valproate (divalproex)

Mood stabilizer • Brands: DEPAKOTE

Last reviewed: 2026-03-31

General information

Class: Mood stabilizer
Common US brands: DEPAKOTE
Typical dose range: Acute mania: initiate 750–1,000 mg/day (divided TID for DR or once daily ER) and titrate to serum 50–125 µg/mL; loading up to 20–30 mg/kg/day can achieve rapid control.
Therapeutic drug monitoring recommended; reference range 50–125 µg/mL.
Last reviewed: 2026-03-31

Dosing & forms

Forms/strengths: Divalproex sodium delayed-release tablets: 125 mg, 250 mg, 500 mg.; Divalproex sodium extended-release tablets: 250 mg, 500 mg.; Valproic acid capsules 250 mg, oral solution 250 mg/5 mL, sprinkle capsules 125 mg.
Frequency: Acute mania: initiate 750–1,000 mg/day (divided TID for DR or once daily ER) and titrate to serum 50–125 µg/mL; loading up to 20–30 mg/kg/day can achieve rapid control.
Typical range: Acute mania: initiate 750–1,000 mg/day (divided TID for DR or once daily ER) and titrate to serum 50–125 µg/mL; loading up to 20–30 mg/kg/day can achieve rapid control.
Therapeutic range: 50–125 µg/mL

Mechanism (brief)

Increases GABA; modulates voltage-gated sodium and calcium channels.

Metabolism & Half‑life

Metabolism: UGT, beta-oxidation
Half‑life: Steady-state mean 12 h

Therapeutic Drug Monitoring (TDM)

Recommended: Yes

Reference range: 50–125 µg/mL

Sampling: Trough (3–5 days after dose change)

View labelExact

Monitoring highlights

Baseline: LFTs, CBC with platelets, pregnancy test if relevant, weight/BMI.
Level timing: 12-hour trough (extended-release may differ); target 50–125 µg/mL based on clinical context.
Ongoing: Periodic LFTs and CBC; monitor metabolic effects and sedation.
Precautions: Reinforce teratogenicity counseling; review pancreatitis and hepatotoxicity warnings.
Drug interactions: Adjust for enzyme induction (UGT), lamotrigine titration, and other interacting therapies.

Sources

DEPAKOTE (divalproex sodium) prescribing information — DailyMed (2025)
AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)
CANMAT/ISBD guidance on valproate for bipolar disorder — Bipolar Disorders (2021)
Bipolar disorder: assessment and management (NICE guideline CG185) — National Institute for Health and Care Excellence (2020)
Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis — Journal of Affective Disorders (2010)

General information

Class: Mood stabilizer

Common US brands: DEPAKOTE

Typical dose range: Acute mania: initiate 750–1,000 mg/day (divided TID for DR or once daily ER) and titrate to serum 50–125 µg/mL; loading up to 20–30 mg/kg/day can achieve rapid control.

Therapeutic drug monitoring recommended; reference range 50–125 µg/mL.

Last reviewed: 2026-03-31

Dosing & forms

Forms/strengths: Divalproex sodium delayed-release tablets: 125 mg, 250 mg, 500 mg.; Divalproex sodium extended-release tablets: 250 mg, 500 mg.; Valproic acid capsules 250 mg, oral solution 250 mg/5 mL, sprinkle capsules 125 mg.

Frequency: Acute mania: initiate 750–1,000 mg/day (divided TID for DR or once daily ER) and titrate to serum 50–125 µg/mL; loading up to 20–30 mg/kg/day can achieve rapid control.

Typical range: Acute mania: initiate 750–1,000 mg/day (divided TID for DR or once daily ER) and titrate to serum 50–125 µg/mL; loading up to 20–30 mg/kg/day can achieve rapid control.

Therapeutic range: 50–125 µg/mL

Monitoring highlights

Baseline: LFTs, CBC with platelets, pregnancy test if relevant, weight/BMI.

Level timing: 12-hour trough (extended-release may differ); target 50–125 µg/mL based on clinical context.

Ongoing: Periodic LFTs and CBC; monitor metabolic effects and sedation.

Precautions: Reinforce teratogenicity counseling; review pancreatitis and hepatotoxicity warnings.

Drug interactions: Adjust for enzyme induction (UGT), lamotrigine titration, and other interacting therapies.