Antiepileptic therapy, folate deficiency, and psychiatric morbidity: a general practice survey

The effect of anticonvulsant drugs on folate metabolism and mental symptoms has been investigated extensively in hospital-based studies, but never before in the community or general practice setting. Blood count, serum vitamin B12, red blood cell (RBC), and serum folate were measured in a sample of 82 adult epileptic patients drawn from 5 group practices (14 general practitioners) in southeast London. All patients were receiving antiepileptic medication at the time of examination and were interviewed with a standardized measure of psychopathology. Serum folate values below the lower limit of the normal range (3-15 micrograms/L) were obtained in 9 (10.9%) subjects, and in 50 (60.9%) patients, serum folate concentrations were less than the mean (6.02 micrograms/L) for the whole sample. Macrocytosis was detected in 20 (24.3%) patients. RBC and serum folate levels were significantly correlated with one another, but not with vitamin B12 concentrations. Levels of RBC and serum folate were significantly lower in patients on polytherapy (n = 40) than in those on monotherapy (n = 42); the folate concentrations were also significantly lower in the group with psychiatric morbidity. The association between folate deficiency and affective morbidity was demonstrated for depression but not for anxiety. There was no relationship between serum vitamin B12 and psychiatric disturbance. These findings are discussed in the light of relevant literature regarding the mechanism of action of anticonvulsant drugs in folate depletion and the neuropsychiatric sequelae.