Increase of Human Plasma GABA by Sodium Valproate

Löscher, Wolfgang; Schmidt, Dieter

doi:10.1111/j.1528-1157.1980.tb04314.x

Cited by 83 publications

(32 citation statements)

References 17 publications

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“…Moreover, it was previously suggested that VPA may influence thyroid function, because the drug combinations that cause the most marked reductions in thyroid hormones and the most marked increases in TSH are those comprising VPA and an enzyme-inducer, notably CBZ (19,29). The high levels of serum basal TSH observed in VPA monotherapy patients and CBZ-VPA combination-therapy patients may be due to the y-aminobutyric acid (GABA) ergic properties of VPA (42), because GABA inhibits somatostatin release, and somatostatin inhibits TSH secretion Our PB-treated series is the largest reported to date in a pediatric population, although the childadult series of Tanaka et al (24) was larger. We observed decreases in the levels of T, and FT,, and no change in the level of TSH, as in previous studies (13,24,29).…”

Section: Discussionmentioning

confidence: 99%

Long‐Term Treatment of Children with Epilepsy with Valproate or Carbamazepine May Cause Subclinical Hypothyroidism

Eirís-Puñal¹,

Río-Garma²,

Río-Garma

et al. 1999

Epilepsia

103

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Summary:Purpose: The aim of the study was to evaluate serum thyroid hormone balance in children receiving long-term therapy with carbamazepine (CBZ), valproate (VPA), and phenobarbital (PB).Methods: We determined serum levels of triiodothyronine (TJ, thyroxine (TJ, free thyroxine (FT,), thyroxine-binding globulin (TBC), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months. In view of TSH values, three categories of subclinical hypothyroidism were considered: I, TSH greater than the control-group mean + 2 SD (4.37 mIUL in our study) and <6 mIU/L; 11, TSH between 6 and 12 mIUL; and 111, TSH >I2 mIU/L.Results: In all treated groups, mean T, and f14 levels were lower than in the control group, whereas the CBZ-and VPAtreated children additionally showed reduced mean T, and TBC levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normalrange maximum, by comparison with only 3.6% of healthy children. The increase in TSH levels was particularly marked in VPA-treated children, accounting for 26% of patients with subclinical hypothyroidism. Conclusions: Our results, in contrast to previous reports, suggest that CBZ and particularly VPA may induce subclinical hypothyroidism. This suggests a need for careful monitoring of TSH levels in children receiving CBZ or VPA.

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Section: Discussionmentioning

confidence: 99%

Long‐Term Treatment of Children with Epilepsy with Valproate or Carbamazepine May Cause Subclinical Hypothyroidism

Eirís-Puñal¹,

Río-Garma²,

Río-Garma

et al. 1999

Epilepsia

103

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“…g-Aminobutyric acid inhibits the release of somatostatin, which inhibits TSH secretion. 13 The causal association between valproate and subclinical hypothyroidism has been suggested by Eirís-Puñal and colleagues. 4 They observed normalization of elevated TSH levels after the valproate was changed to ethosuximide in one case.…”

Section: Prevalence Of Subclinical Hypothyroidism In Children With Epmentioning

confidence: 94%

Evaluation of Subclinical Hypothyroidism in Ambulatory Children With Controlled Epilepsy on Valproate Monotherapy

et al. 2011

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There are conflicting reports in the literature about the influence of valproate on thyroid function. A cross-sectional study was performed to determine the prevalence of subclinical hypothyroidism in ambulatory children aged 3 to 15 years with controlled epilepsy receiving valproate monotherapy for at least 6 months. Fifty-seven consecutive children with controlled epilepsy on valproate monotherapy and 52 healthy age- and sex-matched control children were studied. Thyroid-stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, and serum valproic acid levels were measured. There was a significantly high (P = .012) prevalence of subclinical hypothyroidism (26%) in those receiving valproate monotherapy compared with healthy controls (7.7%). Median duration of valproate therapy was significantly higher (P = .039) in the subclinical hypothyroidism group (21 months, range 6-36) compared with those without subclinical hypothyroidism (14 months, range 6-25). Results of the present study suggest higher prevalence of subclinical hypothyroidism in children with controlled epilepsy on long-term valproate monotherapy.

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“…Berrettini et al 98 reported that lithium increased the CSF and plasma levels of GABA in euthymic bipolar patients, although they did not replicate these findings in a second larger study. 102 Valproate has been shown to increase plasma GABA levels in human individuals, [208][209][210] suggesting that it enhances brain GABA activity. Petty et al 131 reported that higher pretreatment GABA plasma levels predicted response to valproate in acute manic patients, and did not correlate with symptom severity.…”

Section: Gabaergic Modulation In the Treatment Of Mood Disordersmentioning

confidence: 99%