluble drugs such as gabapentin should be reduced. For elderly patients with partial-onset epilepsy with renal insufficiency, the preferred drugs are lamotrigine and levetiracetam.