Metabolic changes during treatment with valproate in humans: Implication for untoward weight gain

Breum, Leif; Astrup, Arne; Gram, Lennart; Andersen, T; Stokholm, K. H.; Christensen, Niels Juel; Werdelin, L.; Madsen, J.

doi:10.1016/0026-0495(92)90061-e

Cited by 94 publications

(63 citation statements)

References 21 publications

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“…At the >1,800-mg/day dosage level, the most commonly reported adverse events were somnolence, dizziness, and weight gain. Weight gain was reported by more patients taking concomitant VPA (7%) than any other AED (?2%), and may have been related more to VPA than to GBP administration (2,14).…”

Section: Concomitant Aeosmentioning

confidence: 99%

Safety and Tolerability of Gabapentin as Adjunctive Therapy in a Large, Multicenter Study

et al. 1999

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Summary:Purpose: To evaluate the tolerability and safety of gabapentin (GBP) as add-on therapy for seizure control.Merhods: Conducted in an outpatient setting and reflecting usual practice, this study compared tolerability of GBP dosages 5 1.800 versus > 1,800 mgiday, when these doses were required to achieve the most effective seizure control. Two analyses of adverse events are presented: tolerability and safety. In the tolerability analysis, each patient served as his or her own control to compare the occurrence of adverse events at GBP 11,800 versus > I ,800 mg/day. The safety analysis required patients to receive at least one dose of GBP and have a followup contact.Results: A total of 2,216 patients enrolled in this open-label, 16-week study and were evaluable for safety. Of these, 74.0% completed the 16-week study, and 28 1 met the tolerability criteria. Within these 28 1 patients, two mutually exclusive groups were compared (a) those reporting adverse events at only 5 1,800 mg/day (low dose); and (b) those reporting adverse events at only > I ,800 mg/day (high dose). Three adverse events (asthenia, headache, and dizziness) were observed in a statistically significantly larger number of patients at only the low dose than in the group reporting these same adverse events at only the high dose, suggesting that patients who tolerated GBP at 5 1,800 mg/day did not experience a significant increase in adverse events with dosages >1,800 mg/day. Overall, 10.6% of the 2,216 patients in the safety population prematurely withdrew because of adverse events, and 3.5% discontinued because of lack of efficacy. Safety and tolerability of GBP was rated as excellent or good for 78.5% of all patients.Conclusions: Gabapentin doses > I ,800 mg/day were as well tolerated as doses 51,800 mg/day and were not associated with more adverse events.

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Section: Concomitant Aeosmentioning

confidence: 99%

Safety and Tolerability of Gabapentin as Adjunctive Therapy in a Large, Multicenter Study

et al. 1999

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“…These studies show that weight gain occurs within the first ten weeks of treatment and is in the order of six kilograms (10,23). Weight gain during VPA therapy is associated with metabolic changes like a decrease in â-oxidation of fatty acids (18), increased insulin and insulin/glucose ratios (31), and increased leptin and insulin levels (120). The problem appears to be more common in females, it is not necessarily eliminated by caloric restriction, and it may lead to discontinuation of VPA therapy.…”

Section: Dose-related Side Effectsmentioning

confidence: 99%

Valproate: Past, Present, and Future

2003

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Preclinical studies have been carried out during the past four decades to investigate the different mechanisms of action of valproate (VPA). The mechanisms of VPA which seem to be of clinical importance include increased GABAergic activity, reduction in excitatory neurotransmission, and modification of monoamines. These mechanisms are discussed in relation to the various clinical uses of the drug. VPA is widely used as an antiepileptic drug with a broad spectrum of activity. In patients, VPA possesses efficacy in the treatment of various epileptic seizures such as absence, myoclonic, and generalized tonicclonic seizures. It is also effective in the treatment of partial seizures with or without secondary generalization and acutely in status epilepticus.The pharmacokinetic aspects of VPA and the frequent drug interactions between VPA and other drugs are discussed. The available methods for the determination of VPA in body fluids are briefly evaluated.At present, investigations and clinical trials are carried out and evaluated to explore the new indications for VPA in other conditions such as in psychiatric disorders, migraine and neuropathic pain. Furthermore, the toxicity of VPA, both regarding commonly occurring side effects and potential idiosyncratic reactions are described. Derivatives of VPA with improved efficacy and tolerability are in development.

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“…Circulating catecholamines increase in patients taking valproate, and this increase could decrease thermogenesis. Breum et al (69), however, did not find evidence for greater thermogenesis in their study of patients taking valproate. Short-term clinical studies have not provided support for any of the proposed mechanisms for weight gain in patients taking valproate.…”

Section: Aed Weight Lossmentioning

confidence: 76%

“…No change in appetite or thirst has been found in patients who gain weight with valproate (59,61). Breum et al (69) did not find any difference in total energy intake or macronutrient selection, energy expenditure, or thyroid hormones. The exact mechanism for weight gain with valproate requires additional study.…”

Section: Aed Weight Lossmentioning

confidence: 88%

Adverse Effects of Antiepileptic Drugs

Greenwood

2000

Epilepsia

108

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Summary:Because the efficacies of antiepileptic drugs (AEDs) are often equivalent, selection of an AED is often determined by adverse effects. Differences in methods for labeling adverse effects and in the adverse effect terms themselves, variations in the populations studied, and inconsistent classifications of adverse effects make it difficult to know how to use information on adverse effects to choose an AED. Effort is underway to develop more extensive and internationally acceptable descriptive terms for adverse effects. Comparison of adverse effects in patients taking AEDs with adverse events in control groups is helpful; however, data from controlled studies are often lacking for most AEDs. Because of these limitations, the clinician must adopt a preventative and early detection approach based on some general principles. This review outlines factors to consider for avoiding and detecting AED adverse effects. The occurrence of weight change with AEDs is reviewed extensively, serving to illustrate how the principle factors can be used to avoid and manage adverse effects and where there is need for better studies of the short-and long-term adverse effects of AEDs.

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Metabolic changes during treatment with valproate in humans: Implication for untoward weight gain

Cited by 94 publications

References 21 publications

Safety and Tolerability of Gabapentin as Adjunctive Therapy in a Large, Multicenter Study

Safety and Tolerability of Gabapentin as Adjunctive Therapy in a Large, Multicenter Study

Valproate: Past, Present, and Future

Adverse Effects of Antiepileptic Drugs

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