TaperCommunityvalproate / divalproex
Boxed Warning
Hepatotoxicity (especially in children under 2), severe teratogenicity (neural tube defects, decreased IQ), and pancreatitis.
Valproate (divalproex sodium) is an anticonvulsant used for bipolar disorder (especially mania), epilepsy, and migraine prevention. Carries a black-box warning for hepatotoxicity, pancreatitis, and severe teratogenicity.
125mg, 250mg, 500mg DR; 250mg, 500mg ER; sprinkle capsules 125mg
Tablets DR: 125mg, 250mg, 500mg; Tablets ER: 250mg, 500mg; Capsules (sprinkle): 125mg; Oral solution: 250mg/5mL
Category X (mood/migraine indications); Category D (epilepsy)
Increases GABA, blocks voltage-gated sodium channels, modulates T-type calcium channels. Multiple mechanisms with no single dominant target.
Slow taper over weeks. In bipolar disorder, plan continuity of mood coverage.
Valproate withdrawal in mood disorders carries relapse risk. Slow taper with mood monitoring; consider cross-titration to alternative stabilizer where appropriate.
3-7 days after stopping
1-3 weeks
4-8 weeks for most non-seizure symptoms
Mood instability can persist months without an alternative stabilizer
Toxicity
Hepatotoxicity, pancreatitis, hyperammonemic encephalopathy, thrombocytopenia, pancytopenia, weight gain, hair loss, tremor, PCOS-like features in women, neural tube defects in pregnancy.
Pharmacokinetics
Hepatic via beta-oxidation, glucuronidation, CYP2C9, CYP2C19.
~90%
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