Lithium plus valproate versus monotherapy for relapse prevention in bipolar I disorder

January 01, 0001

Lithium plus valproate versus monotherapy for relapse prevention in bipolar I disorder

Lithium carbonate and valproate semisodium are both recommended as monotherapy for prevention of relapse in bipolar disorder, but are not individually fully effective in many patients. The researchers from multiple countries aimed to establish whether lithium plus valproate was better than monotherapy with either drug alone for relapse prevention in bipolar I disorder. They enrolled 330 patients aged 16 years and older with bipolar I disorder and randomly allocated them to open-label lithium monotherapy (plasma concentration 0.4-1.0 mmol per L, n=110), valproate monotherapy (750-1250 mg, n=110), or both agents in combination (n=110), after an active run-in of 4-8 weeks on the combination. Outcome events were assessed by the trial management team, who were masked to treatment assignment. Participants were followed up for up to 24 months.

59 (54%) of 110 people in the combination therapy group, 65 (59%) of 110 in the lithium group, and 76 (69%) of 110 in the valproate group had a primary outcome event during follow-up. Hazard ratios for the primary outcome were 0.59 (significant) for combination therapy versus valproate, 0.82 (not significant) for combination therapy versus lithium, and 0.71 (significant) for lithium versus valproate. 16 participants had serious adverse events after randomization, seven receiving valproate monotherapy (three deaths), five lithium monotherapy (two deaths), and four combination therapy (one death).

The researchers concluded: "For people with bipolar I disorder, for whom long-term therapy is clinically indicated, both combination therapy with lithium plus valproate and lithium monotherapy are more likely to prevent relapse than is valproate monotherapy. This benefit seems to be irrespective of baseline severity of illness and is maintained for up to 2 years. BALANCE could neither reliably confirm nor refute a benefit of combination therapy compared with lithium monotherapy."

Lithium looks important, if it can be tolerated.

For the full abstract, click here.

The Lancet published online 23 December 2009 (doi:10.1016/S0140-6736(09)61828-6) © Elsevier Ltd 2009
Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. The BALANCE investigators and collaborators. Correspondence to::

Category: P. Psychological Keywords: lithium, valproate, monotherapy, combination, relapse, prevention, bipolar I disorder, randomized open label trial, journal watch.
Synopsis edited by Dr Stephen Wilkinson, Melbourne, Australia. Posted on Global Family Doctor 28 January 2010

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.