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Depakote Fact Sheet

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Medication Name (brand): 
Depakote
Medication Name (clinical): 
valproic acid
Manufacturer: 

Abbott, market exclusivity expires 2008; Depakene is available as a generic

Indications: 

  • Acute Mania (only Depakote ER is officially approved for this)

  • Off-Label use for Prevention of Depression and Mania in Bipolar Disorder
  • Off-label use for treating various problems related to impulsivity and rage

Mechanism: 

Unknown, may work by increasing GABA (gamma-aminobutyric acid)

Dosing: 

  • Most clinicians dose Depakote at bedtime in order to increase compliance and minimize side effects, regardless of the formulation used.

  • Start at 250-500 mg QHS, gradually increasing to achieve a blood Depakote level of 70-80 mcg/mL, which will often be in the 1000-1250 mg QHS range.
  • When converting from regular Depakote to Depakote ER, be aware that patients will see about 20% less valproic acid with the ER formulation, making converting somewhat tricky, given that Depakote ER only comes in the 500 mg option.
  • The dose of Depakote should be decreased in both liver disease and renal impairment.

Side Effects: 

  • Most common: nausea (switch to Depakote ER or Depakote sprinkles), fatigue, dizziness, tremor (treat with Inderal LA 60 mg QAM or regular Inderal 20 mg BID-TID)

  • Thrombocytopenia (slight lowering of platelets not uncommon; significant problems more likely in elderly)
  • Elevated liver function tests (not uncommon, usually benign, but need to monitor for very rare hepatic failure)
  • Polycystic ovarian syndrome (PCOS) in about 10% of women (irregular periods, hirsutism, elevated testosterone)
  • Black box warnings: Hepatotoxicity (rare, more likely to occur in young children), pancreatitis (also quite rare).
  • Pregnancy Category D (high rate of neural tube defects)

Drug-drug Interactions: 

Increases Lamictal levels; aspirin increases Depakote levels; combination with topiramate can lead to encephalopathy

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