One of the most common concerns of patients and parents of children who are receiving

anti-epileptic drugs is the effect of drugs on school or work performance, memory, mood, and behaviour. Anti-epileptic drugs may cause some initial drowsiness, or changes in mood and behaviour, as the drug is being started, but these effects usually wear off. The older anti-epileptic drugs such as phenobarbitone and phenytoin have been shown to reduce a patient’s concentration or attention span and therefore cause an impairment in memory. This in turn can adversely affect learning and the ability to do certain tasks. These problems are less likely to occur with drugs such as carbamazepine, sodium valproate, vigabatrin, and lamotrigine, although it is impossible to guarantee that they have no effect. It is often difficult to determine whether a problem with either learning or behaviour is definitely due to a drug. A number of patients, as well as having epilepsy, may also have learning and behavioural difficulties as another manifestation of the brain problems that are causing epilepsy. A careful analysis of the story often shows that these difficulties appeared before any drug treatment was started, and that the drugs are not responsible.

Phenytoin has an unfortunate effect on the gums, which tend to thicken and grow down between the teeth. This can usually be kept at bay by twice daily brushing upwards and downwards with a medium bristle tooth brush. If necessary a dentist can push back the gums or remove the excessive tissue. This overgrowth of gum tissue is reflected in subtle changes in the lips and facial skin, which may become slightly ‘fleshy’. Phenytoin and barbiturates predispose to acne of the face and back, and may cause some slight excess of facial hair. These cosmetic effects may be a reason to avoid using these drugs in young people. Sodium valproate, on the other hand, may cause hair to fall from the scalp in a very small number of people. Regrowth of hair usually occurs even without stopping the drug.

There are a number of other side-effects of anti-epileptic drugs. Phenobarbitone seems to affect the shoulder joint in a few people, so that it becomes stiff and painful. In others, changes in the tendons in the hands and connective tissue of the palms leads to a contracture (Dupuytren’s contracture) of the hands. Phenytoin may cause an excessive metabolism of the body’s vitamin D supplies, which may lead to rickets, in the absence of adequate diet or sunlight (which helps form vitamin D).

Finally, and importantly, there is the issue of the effect of anti-epileptic drugs on the developing baby—a particular concern to women with epilepsy. There is a slight increase in the occurrence of fetal abnormalities of mothers who have epilepsy. From the analysis of a large number of patients, it is clear that much of this increase is due to anti-epileptic drugs, particularly phenobarbitone and phenytoin. Phenytoin produces a number of abnormalities including a characteristic face, a cleft-(hare) lip or palate, very small and under-developed finger and toe nails, heart defects, spina bifida, and learning difficulties. It must be stressed that this does not occur in the babies of all women taking phenytoin in pregnancy. It will occur in only about 5-10 out of every 100 mothers who have epilepsy and are taking phenytoin, but this risk is about two or three times the risk in women who do not have epilepsy. Sodium valproate, and to a lesser extent carbamazepine, may also cause spina bifida, a malformation of the vertebrae and spinal cord. This risk of sodium valproate causing spina bifida is 1-2 per cent. It is important to realize that these malformations arise early in pregnancy—perhaps even before the mother realizes that she is pregnant. For this reason it is wise to discuss pregnancy and anti-epileptic drugs with doctors before conception. During the pregnancy the growth and development of the baby can be monitored closely by detailed ultrasound examinations, which will usually detect major heart abnormalities or severe spina bifida.

Finally, it is also important to realize that if a mother has frequent generalized tonic-clonic (grand mal) seizures during pregnancy this may actually cause more harm to the baby than the drugs themselves—either by direct injury to the abdomen as the mother falls, or by the seizure preventing a sufficient oxygen supply in the mother’s, and therefore in the baby’s, blood. Although both of these circumstances are rare, they may occur, and because of this it is recommended that anti-epileptic drugs are taken during pregnancy, but that the blood levels are closely monitored. However, it must be stressed that the decision must be taken by patient and doctor together in equal partnership.

The issue of side-effects or toxicity is frequently undervalued by doctors.

Minimal side-effects (as defined by an individual or parent of a child and not by the doctor) may be acceptable providing seizure control is good. Major side-effects with or without seizure control are usually unacceptable. What may be acceptable to one patient (or family) may be unacceptable to another. The control of seizures in patients with difficult epilepsy may be improved or achieved by doses of drugs that may cause significant adverse effects. In many of these patients a compromise has to be reached, and a narrow line steered between controlling the seizures without producing excessive sedation or loss of other abilities.

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