Studies on Deficiency and Absorption of Folates in Patients on Anticonvulsant Drugs

Abstract

Summary The incidence of macrocytosis and low serum folate levels has been estimated in 115 mental hospital patients on anticonvulsant drug therapy and in 48 mental hospital control patients. Low serum folate levels were found in 36·1% of the patients treated with anticonvulsants. Of the patients on anticonvulsants, 14·6% had red cell macrocytosis, and the incidence of macrocytosis was significantly higher in female than in male patients. The mental hospital patients not on anticonvulsants who were used as controls had mean serum folate values significantly below that of the normal, non‐hospitalized controls. Attention is drawn to the influence of the diet on normal folate ranges, which must be taken into account during their assessment. The fact that a combination of factors is probably necessary to produce a frank megaloblastic change in anticonvulsant‐drug‐treated patients could account for the relative infrequency of megaloblastosis among these patients. It is believed that, in case of anticonvulsant drug therapy, a borderline folate diet often interacts with the mild drug folate inhibition. Folic acid absorption tests, carried out on 19 patients on anticonvulsant therapy with subnormal folate levels, showed slightly decreased absorption values at two hours after the oral test dose but no difference at three hours. The significance of these findings is discussed, and attention is drawn to possible mechanisms of mild malabsorption of folates in patients on anticonvulsant drugs.

Folic Acid Absorption Test in Various Clinical Conditions

“…This is not the case because, as In a previous study [16] FAAT, carried out in 19 patients on anticonvulsant therapy for at least 6 months, showed decreased ab sorption values at 2 h after the oral test, but no difference at 3 h. In our cases decreased absorption values were still present at 210 min after the oral test. The difference between our results and those of Ibbolson et al [16] seems to be explained on the basis of the duration of therapy: our patients had been taking DPH for more than 6 years (19.8 ± 9.02. mean ± SD).…”

“…All medication was withdrawn in all patients under study 16 Table I gives the age of the patients and the serum folate levels prior to and during the FAAT. The one-way analysis of variances [22] showed no statistically significant differ ences in the age of subjects amongst the six groups (F = 2.31. df = 5.66).…”

“…The relatively high incidence of abnormal 5-hour glucose tolerance curves in our patients with folate-responsive neuropsy chiatrie symptoms raised the question of the relationship between folate and carbohydrate metabolism [1], There have been positive [6,9,12,16] and negative studies [10,17] regarding the effects of diphenylhydantoin (DPH) on folate ab sorption in humans. It is, however, generally accepted that DPH inhibits folate absorption at the intestinal level [9], Therefore, we considered it useful to carry out a folate absorption test in the following groups of subjects: normal controls, patients with disorders of carbohydrate metabolism, epileptic patients receiving DPH, patients with gastroduodenal disease and patients with atrophy of jejunal mucosa.…”

Depression in Patients With Epilepsy

“…Reynolds' (1976) view is that "severe folate deficiency gradually leads to apathy, depression, social withdrawal and ultimately dementia ". Contribut~ry factors to low FA in psychiatric patients may be due to <L.-rug treatment, including antidepressants in 79% physical illness in 18.6%, and malnutrition in 22.1% (Carney and Sheffield 1970): no such extrinsic factors were found in 25°/o. Other authors (Ibbotson et al 1967;Reynolds et al 1970;Reynolds 1976) also emphasise the dietary importance of FA deficiency in depression and psychotic illness.…”

Mindert eine Folsäuresubstitution die Teratogenität von Antiepileptika?

“…Der Mechanismus, der der Reduktion der Folatkonzentrationen durch Antiepileptika zugrunde liegt, ist jedoch nicht bekannt. Eine Vielzahl von Mechanismen, durch die diese Medikamente eine Folatminderung induzieren könnten, wurde postuliert: die Induktion von Leberenzymen [42], die Beeinträchtigung der Folatabsorption [34], eine kompetitive Interaktion zwischen Folatkoenzymen und Medikamenten [29] und zunehmende Anforderungen an Folat als einem Kofaktor in der Hydroxylierung von Antikonvulsiva [35].…”