A controlled study of folic acid in epilepsy

IT HAS BEEN KNOWN for some time that macrocytosis and macrocytic anemia may occur during the course of anticonvulsant medication in epilepsy and that this is somehow related to a deficiency of folic acid.l.2 However, more recently, attempts have been made to relate folate deficiency to various neuropsychiatric disturbances ranging from dementia3 to schizophrenia-like psychoses, failure of seizure control, and even spinal cord and cerebellar disease.4,5 In view of the large numbers of epileptics currently receiving treatment with anticonvulsant drugs, it is of great practical importance to know whether folate deficiency is an integral part of seizure control and whether correction of this deficiency may result in the potentially fatal complication of status epilepticus, as has been suggested.6 Since most of the evidence for this association rests upon sporadic case reports, we have performed a controlled drug trial comparing the number of fits occurring during folic acid administration to those occurring during placebo administration. In view of the interrelationship between vitamin B,, and folic acid and since there have been reports of a fall in serum vitamin B,, levels after folate administration,T we also measured serum levels of this vitamin before and after folic acid administration. It was originally planned to perform a double-blind crossover study on each patient using placebo versus active folate. However, since man’s ability to store folate is not accurately known, the possibility of continuing release of active folate during the placebo period in patients receiving folate prior to placebo could not be excluded. It was, therefore, decided to give all patients placebo for the first three months and folic acid for the subsequent three months. By allowing the patients, who were unaware of this substitution, to record their own seizures, observer bias was excluded.