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Mood Disorders
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Madeleine A. Becker, Tal E. Weinberger, Leigh J. Ocker
In summary, valproic acid should generally not be used during pregnancy or in women of childbearing potential. In 2013, the FDA issued a drug safety communication stating that valproic acid is contraindicated for the treatment of migraine during pregnancy and that it should “only be prescribed if other medications are not effective in treating the condition or are otherwise unacceptable” for the treatment of epilepsy and bipolar disorder. Women of childbearing age must be informed of the increased risk for decreased IQ in children exposed to valproate in utero [146]. In 2018, the European Commission approved a ban on the use of valproate-containing medications for migraine and bipolar disorder during pregnancy and a ban on using these medications to treat epilepsy during pregnancy “unless there is no other effective treatment available.” Women of childbearing potential are required to be enrolled in a pregnancy prevention program before valproate can be prescribed [147].
Epilepsy
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Donald C. Barr, Andres M. Kanner
At the completion of the benzodiazepine load, and within 30 minutes of the start of therapy, the patient is concurrently started on a second-line therapy for prevention of withdrawal. Most algorithms suggest: Levetiracetam at a dose of 40–60 mg/kg.Lacosamide at a dose of 400–600 mg/day.Valproic acid at a dose of 30–40 mg/kg, if seizures continue, an additional 10 mg/kg may be given.Phenytoin (usually administered as fosphenytoin due to the lower risk of cardiovascular side effects) at 20 mg/kg loading dose.
Glutaric aciduria (type I)
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Riboflavin, as the coenzyme of the dehydrogenase, has appeared logical, and 100–300 mg/day have been used [69], but without clear evidence of therapeutic effect. Riboflavin was pronounced ineffective by the international consortium [17, 69]. Low concentrations of GABA in the basal ganglia led to the use of the GABA analog 4-amino-3-(4-chlorphenyl)butyric acid (baclofen, Lioresal); results have usually not been impressive, but improvement was reported in two of three patients in a double-blind controlled study given 2 mg/kg per day [9]. Diazepam (0.1–1 mg/kg daily) is commonly used to reduce involuntary movements and improve motor function. Use and dosage are limited by worsening of axial hypotonia. Trihexyphenidyl can be efficacious and can be used safely in adolescence in high dosage for segmental and generalized dystonia. Botulinum toxin and intrathecal baclofen are valid additions for focal dystonia or very severe dystonia, especially if accompanied by spasticity [69]. Valproic acid has been recommended, but most feel this drug is contraindicated [3, 69].
Efflux pump inhibitors as a promising adjunct therapy against drug resistant tuberculosis: a new strategy to revisit mycobacterial targets and repurpose old drugs
Published in Expert Review of Anti-infective Therapy, 2020
Liliana Rodrigues, Pedro Cravo, Miguel Viveiros
Valproic acid, or valproate, is a fatty acid derivative and anticonvulsant used in the treatment of epilepsy and bipolar disorders [132]. This drug has been also investigated for neuroprotective, anti-manic, and anti-migraine effects. Currently, it is a compound of interest in oncology drug research for its anti-proliferative effects and is the subject of many clinical trials. The mechanism of action of valproate is relatively unknown, but it is suggested that the drug’s action is a result of several pathways: i) inhibition of succinic semialdehyde dehydrogenase and increasing GABAergic neurotransmission; impact on fatty acid metabolism, which alters membrane fluidity; and noncompetitive inhibition of brain microsomal long-chain fatty acyl-CoA synthetase, which decreases available arichidonyl-CoA, a substrate in the production of inflammatory prostaglandins [133–135]. Valproate has been previously tested in M. tuberculosis. In 2015, Schieber et al. demonstrated that this drug stimulates the autophagosome formation in vitro and, in 2018, Rao and collaborators showed that it improves the action of isoniazid and rifampicin in the macrophage [136,137]. However, the specific target in M. tuberculosis has not been identified to date. Our study predicted a possible acyl-CoA dehydrogenase FadE19 (Rv2500c) as a potential M. tuberculosis target.
Moving beyond sodium valproate: choosing the right anti-epileptic drug in children
Published in Expert Opinion on Pharmacotherapy, 2019
Ganna Balagura, Giulia Iapadre, Alberto Verrotti, Pasquale Striano
Sodium valproate (VPA) is an established and widely used antiseizure drug [1] on the market for the treatment of both generalised and focal seizures in adults and children. The broad spectrum of this drug has been shown in preclinical and clinical studies, although no single mechanism of action does fully account for the different clinical indications and the wide spectrum of efficacy of this drug [2]. However, over the past few years, there has been increasing evidence that intake of valproic acid during pregnancy is associated with a significant risk of dose-dependent teratogenic effects and impaired postnatal cognitive development in children. Because of this risk, valproic acid should not be used as a first-line drug in women of childbearing potential whenever equally or more effective alternative drugs are available. After VPA, the history of antiepileptic drugs (AEDs) has already reached the third generation and more AEDs are expected to emerge. However, there are many issues concerning AEDs therapy, especially in the pediatric population, given the variability of pharmacokinetics and of the impact of adverse effects during development [3]. We reviewed the current use and the future role of VPA in children as well as the possible monotherapy alternatives to this drug. We also discussed some critical points about the choice of AEDs in the pediatric population, including lack of randomized-controlled trials (RCTs), need for comparative studies, and individualized treatment.
Usefulness of multiple electrode aggregometry as a screening tool for bleeding disorders in a pediatric hospital
Published in Platelets, 2019
Thorsten Haas, Melissa M. Cushing, Stephanie Varga, Séverine Gilloz, Markus Schmugge
Valproic acid has been extensively used in the management of childhood epilepsy. Unfortunately, it can potentially induce a variety of hemostatic abnormalities; with only some of them linked to mild to severe bleeding complications in the past [30,31]. In a prospective study of 24 children newly diagnosed with epilepsy treated with valproic acid, valproic acid led to a decreased platelet count (most frequent finding), and a decrease in factor VII activity, factor VIII activity, and fibrinogen plasma levels [30]. Other studies have demonstrated that valproic acid can cause VWD, decreased factor XIII activity, impaired platelet aggregation, prolongation of the bleeding time, as well as prolonged closure times of PFA-100 [31–36]. Interestingly, of the three of the children diagnosed with a valproic acid-induced bleeding disorder in our study, two had abnormal MEA results. This is in contrast to a recently published animal study where the administration of valproic acid did not have an impact on MEA results in healthy animals [37]. It should be noted that due to the lack of a clear definition for valproic acid-induced coagulopathy, the diagnosis used in our study was based on any abnormality of LTA or PFA-100 in the presence of valproic acid intake. The role of the individual platelet function tests for the diagnosis of a valproic-acid induced bleeding disorder needs to be further studied.