Dibenzazepine Anticonvulsants

Anticonvulsants/Nutrient Depletion:

  • BiotinBiotin: Human study indicates that long-term administration of some anticonvulsants may accelerate biotin catabolism, but the indicators of biotin status conflict (9523856). The anticonvulsants phenytoin (Dilantin?), primidone (Mysoline?), carbamazepine (Tegretol?), phenobarbital (Solfoton?), and possibly valproic acid have been associated with reduced blood levels of biotin. This is due to reduced gut absorption of biotin and increased urinary excretion. Testing of biotin blood or urine levels should be considered in individuals using these drugs chronically, and biotin supplementation may be necessary if deficiency is found.
  • CalciumCalcium: Secondary sources cite that anticonvulsants (phenytoin, fosphenytoin, phenobarbital, and carbamazepine) may decrease calcium absorption by increasing metabolism of vitamin D. According to human trial, anticonvulsant intake may lead to hypocalcemia and softening of the bones (osteomalacia) (4776883).
  • CarnitineCarnitine: Decreased serum carnitine has been noted in children using anticonvulsants (phenobarbital, phenytoin, carbamazepine) (1941389).
  • CopperCopper: Based on human study, anticonvulsants like valproic acid may cause depletion of copper (15621922, 1592036, 8852271). In other human study, chronic administration of anticonvulsants including phenytoin, phenobarbital, carbamazepine, and valproic acid does not produce copper deficiency (14642999). Based on study in epileptic patients on long-term anticonvulsant therapy, carbamazepine monotherapy induced fewer disturbances in copper metabolism than phenytoin monotherapy (9579288).
  • FolateFolate: Evidence from human trials indicate that carbamazepine (Tegretol?) may reduce serum folate levels, but megaloblastic anemia has not been reported (1548649). Phenobarbital (Luminal?) and primidone (Mysoline?) may reduce serum folate levels, occasionally leading to megaloblastic anemia (usually in people with low dietary folate intake), and possibly contributing to neurological side effects, mental changes, and cerebral atrophy. Based on human and animal evidence, pregnant women taking carbamazepine, phenobarbital, or primidone may be especially at risk from reduced folate levels (1548649, 3606631).
  • Niacin/NiacinamideNiacin/Niacinamide: Secondary sources indicate that anticonvulsants may deplete niacin, although the mechanism is unknown.
  • PhosphorusPhosphorus: Based on human evidence, some anticonvulsants (including phenobarbital and carbamazepine) may lower phosphorus levels and increase levels of alkaline phosphatase (1161362).
  • RiboflavinRiboflavin: Based on human evidence, phenytoin (DIlantin?) may alter riboflavin levels (1121974).
  • SeleniumSelenium: Administration of valproic acid for one week produced depletion selenium in plasma of rats and a one-third reduction of hepatic selenium (6435012).
  • ThiaminThiamin: According to secondary sources, reduced levels of thiamine have been reported in individuals taking phenytoin for extended periods of time. However, thiamin supplementation beyond the Recommended Daily Allowance is not currently universally recommended in patients taking phenytoin.
  • Vitamin B6/pyrodoxineVitamin B6/pyrodoxine: One controlled study revealed that taking anticonvulsant agents may dramatically reduce blood levels of vitamin B6 (10080517).
  • Vitamin B12Vitamin B12: Anticonvulsants have been associated with reduced vitamin B12 absorption, and reduced serum and cerebrospinal fluid levels in human studies (18190464, 6607408). Phenytoin (Dilantin?), phenobarbital, and primidone (Mysoline?) have been associated with reduced vitamin B12 absorption and reduced serum and cerebrospinal fluid levels in some patients. This may contribute to the megaloblastic anemia, primarily caused by folate deficiency, associated with these drugs. It is also suggested that reduced vitamin B12 levels may contribute to the neuropsychiatric side effects of these drugs. Secondary sources indicate that patients may be encouraged to maintain adequate dietary vitamin B12 intake and that folate and vitamin B12 status should be checked if symptoms of anemia develop.
  • Vitamin D/calciferolVitamin D/calciferol: Based on human evidence, decreased vitamin D levels may occur with the use of certain anti-seizure drugs, as they may induce hepatic microsomal enzymes and accelerate the conversion of vitamin D to inactive metabolites (18700645, 18686472, 17016548).
  • Vitamin EVitamin E: Based on human evidence, anticonvulsant drugs such as phenobarbital, phenytoin, or carbamazepine may decrease blood levels of vitamin E (6213919).
  • Vitamin KVitamin K:According to a multicenter study, vitamin K deficiency increased in neonates exposed to anticonvulsant drugs prenatally (8456903). According to a clinical trial, antenatal vitamin K1 treatment decreased the frequency of vitamin K deficiency in neonates of mothers on anticonvulsant therapy (8456897).
  • ZincZinc: Based on animal evidence, administration of valproic acid may deplete plasma zinc (6435012).