Valproic acid side effects

The traditional treatment of tonic-clonic seizures is phenytoin or phe-nobarbital, but the use of carbamazepine and valproic acid is increasing, as efficacy is equal and side effects are more favorable. 

Studies suggest that as monotherapy for partial seizures, lamotrigine is as effective as carbamazepine and phenytoin lamotrigine may be better tolerated. Clinical data suggest that oxcarbazepine is as effective as phenytoin, valproic acid, and immediate-release carbamazepine, with perhaps fewer side effects. 

The most frequent side effects are diplopia, drowsiness, ataxia, and headache. Rashes are usually mild to moderate, but Stevens-Johnson reaction has also occurred. The incidence of the more serious rashes appears to be increased in patients who are also receiving valproic acid and who have rapid dosage titration. Valproic acid substantially inhibits the metabolism of lamotrigine. 

The enteric-coated tablet divalproex sodium causes fewer GI side effects. It is metabolized in the gut to valproic acid. When switching from Depakote to Depakote-ER, the dose should be increased by 14% to 20%. Depakote ER may be given once daily. 

Side effects of valproic acid and divalproex sodium include nausea (less common with divalproex sodium and gradual dosing titration), tremor,... 

Anticonvulsants. Scattered case reports suggest that carbamazepine (Tegretol) and valproic acid (Depakote, Depakene) may be helpful in the treatment of panic disorder. This has yet to be verified in systematic studies. Furthermore, because these anticonvulsants are hindered by toxicity and side effect concerns (cf. Chapter 3), they should only be considered if other better studied and more tolerable treatment options have failed. 

Donovan et al. (1996, 1997) completed an open study evaluating the use of valproic acid (Depakote) in adolescent outpatients with marijuana abuse or dependence and explosive mood disorder (mood symptoms were not classified using the DSM FV Diagnostic System). Eight subjects were prescribed 1000 mg of valproic acid (Depakote) for 5 weeks, in addition to regular therapy sessions, but did not receive any other psychotropic medications. All subjects showed a significant improvement in their marijuana use (p <0.007) and their affective symptoms (p < 0.001), although both outcomes were measured only by self-report. The most common adverse events were nausea and sedation. No subjects discontinued because of these side effects, nor were there any reported interactions between the valproic acid (Depakote) and substances of abuse. 

Hurd RW, Van Rinsvelt HA, Wilder BJ, et al Selenium, zinc, and copper changes with valproic acid possible relation to drug side effects. Neurology 34 1393-1395, 1984... 

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. 

Valproic acid can have unacceptable side effects, such as hair loss, weight gain, and sedation. Certain problems can limit valproic acid s usefulness in women of child-bearing potential, including the fact that it can cause neural tube defects in... 

Carbamazepine. The anticonvulsant carbamazepine was actually the first to be shown to be effective in the manic phase of bipolar disorder, but it has not been approved for this use by regulatory authorities such as the U.S. Food and Drug Administration (FDA). Its mechanism of action may be to enhance GABA function, perhaps in part by actions on sodium and/or potassium channels (Fig. 7—24). Because its efficacy is less well documented and its side effects can include sedation and hematological abnormalities, it is not as well accepted for first-line use in the treatment of mood disorders as either lithium or valproic acid. 

Levine J, Chengappa KN, ParepaUy H. Side effect profile of enteric-coated divalproex sodium versus valproic acid. J Clin Psychiatry 2000 61(9) 680-1. 

Valproic acid is tolerated slightly better than carbamazepine relative to nervous system side effects, notably in fewer complaints of fatigue and dizziness. Gastrointestinal side effects of nausea, vomiting, and indigestion, are common, although these are usually transient. Use of sustained-release tablets (Depakote) may reduce these effects. Valproic acid can occasionally interfere with the normal blood clotting cycle. 

Monitor children for appearance of (or worsening of) cognitive and behavioral side effects associated with anticonvulsants. With caramazepine these can include insomnia, irritability, emotional lability, and impaired task performance. With valproic acid observe for excessive drowsiness and (minimal) effect on task performance. 

The traditional treatment of tonic-clonic seizures is phenytoin or phenobarbital however, the use of carbamazepine and valproic acid is increasing because these AEDs have a lower incidence of side effects and equal efficacy. Valproic acid generally is considered the drug of first choice for atonic seizures and for juvenile myoclonic epilepsy. Lamotrigine and perhaps topiramate and zonisamide may be alternative agents for these seizure types. 

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