Anti-epileptic drugs (AEDs) are the main means of controlling epileptic seizures, and about 65% to 85% of epilepsy patients have seizures that can be controlled by AEDs.
However, the inconvenience caused by daily medication to patients’ work, life and study, the adverse effects of medication on patients’ cognition and psychology, the fear of drug teratogenicity in women of childbearing age during pregnancy, and epilepsy has been a long-standing problem. Seizures and other reasons prompt epilepsy patients to try to withdraw the drug, and at the same time, relapse after drug withdrawal has become a problem that doctors and patients have to worry about.
This article focuses on the factors that affect the prognosis of drug withdrawal in epilepsy patients and the choice of withdrawal timing, hoping to improve the understanding of epilepsy patients on drug withdrawal and guide clinical practice.
Risk factors for seizure recurrence after withdrawal
01.Age of onset
A U-shaped relationship between seizure age and seizure recurrence after drug withdrawal, with increased risk at birth, nadir at 3 to 4 years of age, increased again at 10 years of age, and 25 tends to stabilize with age. Epilepsy occurring in adolescence has a significantly higher risk of relapse after drug withdrawal than epilepsy occurring in childhood and adulthood.
02.Causes of epilepsy
Structural lesions are a high risk factor for seizure recurrence after drug withdrawal. Compared with hereditary or unexplained epilepsy, patients with epilepsy of structural etiology have a significantly higher risk of drug withdrawal and relapse;
Congenital malformations of the brain, previous neurological damage, brain tumors, congenital metabolic disorders, trauma, stroke, syphilis, AIDS, perinatal injury and developmental delay are all high risk of recurrence after drug withdrawal factor.
03.Type of seizure
Patients with different subtypes of generalized seizures have different risks of recurrence after drug withdrawal. Both generalized tonic-clonic and myoclonic seizures lead to a high risk of recurrence after drug withdrawal, while absence The risk of recurrence of an episode is usually low.
The effect of different epilepsy syndromes on the risk of relapse after drug withdrawal mainly depends on their treatment effect and long-term prognosis.
Childhood epilepsy syndromes such as childhood absence epilepsy, benign epilepsy with centrotemporal spikes, etc. belong to benign epilepsy with good prognosis. The epilepsy remission state can be maintained for a long time after drug withdrawal, and there is a risk of recurrence. low;
The juvenile myoclonic epilepsy, Lennox-Gastaut syndrome, West syndrome and other epilepsy syndromes are more likely to develop into refractory epilepsy, and the long-term prognosis is poor. Epilepsy is very likely to occur after the drug.
05.Effects of AEDs
Good epileptic remission status reduces the risk of relapse after drug withdrawal, and longer duration of epilepsy remission reduces the risk of epilepsy relapse after drug withdrawal.
Achieving at least 6 months of seizure freedom immediately after initiation of initial AEDs suggests a higher rate of long-term epilepsy remission in patients. A rapid response to treatment within 3 months was a significant predictor of seizure freedom for at least 5 years.
Patients treated with more than 1 AED have a significantly higher risk of relapse after drug withdrawal than patients treated with monotherapy; patients with epilepsy uncontrolled with 2 or more AEDs Withdrawal should not be considered after a state of epileptic remission has been achieved.
Whether EEG can predict the risk of recurrence after drug withdrawal The current research results are not completely consistent. The changes of EEG before and after drug withdrawal may have a certain predictive value for the risk of recurrence after drug withdrawal. .
Patients with multi-regional paroxysmal abnormalities or epileptiform discharges on EEG before drug withdrawal are at higher risk of recurrence after drug withdrawal; EEG coexistence of slow wave and spike discharges was also associated with a higher risk of recurrence after AEDs withdrawal.
Clinically, some patients who do not follow the doctor’s advice to withdraw AEDs after seizure control usually have a significantly higher risk of relapse after withdrawal than the epilepsy patients who follow the doctor’s advice.
In addition, seizure duration and number of seizures were not shown to be clear risk factors for recurrence after drug withdrawal.
Individualized withdrawal timing
Patients with epilepsy who no longer experience seizures while taking AEDs may consider stopping the medication. At present, the appropriate timing of withdrawal of AEDs in the setting of epilepsy remission remains controversial.
The results of most studies show that tapering and discontinuation should generally be considered in epilepsy patients who have been seizure-free for at least 2 years or more, depending on the type of epilepsy, duration of remission, and type of AEDs .
1) Studies have shown that drug withdrawal does not increase the risk of epilepsy recurrence in patients with focal epilepsy when the duration of epilepsy remission is greater than 5 years. In patients with focal epilepsy, drug withdrawal can be attempted after seizure control for more than 5 years.
2) Patients with secondary epilepsy such as AIDS, syphilis, and viral encephalitis need to take AEDs for a long time. A withdrawal attempt is recommended.
3) For patients with idiopathic generalized epilepsy, the currently accepted solution is to combine EEG results in the absence of seizures for 2 to 4 years Attempt to start withdrawal.
4) Patients with benign childhood epilepsy syndromes such as childhood absence epilepsy, benign epilepsy with centrotemporal spikes, and benign childhood epilepsy with occipital spikes usually have seizures Withdrawal can be started 1 to 2 years after control.
5) For epilepsy patients with poor early response to AEDs, the seizure-free period before drug withdrawal should be extended.
6) For epilepsy patients phenobarbital and benzodiazepine AEDs, withdrawal speed is required Slower. Dose adjustment of only one drug at a time is recommended for patients treated with more than one AED.
7) The decision to withdraw medication for epilepsy patients also needs to consider the patient’s social attributes and needs. Patients with epilepsy and those with frequent driving or high-risk jobs should have different withdrawal decisions.
The 2 years after drug withdrawal is a high-risk period for relapse. Once drug withdrawal starts, the drug dose should be reduced steadily and slowly during the above-mentioned period, and patients should be paid attention to their social and psychological conditions and be advised to stay away from the drug. Factors associated with epilepsy recurrence.
How best to withdraw AEDs has not yet been established, and it is reasonable to reduce the dose slowly to minimize the potential risk of withdrawal recurrence.
When a patient experiences a recurrence of epilepsy during drug withdrawal, it is recommended to restart AEDs treatment immediately and intensify or adjust the existing AEDs treatment plan according to the treatment situation.
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 Xu Shoucheng, Liang Xue, Gan Caiting, et al. Prognosis and influencing factors of patients with recurrent epilepsy after drug withdrawal [J]. Chinese Journal of Neurology, 2021, 54(03 ):211-218.
 Ou Shuchun, Xia Lu, Li Rong, et al. Long-term outcomes and risk factors for recurrence after withdrawal of epilepsy in seizure-free patients [J]. Stroke and Neurological Disorders, 2019( 1):82-86.
 Wang Xiaoshan, Sun Jintao, Shi Qi. On the understanding of drug withdrawal in epilepsy patients [J]. Chinese Journal of Neurology, 2021,54(01):75-78.< /p>