Antiseizure Drugs

Antiseizure medications, also known as anticonvul-sants and antiepileptics, treat seizure disorders by decreasing abnormally high levels of brain activity. Various types of seizures exist. The most easily recognized are tonic-clonic seizures, also known as grand mal seizures, with significant muscle activity, loss of consciousness, and often loss of bowel and bladder control. A second type of seizure is absence seizures, which lead to temporary, sometimes brief losses of consciousness and postural tone. Myoclonic seizures are characterized by muscle jerks. These three types are known as generalized seizures because of their widespread effect in the brain. The other category of seizures is called partial, because they involve only one portion of the brain. Partial seizures are further divided into either complex, if they cause loss of consciousness, or simple, if they do not. Temporal lobe seizures, which are commonly complex partial seizures, include a variety of psychological and sensory symptoms such as feelings of unreality and smelling burning rubber. Status epilepticus is a state of continual or closely spaced seizures that can lead to brain damage and death. All of these conditions can be effectively treated with antiseizure medications.

The majority of antiseizure medications are believed to work through one of two mechanisms. One mechanism (for medications like carbamazepine, phenytoin, lamotrigine, oxcarbazepine, valproic acid, and topiramate) is through blocking the channels that regulate sodium flow in brain neurons, and the other mechanism (for phenobarbital, tiagabine, valproic acid, gabapentin, topiramate, and clonazepam) increases the activity of gamma-aminobutyric acid (GABA) neurons in the brain. GABA is the main inhibitory chemical transmitter in the brain, and increasing GABA receptor activity decreases the amount of brain electrical activity and raises the threshold for an epileptic seizure. Other antiseizure drugs decrease calcium channel flow (valproic acid and ethosuximide) or block glutamate transmission (topiramate). These diverse actions all effectively decrease abnormal levels of activation in brain neurons.

Although the drugs in this class were designed to treat seizure disorders, they are also useful in treating other disorders. For patients with bipolar disorder, for example, antiseizure medications have become first-line treatment. Valproic acid, carbamazepine, and lamotrigine are effective treatment of manic episodes. Valproic acid is also effective as a maintenance medication for bipolar disorder and may be a particularly effective treatment for the rapid cycling subtype of bipolar disorder, characterized by four or more mood phases in 1 year. Other clinical uses for antiseizure medications include carbamazepine for trigeminal neuralgia, gabapentin for postherpetic neuralgia (as well as other neurological pain), and phenytoin for migraine headaches. Clonazepam is a benzodi-azepine, and its sedating effect led to its use as an adjunct in the treatment of anxiety disorders, such as panic disorder and as a sleep aid.

Valproic acid and carbamazepine have ranges for therapeutic blood levels. Therapeutic use (for seizure disorders or bipolar disorder) requires titration to these ranges. After therapeutic levels are achieved, routine monitoring follows blood levels on a regular basis.

Most antiseizure drugs have low abuse potential because they do not generate euphoric or other reinforcing effects. Significant exceptions are phenobarbital (a barbiturate) and clonazepam, which have sedating and reinforcing effects that can lead to abuse and dependence. In addition, there have been case reports describing gabapentin abuse and withdrawal in patients with preexisting cocaine or alcohol abuse.

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