Drug-induced seizures: prevalence, risk factors, treatment and prevention

Abstract

There is a growing interest to the problem of drug-induced epileptic seizures (ES) due to their relatively high prevalence, poor prognosis, a large number of different drugs associated with the development of drug-induced ES, and low awareness among general practitioners. Drug-induced ES are most often associated with the use of antidepressants, antipsychotics, antiepileptic drugs (overdose or as a result of discontinuation), antibiotics, immunosuppressants and immunomodulators, antitumor agents, analgesics, central nervous system stimulators, anesthetics etc. The prevalence of drug-induced ES varies with different drugs. It is estimated that about 6.1% of the first occurring ES are drug-induced. Risk factors for drug-induced ES include a history of epilepsy or ES, cancer, blood-brain barrier dysfunction, several concomitant neurological diseases, mental disorders, childhood, old and very old age, fever, impaired liver metabolism in patients with liver diseases, impaired drug excretion in patients with kidney diseases, polypharmacy, pharmacokinetic properties of the drugs themselves, allowing them to penetrate the blood-brain barrier in the central nervous system (lipophilicity, transport and communication with blood plasma proteins), drug concentration in blood serum, method and frequency of drug administration, single and daily doses of drugs. No clinical guidelines for the management of patients with drug-induced ES are available. It is recommended to identify patients at risk: elderly patients, patients with impaired liver and kidney function and patients receiving drugs that can cause ES and/or lower the seizure threshold. Benzodiazepines are the first-line treatment in drug-induced status epilepticus, barbiturates and propofol are the second-line treatment. The general principles for the prevention of drug-induced ES include careful selection of the optimal dose of drugs that can cause ES, especially in patients with impaired liver and/or kidney function, monitoring of several parameters in blood serum (for example, liver enzymes, electrolytes, glucose etc.), monitoring of the blood plasma concentration of certain drugs, avoiding the simultaneous administration of several drugs that stimulate the central nervous system, and a rapid discontinuation of such drugs.