Hormonal Valproate

As noted above, many of the AEDs induce hepatic microsomal enzyme systems and thus reduce the effectiveness of hormonal contraceptives. Women taking AEDs that may reduce the effectiveness of hormonal contraceptives should be encouraged to also use other forms of birth control. Due to induction or inhibition of sex hormone metabolism and changes in binding of hormones to sex hormone binding globulin, some AEDs may reduce fertility. For example, valproate has been associated with a drug-induced polycystic ovarian syndrome. Women who experience difficulties with fertility should seek the advice of health care professionals with expertise in fertility. 

Fatty acid beta-oxidation Inhibition by valproate, tetracyclines, nonsteroidal antiinflammatory drugs, antianginal cationic amphiphilic drugs, female sex hormones, CoA depleters such as valproate and salicylate... 

Porsteinsson AP, Tariot PN, Erb R, et al An open trial of valproate for agitation in geriatric neuropsychiatric disorders. Am J Geiiatr Psychiatry 5 344-351, 1997 Posener JA, Schildkraut JJ, Williams GH, et al Acute and delayed effects of corticotropin-releasing hormone on dopamine activity in man. Biol Psychiatry 36 616-621, 1994... 

Normal growth hormone concentrations are found in car-bamazepine-treated patients (94). Growth hormone secretion in response to levodopa stimulation was not affected by carbamazepine or phenobarbital, whereas phenytoin and anticonvulsant polytherapy caused an increase in growth hormone concentration, and valproate a fall at varying times after the administration of levodopa (95). Pubertal growth arrest has been described in a 12-year-old girl who had taken valproate for 18 months (SED-13,152). 

Carbamazepine, phenobarbital, phenytoin, and anticonvulsant polytherapy increased both basal and stimulated concentrations of prolactin, whereas valproate did not (95). However, in other studies, prolactin was unchanged (94). In boys, phenobarbital lowered baseline LH and FSH concentrations and their response to releasing hormone baseline prolactin concentration was raised in comparison with healthy children, and the response of prolactin concentrations to stimulation was impaired (99). 

Total and free (unbound) thyroxine can be reduced by phenytoin and carbamazepine, but free triiodothyronine is normal or only slightly reduced. Thyroid-stimulating hormone is normal or only slightly altered and patients remain clinically euthyroid (94,108). Reductions in the concentrations of some thyroid hormones are probably related to enzyme induction the concentrations return to normal after substituting carbamazepine with oxcarbaze-pine, a less potent enzyme inducer (109). Hypothyroidism has been rarely described in patients taking phenytoin or carbamazepine (110). In contrast to earlier reports, there were no changes in thyroid hormones during treatment with valproate in a later study (111). 

In 1705 patients, aged 65 years or over, who had recently started to take lithium, identified from the 1.3 million adults in Ontario receiving universal health care coverage, the rate of treatment with thyroxine was 5.65 per 100 person-years, significantly higher that the rate of 2.70/100 person-years found in 2406 new users of valproate (629). Of 46 adults taking lithium in a psychiatric clinic, 17% developed overt hypothyroidism while 35% had subclinical hypothyroidism (raised concentrations of thyroid stimulating hormone, TSH) (630). 

Rattya J, Pakarinen AJ, Knip M, Repo-Outakoski M, Myllyla VV, Isojarvi JI. Early hormonal changes during valproate or carbamazepine treatment a 3-month study. Neurology 2001 57(3) 440 1. 

Phenobarbitone, benzodiazepines Valproate, benzodiazepines, adreno-corticotrophic hormone Ethosuximide, valproate, benzodiazepines, acetazolamide... 

Treatment of tardive dyskinesia is often unsatisfactory, especially in severe cases. A large number of treatments have been proposed (SEDA-20,40), including antiparkinsonian drugs, benzodiazepines, baclofen, hormones, calcium channel blockers, valproate, propranolol, opiates, cyproheptadine, tryptophan, lithium, manganese, niacin, botulinum toxin, ECT, dietary control, and biofeedback training. In an open study, 20 patients (mean age 65 years) with severe unresponsive tardive dyskinesia (mean duration 44 months, mean exposure 52 months) were treated with tetrabenazine (mean dose 58 mg/day) (310). The mean score on the AIMS motor subset, determined from videotapes, improved by 54%. Sedation was the only subjective complaint. 

Polycystic ovary syndrome (polycystic ovaries, hjrper-androgenism, obesity, hirsutism, anovulatory cycles, and menstrual disorders) is more common in women with epilepsy. Valproate has been associated with alterations in reproductive hormonal function beginning in the first month of treatment. Serum androgen concentrations increase in patients taking valproate but the profile of hormonal changes is different in women and men (97). Animal studies have corroborated the adverse ovarian and endocrine effects of valproate (98). Four review articles have dealt with this reported adverse event, highlighting controversial views (99-102). 

Valproate caused a fall in growth hormone concentrations at varying times after the administration of levodopa (134). 

Bentsen KD, Gram L, Veje A. Serum thyroid hormones and blood fohc acid during monotherapy with carbamazepine or valproate. A controlled study. Acta Neurol Scand 1983 67(4) 235-41. 

Slc21a4) taurocholate, thyroid hormones Drugs AZT, MTX Drugs NSAIDs, furosemide, valproate... 

Koulu M, Lammintausta R, Kangas L, Dahlstrom S. The effect of methysergide, pimozide and sodium valproate on the diazepam-stimulated growth hormone secretion in man. J Clin Endocrinol Metab 1979 48 119-22. 

Clinical Effectiveness Unit guidelines on the management of hormonal contraceptives and drug interactions state that valproate does not induce liver enzymes and causes no reduction in ethinylestradiol or progestagens. The manufacturers of sodium valproate and valproate semi sodium state that valproate does not affect the efficacy of hormonal... 

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