Gastrointestinal effects valproate

The therapeutic uses of valproate in psychiatric conditions have been reviewed (1,2). The major adverse effects in one study of 150 patients were tremor (9.3%), gastrointestinal effects (8.9%), drowsiness (8.6%), hair loss (7.9%), weight gain (6.9%), weakness (6.9%), dizziness (4.1%), thrombocytopenia (2.9%), and headache (2.7%). 

The suggestion that divalproex (valproate semisodium) causes fewer gastrointestinal adverse reactions than valproate (SEDA-23, 94) (58) has been challenged (74). In other cited studies divalproex was associated with a higher risk of gastrointestinal effects. 

The most commonly observed side effects of valproate are gastrointestinal complaints, tremor, sedation, and weight gain. Gastrointestinal symptoms such as nausea. 

Valproic acid. Although its exact mechanism of action remains uncertain, valproic acid (also valproate sodium, or valproate) may inhibit sodium and/or calcium channel function and perhaps thereby boost GABA inhibitory action as well as reduce glutamate excitatory action (Fig. 7—23). A unique and patented pharmaceutical formulation of valproic acid, called Depakote, reduces gastrointestinal side effects. 

Side effects. Piracetam is well tolerated and there is a low incidence of reported side effects. Those that do occur, at a frequency of less than 10%, include dizziness, insomnia, nausea, gastrointestinal discomfort, weight gain, drowsiness and agitation. Piracetam is indicated only for the treatment of myoclonus, particularly cortical myoclonus. It is used as a second-line drug for patients who are resistant to valproate or the benzodiazepines. 

Side effects. The common dose-related side effects of valproate include nausea, vomiting and gastrointestinal distress weight gain is frequent (estimated as high as 30%) and may be associated with a drug-induced decrease in the beta oxidation of fatty acids. Sedation is also frequent. Alopecia is an unusual side effect of valproate, possibly caused by an abnormal metabolite. Valproate has a number of metabolically linked side... 

Divalproex immediate release formulation reduces gastrointestinal side effects compared to generic valproate... 

Divalproex ER Improves gastrointestinal side effects and alopecia compared to immediate release divalproex or generic valproate... 

Nausea, vomiting, diarrhea, and changes in appetite can occur with all anticonvulsants, although they are usually transient and rarely require withdrawal. Felbamate and to a lesser extent valproate are the anticonvulsants that most often cause gastrointestinal adverse effects. 

Valproic acid is available as sodium, magnesium, and calcium salts, as the free acid, and as a coordination compound, valproate semisodium (divalproex sodium), which comprises the sodium salt of valproic acid and free valproic acid in a 1 1 molar ratio. AH share the same active principle (valproic acid) and have virtually identical tolerability, although the formulation influences the incidence of gastrointestinal adverse effects. Valpromide (rINN) is a prodrug of valproate, to which it is converted with a half-hfe of less than 1 hour. Valnoctamide (rINN) is an isomer of valpromide. 

In a retrospective survey, gastrointestinal adverse effects were less common in 150 patients taking valproate semisodium than in an equal number taking valproic acid (15 versus 29%), despite the fact that serum valproic acid concentrations were comparable in the two groups (73). Patients taking valproate semisodium were less likely to discontinue medication because of gastrointestinal adverse effects (4 versus 13%). The difference was ascribed to the enteric-coated formulation of valproate semisodium. 

The most commonly observed side effects for valproate are gastrointestinal (anorexia, nausea, and Indigestion). These effects can be minimized by selecting divalproex sodium, which is enterically coated, and by Initiating therapy at a low dose. More Importantly, however, valproate is associated with the development of fatal hepatotoxicity, especially in children or when coadministered with other AEDs. Frequent monitoring of liver function tests is mandatory for determining the onset of toxicity. 

Comparative studies In an open prospective comparison of valproate and primidone in 136 patients with partial epilepsy unresponsive to carbamazepine significantly more of those who took valproate (51%) achieved a greater than 50% seizure reduction than those who took primidone (34%) [231 ]. One patient withdrew from valproate because of dizziness and three because of nausea. Of those who took primidone, three withdrew because of dizziness, three patients because of drowsiness, and one because of gastrointestinal complaints. Adverse effects in other patients were mild and gradually disappeared during treatment. 

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