Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial.
Bipolar Affective disorder: Lithium/ANtiConvulsant Evaluation (BALANCE), was a randomized, open-label trial comparing lithium, valproate, and their combination, in the prevention of relapse in bipolar I disorder. Combination of lithium plus valproate was significantly more likely to prevent relapse than valproate alone. Lithium was slightly more effective at preventing relapse than valproate.
- N=330 patients, ages ≥16, with bipolar I disorder were randomized (open-label) to one of three arms (no placebo group):
- Lithium (n=110)
- Valproate (n=110)
- Lithium plus Valproate (n=110)
- All patients took both drugs during an initial run-in phase (4-8 weeks) to ensure patients could tolerate both drugs prior to randomization.
- Up to 24 month follow-up.
- Setting: 41 sites in UK, France, USA, Italy, 2001-2007.
- Primary outcome: intervention for an emergent mood episode (includes drug treatment, hospitalization).
- For long-term treatment of bipolar I, lithium monotherapy and lithium plus valproate were both more likely to prevent relapse compared with valproate monotherapy.
- Primary outcome (intervention for emergent mood episode) occurred in:
- 54% of the combination group
- 59% of the lithium group
- 69% of the valproate group
- Hazard ratios of the primary outcome (95% CI, P-value):
- Combo vs. valproate: 0.59 (0.42-0.83, P=0.0023)
- Combo vs. lithium: 0.82 (0.58-1.17 P=0.27)
- Lithium vs. valproate: 0.71 (0.51-1.00, P=0.0472)
BALANCE investigators and collaborators, Geddes JR, Goodwin GM, et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet. 2010;375(9712):385–395. doi:10.1016/S0140-6736(09)61828-6.