Summary
Valproate 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lists 8 registered trials linking Valproate Sodium to Bipolar Disorder: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00477373). The largest enrolment is 3416 participants (NCT01064297). Registration activity spans 2001 to 2007. The literature layer holds 4 publications for this pair: 2 systematic reviews and 2 clinical trial publications. Publication years run from 2003 to 2019. 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 | 55.0 (trials 25.0, literature 10.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 6 completed, 2 other |
| Linked publications | 4 (2 systematic reviews, 2 clinical trial publications) |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00203528 | Divalproex ER vs. Risperidone for Bipolar Disorder With Comorbid Substance Use Disorder 2004 | completed | Phase 4 | 30 |
| NCT00477373 | Gulf Evaluation of VAlproate (Depakine Chrono) in maNia Study 2006 | completed | Phase 4 | 70 |
| 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 | — |
| NCT00562861 | Treatment for Bipolar Depression: Acute & Prophylactic Efficacy With Citalopram 2007 | completed | PHASE2, PHASE3 | 119 |
| NCT01064297 | Lamotrigine Pregnancy Registry (LAM05) 2001 | completed | Not applicable | 3,416 |
| NCT00240110 | Valproate Efficacy in Cocaine-Bipolar Comorbidity 2006 | completed | PHASE1, PHASE2 | 152 |
Published literature
- Systematic review Pharmacotherapies for co-occurring substance use and bipolar disorders: A systematic reviewColes AS, Sasiadek J, George TP · Bipolar disorders · 2019 · PMID 31077521
- Systematic review Risks of neurobehavioral teratogenicity associated with prenatal exposure to valproate monotherapy: a systematic review with regulatory repercussionsGentile S · CNS spectrums · 2014 · PMID 24571806
- Clinical trial publication [Open randomized comparative twelve-week study of lithium and valproate in manic episode]Mosolov SN, Kostiukova EG, Kapiletti SG et al. · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2009 · PMID 20032954
- Clinical trial publication Valproate, bipolar disorder and polycystic ovarian syndromeMcIntyre RS, Mancini DA, McCann S et al. · Bipolar disorders · 2003 · PMID 12656935
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 Valproate Sodium approved for Bipolar Disorder?
Valproate 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 Valproate Sodium in clinical trials for Bipolar Disorder?
ClinicalTrials.gov lists 8 registered trials linking Valproate Sodium to Bipolar Disorder: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00477373). The largest enrolment is 3416 participants (NCT01064297). Registration activity spans 2001 to 2007.
What does the evidence show for Valproate Sodium in Bipolar Disorder?
Valproate 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.