HDL and phenytoin

Last reviewed 05/2023

The effects of different anticonvulsant drugs on lipid profiles is inconsistent between studies. However there is a reasonable evidence base suggesting that HDL levels may be raised with phenytoin therapy. Also carbamazepine seems to increase total cholesterol and HDL levels.

Phenytoin and HDL cholesterol

• phenytoin use in patients with low HDL
  • a small study the use of phenytoin with placebo in patients with a low HDL (1)
    • compared with dietary baseline, phenytoin-treated subjects experienced significant paired percent increases in total HDL-C (12.4%; P<.01), an effect confined to the HDL2 subfraction (137%; P<.01). The paired percent increases in HDL-C and HDL2 levels remained significant after adjustment for placebo (P<.05, P<.025, respectively). There were no significant differences in the paired percent changes from dietary baseline in total cholesterol, triglyceride, or LDL cholesterol levels between placebo and phenytoin-treated groups
• there is evidence of increased HDL levels in TIA patients who were treated with phenytoin (2)

Other anticonvulsant drugs and lipid levels

• a study in children revealed (3):
  • carbamazepine
    • serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations increased after 3 months of treatment with carbamazepine and remained high after one year.
  • phenobarbitol
    • serum total cholesterol levels increased after 3 months of treatment with phenobarbital and remained high after one year
  • valproic acid
    • serum lipid concentrations did not change during valproic acid therapy
• a study in adults revealed (4)
  • compared with controls
    • patients on carbamazepine showed significant higher TC, HDL-c, and LDL-c and non significantly higher TG values
    • patients on phenobarbital showed no statistically significant differences in TC, HDL-c, LDL-c and TG values
    • patients on phenytoin showed significantly higher LDL-c values and non-significant differences in TC, HDL-c and TG values
    • patients on valproate showed significantly lower TC, LDL-c and TG values and non-significant differences in HDL-c values. Changes in serum lipid profiles did not correlate with drug plasma levels.

Reference:

• 1) Miller M et al.. A prospective, randomized trial of phenytoin in nonepileptic subjects with reduced HDL cholesterol. Arterioscler Thromb Vasc Biol. 1995 Dec;15(12):2151-6
• 2)Kaste M et al. Increase of low serum concentrations of high-density lipoprotein (HDL) cholesterol in TIA-patients treated with phenytoin. Stroke. 1983 Jul-Aug;14(4):525-30.
• 3) Yilmaz E et al. . Serum lipid changes during anticonvulsive treatment serum lipids in epileptic children. Acta Neurol Belg. 2001 Dec;101(4):217-20
• 4) Nikolaos T et al. The effect of long-term antiepileptic treatment on serum cholesterol (TC, HDL, LDL) and triglyceride levels in adult epileptic patients on monotherapy. Med Sci Monit. 2004 Apr;10(4):MT50-2.
• 5) Luoma PV et al. Plasma high-density lipoprotein cholesterol and hepatic cytochrome P-450 concentrations in epileptics undergoing anticonvulsant treatment. Scand J Clin Lab Invest.. 1980;40:163-1