Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE):…
If we're choosing between lithium and valproate for long-term prevention, what makes one the better fit for me?
Well-supported by good-quality research. how we score evidence
Caveat on this rating: Open-label design and part-funded by Sanofi-Aventis (a valproate manufacturer), though the results favored lithium over valproate.
In 330 people with bipolar I disorder followed for up to two years, lithium alone or lithium plus valproate prevented relapse better than valproate alone (54% of the combination group vs 69% of the valproate group needed a new intervention for a mood episode); adding valproate to lithium gave no clear extra benefit over lithium alone.
Worth asking
If we're choosing between lithium and valproate for long-term prevention, what makes one the better fit for me?
What it is FDA approved for
Read off the label. Trial duration and approval year are shown only where they were recorded — never inferred.
- Treatment of manic episodes of bipolar disorder
- Maintenance treatment of bipolar disorder
Source
Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial — Geddes JR, et al. (BALANCE investigators and collaborators) (2010)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1016/S0140-6736(09)61828-6
DOI: 10.1016/S0140-6736(09)61828-6
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Mixed public and industry funding
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 330
- Preregistered
- Yes
- Conflicts disclosed
- No
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "strong evidence". Well-supported by good-quality research. It scores 72 out of 100 on our published rubric. One caveat travels with that badge: Open-label design and part-funded by Sanofi-Aventis (a valproate manufacturer), though the results favored lithium over valproate. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial — Geddes JR, et al. (BALANCE investigators and collaborators) (2010). Published in: Top-tier peer-reviewed journal. DOI: 10.1016/S0140-6736(09)61828-6. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Randomised controlled trial. Funding: Mixed public and industry funding. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is lithium (Lithobid, Eskalith), lithobid, eskalith FDA approved?
Yes — FDA approved for Treatment of manic episodes of bipolar disorder, Maintenance treatment of bipolar disorder. Approval is for a specific indication, not for everything the drug is prescribed for.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.