What is the recommended dosage of Depakote (valproate) for bipolar disorder type 2?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: October 1, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Depakote (Divalproex Sodium) Dosage for Bipolar Disorder Type 2

For bipolar disorder type 2, divalproex sodium (Depakote) should be initiated at 125 mg twice daily and titrated to a therapeutic blood level of 40-90 mcg/mL, which typically requires doses between 125-500 mg daily for cyclothymia/bipolar II patients.1, 2

Initial Dosing and Titration

  • Starting dose: 125 mg twice daily 1
  • Titration: Increase dose gradually based on clinical response and side effects
  • Target blood level: 40-90 mcg/mL 1
  • Dosing schedule: Can be given as divided doses or once-daily dosing (especially with extended-release formulation) 3

Dosing Considerations Based on Severity

Research indicates that bipolar II patients may respond to lower doses than those typically used for bipolar I disorder:

  • Mild to moderate bipolar II: 125-500 mg daily (mean 351 mg) corresponding to lower serum levels (mean 32.5 mcg/mL) 2
  • More severe symptoms: May require higher doses within the therapeutic range 2
  • Maintenance treatment: Should be continued for at least 2 years after the last episode 4

Monitoring Parameters

Regular monitoring is essential when using divalproex:

  • Blood levels: Check serum valproate levels regularly to ensure therapeutic range (40-90 mcg/mL)
  • Liver function: Monitor liver enzymes regularly 1
  • Hematologic monitoring: Check platelets, prothrombin time, and partial thromboplastin time 1
  • Weight and metabolic parameters: Monitor weight, BMI, blood pressure, glucose, and lipids 4

Special Considerations

  • Depressive episodes: Divalproex has shown efficacy in bipolar II depression, with studies showing response rates of 63% overall (82% in medication-naïve patients) 3, 5
  • Combination therapy: For depressive episodes, may need to be combined with an antidepressant (preferably an SSRI like fluoxetine) 1, 4
  • Extended-release formulation: Consider for improved adherence and tolerability with once-daily dosing 6

Common Pitfalls and Caveats

  • Avoid underdosing: Ensure blood levels reach therapeutic range for optimal efficacy
  • Avoid rapid titration: Gradual dose increases minimize side effects
  • Monitor for side effects: Weight gain, sedation, tremor, gastrointestinal disturbances
  • Pregnancy considerations: Divalproex has teratogenic potential and should be used with caution in women of childbearing age
  • Medication interactions: Be aware of potential interactions with other medications that may affect valproate levels

Divalproex is generally better tolerated than other mood stabilizers like carbamazepine, making it a preferred option for many patients with bipolar II disorder 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Medication Management and Side Effects

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Divalproex sodium in the treatment of adults with bipolar disorder.

Expert review of neurotherapeutics, 2004

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.