valproate (divalproex)

Mood stabilizer

Brands: DEPAKOTE

Last reviewed 2025-09-23

Reviewed by PsychMed Editorial Team.

View details

Quick answers

What is valproate (divalproex)?
Valproate (divalproex sodium/valproic acid) is a broad-spectrum mood stabilizer effective for acute mania and maintenance in bipolar disorder, also widely used in neurology indications.
What is DEPAKOTE?
DEPAKOTE is a brand name for valproate (divalproex).
What is DEPAKOTE (valproate (divalproex)) used for?
Label indications include: Acute mania associated with bipolar disorder; seizures (various types).
What drug class is DEPAKOTE (valproate (divalproex))?
Mood stabilizer.
What is the mechanism of action of DEPAKOTE (valproate (divalproex))?
Increases GABA; modulates voltage-gated sodium and calcium channels.
What strengths does DEPAKOTE (valproate (divalproex)) come in?
Divalproex sodium delayed-release tablets: 125 mg, 250 mg, 500 mg.
Is DEPAKOTE (valproate (divalproex)) a controlled substance?
No — it is not scheduled as a controlled substance under U.S. federal law.
How is valproate (divalproex) started as a long-acting injectable (LAI)?
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.

Snapshot

Class: Mood stabilizer
Common US brands: DEPAKOTE
Therapeutic drug monitoring recommended; reference range 50000–125000 ng/mL.
Last reviewed: 2025-09-23

Label indications

Acute mania associated with bipolar disorder; seizures (various types).

View labelExact

Clinical Highlights

Valproate (divalproex sodium/valproic acid) is a broad-spectrum mood stabilizer effective for acute mania and maintenance in bipolar disorder, also widely used in neurology indications. This profile concentrates on bipolar disorder management, emphasizing hepatotoxicity, teratogenicity, and metabolic monitoring.

The compare view and the valproate evidence feed can help contrast metabolic effects, serum monitoring, and teratogenic risk before altering maintenance regimens.
Favored for rapid control of mixed states and rapid cycling; clinicians vigilantly monitor liver function, weight, and teratogenic risks and counsel on contraception.
Acute mania (bipolar disorder) (FDA 1995)
Maintenance: widely used but off-label (no FDA approval for maintenance)
Generic: All formulations are available generically.

Dosing & Formulations

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.
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.
Maintenance: adjust to maintain serum 50–100 µg/mL (some target 80–120 µg/mL for relapse prevention).
Extended-release doses may need to be 8–20% higher than delayed-release to achieve equivalent exposure.

Monitoring & Risks

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.
Boxed warning: Hepatotoxicity (especially in young children or patients with mitochondrial disorders).

Drug Interactions

Enzyme-inducing antiepileptics (carbamazepine, phenytoin, phenobarbital) lower valproate levels; adjust dosing. Valproate increases lamotrigine levels significantly—reduce lamotrigine dose by 50–75%.

Aspirin and warfarin displace valproate from proteins—monitor bleeding parameters.
Topiramate increases hyperammonemia risk; monitor ammonia and mental status.
Carbapenem antibiotics markedly reduce valproate levels—avoid combination.

Practice Notes

Provide thorough contraception counseling and document risk discussions for patients capable of pregnancy; consider folic acid supplementation. Encourage lifestyle modifications (diet, exercise) to mitigate weight gain and metabolic effects; monitor BMI, lipids, glucose similar to SGAs.

Educate about signs of hepatic dysfunction, pancreatitis, and hyperammonemia requiring urgent evaluation.
Extended-release formulations improve adherence and GI tolerability; maintain consistent formulation for level interpretation.
Taper gradually when discontinuing to avoid relapse or seizure risk, and coordinate relapse-prevention plans through the bipolar disorder hub when switching regimens.
Document follow-up cadence and relapse warning signs early, especially during acute titration and after any formulation changes.

References

DEPAKOTE (divalproex sodium) prescribing information — DailyMed (2025)
CANMAT/ISBD guidance on valproate for bipolar disorder — Bipolar Disorders (2021)
Valproate FOR THE Treatment OF Acute Bipolar Depression: Systematic Review AND Meta Analysis — Journal of Affective Disorders (2010)
FDA safety communication: valproate contraindicated in pregnancy for migraine prophylaxis — U.S. Food and Drug Administration (2013)