Seizures and Epilepsy (Question 11)
11. What are the Anti-Epileptic Medications?
Development of anti-epileptic medications was “very slow” until 1997, when the first new anti-epileptic drug was introduced. Prior to this, the traditional anti-epileptic medications were the only option.
Traditional anti-epileptic medications
Good for generalized and partial seizures, and may be used for febrile seizures. Recently, more frequently used in the neonatal period and rarely used after 5 years of age because of its potential to cause learning difficulties. Side effects include hyperactivity and other behavioral difficulties in about half of the children treated (ages 2-10). Drowsiness, rashes, and learning difficulties may also occur. Rare impairments of liver functions and blood counts were reported as well. Phenobarbital is best tolerated in children less than 1 year of age.
Same as Phenobarbital. Metabolizes to Phenobarbital plus PEMA. It causes more sedation than Phenobarbital and may be helpful in some seizures poorly controlled with Phenobarbital.
Most effective in partial seizures, but also good for generalized seizures and status epilepticus. Dilantin is an excellent medication for and emergency situation, such as status epilepticus (a prolonged seizure lasting more than 20 minutes. It is also helpful for the control of seizures that occur on an intermittent basis. The problem with phenitoin, however, is that it is plagued by many side effects including hypertrophy (swelling) of the gums, coursing of facial features, hair growth on facial areas, and brain atrophy over a long period of use. It may also cause the regular side effects, including allergic reaction, and blood count and liver enzyme dysfunction. The allergic reaction may be severe (Steven Johnson’s) and life threatening.
Tegretol in its various forms is an excellent medication. It is mostly used for partial seizures. Myoclonic seizures and atypical absence seizure may worsen significantly due to Tegretol. In general it is very well tolerated, has some transient sedation, usually resolving in 3 days. Tegratol may also cause life threatening blood count and liver dysfunction. It may also cause a severe rash of Steven Johnson’s typed and other allergic rashes.
Valproic acid (Depakene)
Valproic acid is an excellent anti-convulsant for generalized, as well as focal seizures. Recently it has started to gain use for non-convulsive disorders including migraine prevention and as a mood stabilizer for manic-depressive disorders.
Valproic acid comes in depakene and depakote forms. The depakote is better tolerated with regards to abdominal pain syndromes due to an enteric coating protection.
Seizures controlled with this medication include myoclonic seizures, absence seizures, and mixed type seizures. Side effects of valponic acid include initial transient sedational and abdominal pain (better tolerated with the depakote form). It may also increase the appetite, causing weight gain, cause some transient hair loss that improves with zinc supplementation, and rarely cause liver and blood count abnormalities. Hyperammonemia and pancreatic dysfunction were reported as well. In young children younger than 3, and especially younger than 2, valponic acid may cause a severe fatal liver disease in a frequency as high as 1 per 300.
Many patients taking valponic acid may have an associated carnitine deficiency. Carnitine can be supplemented with carnitor syrup or tablets.
Good for absence seizures only. Zarowtin is one of the safest anti-convulsant available. Hematological side effectsand allergic reactions were reported. Drowsiness, headaches, and abdominal pains may occur as well.
Klonopin is a benzodiazepine (valium like medication). It may be helpful for myoclonic generalized and partial seizures. It may help for infantile spasms or Lenox-Gastaut syndrome. Side effects are mostly related to sedation, drooling, cognitive impairment, and hyperactivity.
The new anti-epileptic medications
Since the early 1990’s, 9 new anti-epileptic medications were introduced to the market. These are, for the most part, medications designed to work on a specific seizure control mechanism and, therefore, at times more safe and effective than the old anti-convulsants.
A very effective anti-convulsant, even for severe and resistant seizures, such as Lenox-Gastaut syndrome, generalized absence, myoclonic and focal seizures.
Now its use is limited to extremely rare instances due to severe fatal blood and liver damage associated with this medication.
Trilepital is an excellent and very safe anti-convulsant. It is very similar to caramazepine (Tegretol) in structure, but designed to have the epoxide moiety. The epoxide is the part of carbamazepine responsible for the drowsiness, the severe allergic reactions and the very concerning liver damage and blood dyscrasia that may cause fatal side effects. The seizure control abstained with Trilepital is as good and in some situations better than with Tegretol. Side effects are minor, may cause some temporary drowsiness, mild allergic reaction, and decreased sodium level in the elderly. In short, Trilepital is an improved Tegretol, more effective, better tolerated and that has never been the cause of any fatal side effects.
Another excellent anti-epileptic medication with multiple mechanisms of action. Good for focal and generalized seizures, was found helpful with Lenox-Gastaut syndrome, infantile spasm, and other seizure types. Generally it is very well tolerated. It may cause a decrease in the appetite and psychosis. At times it may also be associated with a temporary sedative effect. For some children it may be the only medication to be able to completely control frequent intractable seizures.
This is another anti-convulsant medication with a design in mind. Gabapentin was an attempt to mimic the GABA molecule. GABA is an inhibitory neurotransmitter; theoretically increasing GABA concentration would decrease the brain excitation and stop seizures. Taking GABA itself (available in health food stores) would be useless, since GABA doesn’t cross the blood-brain barrier; Neurontin was designed to have a GABA structure yet be able to penetrate into the brain. It is a very safe anti-convulsant, but its efficacy is questionable. To achieve good seizure control, one has to treat patients with very high doses of Neurontin. The side effects include mostly some dizziness and drowsiness.
Other uses were found for Neurontin, including the treatment of migraines (as a preventative agent), neuropathies, and trigeminal neuralgia. The actual mechanism of action of this medication is unknown, but it clearly isn’t what it was designed to be.
Its main indication is as an adjunct therapy for partial seizures.
Good for generalized and partial seizures, may be effective for absence seizures, atomic seizures, and Lenox-Gastaut syndrome.
It is an effective well tolerated medication that may be associated with the development of a severe rash, especially if combined with valproic acid. Recent studies, however, indicate that the rash doesn’t occur frequently if the dose is very gradually titrated upwards. Other side effects are mild and consist mostly of some dizziness, drowsiness, or headaches.
Unavailable in the United States due to some irreversible changes in visual fields reported in association with its use. Still a very important anti-epileptic medication due to its beneficial effect in infantile spasms. It was shown to stop these severe seizures in 3 out of 4 children who have touberous sclerosis and infantile spasms. It is associated with much less adverse reaction compared to ACTH (the standard treatment for infantile spasms).
Incidentally, of my patients, the ones who were treated with Sabril for the infantile spasms had the best long-term outcome. All of them currently seizure-free, off any other anti-convulsants, and followed by me for some mild AD/HD and behavioral difficulties or some mild speech delay.
Sabril is another one of the GABA designer drugs and the only designer drug that is actually and effectively doing what it was designed to do. Sabril blocks the degradation of GABA, by blocking the effect of the enzyme GABA transamiase, thus increasing GABA concentration in the presynaptic area.
Other side effects of Sabril, other than the visual field abnormalities include rare psychosis and some other mild fatigue or gastrointestinal upset, which are related.
This is the third GABA designer medication. It blocks the reuptake of GABA in the synaptic area to be metabolized, therefore increasing GABA concentration, reducing brain excitation. It is mostly used as an adjunct for partial seizures, but may be effective in other seizure types as well. Generally it is well tolerated and was never reported to cause serious side effects. Unfortunately it has a poor effect on infantile spasm treatment and cannot be a substitute to Sabril as previously hoped.
An effective adjunct medication for partial seizure control, this one has no serious side effects reported. It currently has limited experience in the United States and has not been approved for children yet. For resistant partial seizures however, this medication should be attempted before resorting to invasive managements.
It come in 100mg capsules and is effective for the treatment of both partial and generalized seizures. It is very effective in absence seizure control and may substitute the use of Depakote in some of the absence seizures resistant to Zarontin or in those who have both absence and generalized convulsive seizures. Generally well tolerated, but in some children is causing extreme drowsiness. Zonegran is usually well tolerated in adults and may cause some rare but serious hematological side effects.