Summary
Divalproex Sodium has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Bipolar Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Bipolar Disorder. ClinicalTrials.gov lists 8 registered trials linking Divalproex Sodium to Bipolar Disorder: 5 have completed; 3 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00667745). The largest enrolment is 1000 participants (NCT00451542). Registration activity spans 2003 to 2011. The literature layer holds 7 publications for this pair: 1 Cochrane review, 1 randomised controlled trial publication and 5 clinical trial publications. Publication years run from 2006 to 2022. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Bipolar Disorder ranks 389 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Natural episodic pattern: untreated, median episode length 3-6 months; recurrence in 90% within 5 years; functional impairment between episodes in 30-60%; suicide risk 20-30x general population.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 63.0 (trials 25.0, literature 18.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 5 completed, 3 other |
| Linked publications | 7 (5 clinical trial publications, 1 Cochrane review, 1 randomised controlled trial publication) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | inhibitor |
| Data sources | DGIdb |
| Linked via biomarker / target | ALDH5A1 |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT00667745 | Effectiveness of Lithium Plus Optimized Medication in Treating People With Bipolar Disorder 2008 | completed | Phase 4 | 283 |
| NCT00203528 | Divalproex ER vs. Risperidone for Bipolar Disorder With Comorbid Substance Use Disorder 2004 | completed | Phase 4 | 30 |
| NCT01588457 | Sequential Multiple Assignment Treatment for Bipolar Disorder 2011 | completed | Phase 4 | 112 |
| NCT00139074 | Seroquel in Acute Mania: Study to Investigate if Valproate Add-On Therapy is Superior to Quetiapine Monotherapy in Acutely Manic Patients 2005 | terminated | Phase 4 | 17 |
| NCT00332098 | Effectiveness of Family-Focused Treatment Plus Pharmacotherapy for Bipolar Disorder in Adolescents 2006 | completed | Phase 3 | 145 |
| NCT00204503 | Open-Label Depakote ER in Patients With Bipolar I or II Depression and Alcohol Abuse or Dependence 2003 | withdrawn | Phase 2 | — |
| NCT00240110 | Valproate Efficacy in Cocaine-Bipolar Comorbidity 2006 | completed | PHASE1, PHASE2 | 152 |
| NCT00451542 | Divalproex vs. Lamotrigine for Bipolar Disorder 2006 | terminated | Not applicable | 1,000 |
Published literature
- Clinical trial publication Fixed Dose Combination Tablets of Aripiprazole and Divalproex Sodium: a Pilot Pharmacokinetic Study in Human VolunteersAhmed Z, Subhan F, Ahmed S · AAPS PharmSciTech · 2022 · PMID 35986197
- Clinical trial publication Depression and Suicidality Outcomes in the Treatment of Early Age Mania StudySalpekar JA, Joshi PT, Axelson DA et al. · Journal of the American Academy of Child and Adolescent Psychiatry · 2015 · PMID 26598475
- Clinical trial publication Risperidone and divalproex differentially engage the fronto-striato-temporal circuitry in pediatric mania: a pharmacological functional magnetic resonance imaging studyPavuluri MN, Passarotti AM, Fitzgerald JM et al. · Journal of the American Academy of Child and Adolescent Psychiatry · 2012 · PMID 22265362
- Clinical trial publication A pilot pharmacotherapy trial for depressed youths at high genetic risk for bipolarityFindling RL, Lingler J, Rowles BM et al. · Journal of child and adolescent psychopharmacology · 2008 · PMID 19108666
- Clinical trial publication Open-label steady-state pharmacokinetic drug interaction study on co-administered quetiapine fumarate and divalproex sodium in patients with schizophrenia, schizoaffective disorder, or bipolar disorderWinter HR, DeVane CL, Figueroa C et al. · Human psychopharmacology · 2007 · PMID 17729385
- Randomized controlled trial Double-blind, placebo-controlled trial of divalproex monotherapy in the treatment of symptomatic youth at high risk for developing bipolar disorderFindling RL, Frazier TW, Youngstrom EA et al. · The Journal of clinical psychiatry · 2007 · PMID 17503990
- Cochrane review Treatments for late-life bipolar disorderAziz R, Lorberg B, Tampi RR · The American journal of geriatric pharmacotherapy · 2006 · PMID 17296540
Mechanism and notes
Recorded mechanism or class: inhibitor.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ALDH5A1. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Divalproex Sodium approved for Bipolar Disorder?
Divalproex Sodium has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Bipolar Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Bipolar Disorder. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Divalproex Sodium in clinical trials for Bipolar Disorder?
ClinicalTrials.gov lists 8 registered trials linking Divalproex Sodium to Bipolar Disorder: 5 have completed; 3 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00667745). The largest enrolment is 1000 participants (NCT00451542). Registration activity spans 2003 to 2011.
What does the evidence show for Divalproex Sodium in Bipolar Disorder?
Divalproex Sodium has both completed registered trials and synthesis-level publications linked to Bipolar Disorder. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ALDH5A1. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.