AIIMS November 2011 – MCQ 20

A 4 month pregant lady on treatment with valproate regularly asked for your advice regarding taking the drug during pregnancy. What is the best course of action?
A. Immediately taper off valproate and start lamotrigine
B. Change to carbamazapine
C. Continue valproate and monitor blood levels
D. Slowly taper dose of valproate

Correct answer : C. Continue valproate and monitor blood levels

The period of organogenesis is over and hence there is not much risk of teratogenecity. And changes to anti epileptic drugs should be done before conception to avoid seizure risk during pregnancy. Due to altered plasma protein binding during pregnancy, it is recommended that blood levels are measured to maintain a therapeutic range. (Current diagnosis and Treatment). Although Williams state that blood level monitoring is not very useful, it also states that Free drug level monitoring is useful, though not widely available. Harrison also supports continuing the present medication.

In general, anticonvulsant medication should be maintained at the lowest dosage associated with seizure control. Although some clinicians routinely monitor serum drug levels during pregnancy, antenatal serum drug levels may be unreliable because of altered protein binding. Free or unbound drug levels, although more helpful, are not widely available. Lander and Eadie (1991) reported that seizure control is not improved by routine drug level monitoring. For these reasons, drug levels may be measured only following seizures or if noncompliance is suspected. (Williams 22nd)

Treatment of epilepsy should consist of the medication that has been most beneficial for the patient and at the lowest possible dose to maintain seizure control with some caveats. Some antiepileptic agents are more likely to cause birth defects than are others, and attempts to change medications should be made prior to conception. During pregnancy, anticonvulsant levels change as a result of decreased protein binding, increased plasma volume, and alterations in the absorption and excretion of drugs. In addition, lamotrigine, phenytoin, phenobarbital, and carbamazepine have an increased plasma clearance that probably is related to high hepatic metabolism. These factors most often lead to low antiseizure plasma levels. Noncompliance, morning sickness, and hyperemesis gravidarum are other reasons for low drug levels. Therefore, blood level measurements of antiseizure medications are used to monitor and maintain a therapeutic range. Levels should be checked at least each trimester and prior to delivery. More frequent monitoring may be needed. Because of decreased protein binding, serum free drug levels rather than routine serum levels will be more accurate.(Current Diagnosis & Treatment Obstetrics & Gynecology, Tenth Edition)

Since the potential harm of uncontrolled convulsive seizures on the mother and fetus is considered greater than the teratogenic effects of antiepileptic drugs, it is currently recommended that pregnant women be maintained on effective drug therapy. When possible, it seems prudent to have the patient on monotherapy at the lowest effective dose, especially during the first trimester. For some women, however, the type and frequency of their seizures may allow for them to safely wean off antiepileptic drugs prior to conception. Patients should also take folate (1–4 mg/d), since the antifolate effects of anticonvulsants are thought to play a role in the development of neural tube defects, although the benefits of this treatment remain unproved in this setting. (Harrison 18th)

Fetal valproate syndrome:
Valproate causes birth defects: exposure during pregnancy is associated with about three times as many major anomalies as usual, mainly spina bifida and, more rarely, with several other defects, possibly including a “valproate syndrome”. Characteristics of this valproate syndrome include facial features that tend to evolve with age, including trigonocephaly, tall forehead with bifrontal narrowing, epicanthic folds, medial deficiency of eyebrows, flat nasal bridge, broad nasal root, anteverted nares, shallow philtrum, long upper lip and thin vermillion borders, thick lower lip and small downturned mouth. (Wikipedia)