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Table Reference Number

Note. CNS = central nervous system; ER = extended-release; FDA = U.S. Food and Drug Administration; GI = gastrointestinal; IR = immediate-release.

Valproate therapy: overview

Efficacy

Acute mania (FDA approved)

Bipolar prophylaxis (may be effective)

Mixed, rapid-cycling bipolar

Seizure disorders (FDA approved)

Side effects

Weight gain

Sedation

GI upset

Safety in overdose

Serious effects notable mostly at 20 times normal serum level. Symptoms include nausea, vomiting, CNS depression, and seizures. Manage with gastric lavage, forced emesis, and assisted ventilation.

Dosage and administration

Start IR formulation at 15 mg/kg/day and ER formulation at 25 mg/kg/day in divided doses, up to a maximum of 60 mg/kg. Achieve serum levels of 50–100 g/mL.

Discontinuation

Rapid discontinuation increases the risk of rapid relapse in bipolar disorder. Otherwise, discontinuation symptoms are uncommon.

Drug interactions

Drugs that valproate serum levels include:

 cimetidine

 erythromycin

 phenothiazines

 fluoxetine

 aspirin

 ibuprofen

Drugs that valproate serum levels include:

 rifampin

 carbamazepine

 phenobarbital

 ethosuximide

Table Reference Number
Table 5–4. Drug interactions of anticonvulsant mood stabilizers

References

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