Preventing Bipolar I Relapse: Results of the BALANCE Trial

Preventing Bipolar I Relapse: Results of the BALANCE Trial

Relapse rates were high overall, but better with lithium–valproate combination or lithium monotherapy than with valproate monotherapy.

Most treatment guidelines for bipolar disorder list lithium and valproate as first-line mood stabilizers, although lithium prescriptions have declined recently. In a randomized, open-label, multisite, international, 2-year trial, researchers compared the effectiveness of lithium, valproate, and their combination in preventing relapse.

First, 459 nonacutely ill patients with bipolar I disorder (74% without history of mood-stabilizer maintenance) received the combination at minimally effective doses (typically, for 4–8 weeks). The 330 participants who tolerated combination treatment were then randomized to continue the combination or to receive either monotherapy (the other drug was gradually withdrawn). Treatment groups were balanced for multiple illness characteristics.

Drug adherence was good, and follow-up covered 589.8 person-years. Relapse, defined as intervention for a new mood episode, occurred in 54% of combination-treatment recipients, 59% of lithium recipients, and 69% of valproate recipients. Combination treatment and lithium were statistically similar to each other in efficacy and superior to valproate. Combination therapy appeared most effective in preventing manic episodes and lithium in preventing depressive episodes. Results were not affected by baseline severity, polarity of the most recent episode, drug doses, blood levels, or when events in the first 3 months were excluded.

Comment: This study suggests that the most effective agents for preventing relapse are lithium–valproate combination and lithium monotherapy (numbers needed to treat, 7 and 10, compared with valproate alone). However, the high relapse rates suggest a serious need for new treatments.

Study limitations include the open treatment allocation, and the absence of both a placebo group and a systematic assessment of symptoms. Its strengths are its real-world design, diverse patient population, presence of a clinical endpoint (i.e., need for treatment change), and enrollment of patients who tolerated both drugs (in contrast to some previous studies).

Lithium is often underused. Its use may have declined because of clinicians' concerns about thyroid and renal effects, their reluctance to do the necessary monitoring, or the vigorous marketing of valproate. These results clarify that more patients should be given lithium, probably alone initially and then in combination with valproate.

— Peter Roy-Byrne, MD

Published in Journal Watch Psychiatry January 11, 2010

Citation(s):

Geddes JR et al. for the BALANCE Investigators and Collaborators. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): A randomised open-label trial. Lancet 2009 Dec 23; [e-pub ahead of print]. (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961828-6/fulltext)

http://psychiatry.jwatch.org/cgi/content/full/2010/111/1