Summary
Levetiracetam 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 2 registered trials linking Levetiracetam to Bipolar Disorder: 2 have completed. The most advanced is Phase 2 (NCT00015769). The largest enrolment is 35 participants (NCT00566150). Registration activity spans 2001 to 2005. The literature layer holds 8 publications for this pair: 2 Cochrane reviews, 1 systematic review and 5 clinical trial publications. Publication years run from 2005 to 2025. 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 | 49.0 (trials 6.0, literature 23.0, tier 15, approved bonus 5.0) |
| Registered trials | 2 total: 0 recruiting, 0 active / not yet recruiting, 2 completed, 0 other |
| Linked publications | 8 (5 clinical trial publications, 2 Cochrane reviews, 1 systematic review) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00015769 | Pilot Study of Levetiracetam (Keppra® (Registered Trademark)) for Bipolar Illness 2001 | completed | Phase 2 | 30 |
| NCT00566150 | Levetiracetam in the Management of Bipolar Depression 2005 | completed | Not applicable | 35 |
Published literature
- Clinical trial publication Investigating the efficacy of levetiracetam as an adjunct to olanzapine for acute manic episodes of bipolar disorder: A double-blind placebo-controlled randomized clinical trialMirzazadeh H, Nourollahi M, Assadian K et al. · Journal of affective disorders · 2025 · PMID 40447146
- Clinical trial publication Levetiracetam as an Adjunctive Treatment for Mania: A Double-Blind, Randomized, Placebo-Controlled TrialKeshavarzi A, Sharifi A, Jahangard L et al. · Neuropsychobiology · 2022 · PMID 34979513
- Clinical trial publication Levetiracetam adjunct to quetiapine for the acute manic phase of bipolar disorder: a randomized, double-blind and placebo-controlled clinical trial of efficacy, safety and tolerabilityZarezadeh F, Arbabi M, Shamabadi A et al. · International clinical psychopharmacology · 2022 · PMID 34864756
- Cochrane review Randomised controlled trials of mood stabilisers for people with autism spectrum disorder: systematic review and meta-analysisLimbu B, Deb S, Roy M et al. · BJPsych open · 2022 · PMID 35197135
- Systematic review Levetiracetam for bipolar disorder: Consideration from a systematic reviewKishi T, Hayakawa H, Kawamoto Y et al. · Bipolar disorders · 2022 · PMID 36064302
- Clinical trial publication Levetiracetam in the management of bipolar depression: a randomized, double-blind, placebo-controlled trialSaricicek A, Maloney K, Muralidharan A et al. · The Journal of clinical psychiatry · 2011 · PMID 21034692
- Cochrane review [Anticonvulsants in the treatment of alcoholism]Bonnet U, Schäfer M, Richter C et al. · Fortschritte der Neurologie-Psychiatrie · 2009 · PMID 19347790
- Clinical trial publication Preliminary observations on the effectiveness of levetiracetam in the open adjunctive treatment of refractory bipolar disorderPost RM, Altshuler LL, Frye MA et al. · The Journal of clinical psychiatry · 2005 · PMID 15766304
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
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 Levetiracetam approved for Bipolar Disorder?
Levetiracetam 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 Levetiracetam in clinical trials for Bipolar Disorder?
ClinicalTrials.gov lists 2 registered trials linking Levetiracetam to Bipolar Disorder: 2 have completed. The most advanced is Phase 2 (NCT00015769). The largest enrolment is 35 participants (NCT00566150). Registration activity spans 2001 to 2005.
What does the evidence show for Levetiracetam in Bipolar Disorder?
Levetiracetam 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.