Side effects of valproate

The most frequent dose-related side effects of valproate are GI complaints, fine hand tremor, and sedation. A /1-blocker may alleviate tremors. Other... 

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

Indigestion, heartburn, and nausea are common side effects of valproate therapy. Use of the divalproex sodium preparation will help mitigate these effects. Patients may also be encouraged to take their doses with food. The symptomatic use of histamine H2 blockers, such as famotidine, is sometimes warranted. In most cases, however, dyspepsia is transient and not severe. Pancreatitis is a rare occurrence in patients receiving relatively high doses of valproate. If vomiting and severe abdominal pain develop during valproate therapy, serum amylase levels should be determined immediately. 

Weight gain is a common side effect of valproate treatment. Isojarvi et al. (1996) reported significant weight gain with associated hyper-insulinemia in approximately 50% of a cohort of women taking valproate. This side effect does not appear to be dose dependent. Diet and exercise should be recommended early in treatment. 

One of the most common side effects of valproate therapy is benign essential tremor. Drowsiness is another common side effect, but tolerance often develops once a steady-state level of the drug is... 

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... 

Some of the side effects of valproate administration to young children to control seizures (ketosis and liver damage) are associated with sequestration of CoA as valproyl CoA, which is poorly metabolized, and the administration of pantothenate supplements (generally together with carnitine Section 14.1) prevents depletion of CoA and reduces the risk of liver damage (Thurston and Hauhart, 1992). In the same way, pantothenate supplements protect mice against neural tube defects caused by valproate (Sato et al., 1995). 

Side effects of valproate are few. It causes thinning and curling of the hair in about 10% of patients. It is potentially hepatotoxic but this is rare. Valproate has been linked with increased risk of neural tube defects in the unborn child. Folic acid supplements are recommended as a precaution. 

The main adverse side-effects of valproate are headaches, tremor, weight gain, sedation, decreased liver function tests, decreased platelet count, and mild leukocytosis. 

Carbamazepine is also most beneficial for patients with mixed episodes and rapid cycling. However, many patients find the side effects of carbamazepine more troublesome than those of valproate, and becanse carbamazepine has a penchant for nntoward drug-drug interactions, we reserve the use of carbamazepine for those patients who are unable to tolerate valproate, lithium, and the atypical antipsychotic... 

Another serious side effect of clozapine is a risk of seizures. This mainly occurs at higher doses of the drug, and having a seizure is not necessarily a sufficient reason to stop clozapine permanently. If the clozapine has been especially helpful, an anticonvulsant can be added to protect against further seizures. Valproate (Depakote) may be best in this regard because it not only provides protection from seizures but also may help to relieve some of the symptoms of schizophrenia. Recently, it has become clear that two atypical antipsychotic drugs, clozapine and olanzapine, are associated with an increased risk for the development of type II diabetes. 

Herranz, J.L., Armijo, J.A., and Arteaga, R. (1988) Clinical side effects of phenobarbital, primidone, phenytoin, carbamazepine, and valproate during monotherapy in children. Epilepsia 29 794-804. 

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. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

As with carbamazepine, the historical use of valproate for anxiety is not supported by robust clinical trials. A randomised study showed efficacy in panic disorder (Lum et al. 1991) and benefit has been reported in open studies in OCD and PTSD. The major side-effects are tremor, nausea, ataxia and weight gain and there is the potential for drug interactions via inhibition of hepatic enzymes. 

In the absence of sound research on antimanic medicines in young people with MR, clinicians treating such patients have no choice but to extrapolate from the available work with typically developing children and with adults having MR. Given lithium s side effect profile and narrow therapeutic index, it may be wise to give valproate and/or carbamazepine a trial before resorting to lithium. 

At the borderline between semisynthesis and patterned synthesis, versatile total syntheses may provide access to diversified bioactive structures. Classically, analogues of the active drug are sought that avoid the resistance developed by pathogens and show reduced side effects. In lucky cases, chemical simplification has afforded the wonder drug. This is the case of sodium valproate (2-propylvaleric acid sodium salt), which was synthesized in the fall of the XIX century and nearly a hundred years later became a leading drug in the treatment of epilepsy. 

COMPARISON OF LITHIUM AND VALPROATE SIDE-EFFECT PROFILES... 

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