Lithium Plus Valproate Combination Therapy Versus Monotherapy For Relapse Prevention In Bipolar I Disorder (BALANCE). F1000: "Changes Clinical Practice"

Nader Perroud; Rudolf Uher


Faculty of 1000 

BALANCE investigators and collaborators , Geddes JR, Goodwin GM, Rendell J, Azorin JM, Cipriani A, Ostacher MJ, Morriss R, Alder N, Juszczak E
Lancet 2010 Jan 30 375(9712):385-95

Commentary from Faculty Members Nader Perroud and Rudolf Uher

Changes Clinical Practice: Based on this large trial, lithium alone or a lithium-valproate combination should be used as first-line maintenance treatment for bipolar affective disorder type I instead of valproate monotherapy.

The BALANCE trial is a milestone in the maintenance treatment of bipolar affective disorder. It is the first large study that fairly compares monotherapies, lithium and valproate, with their combination. All three regimens are frequently used but, so far, clinicians have had little guidance as to their relative merits. BALANCE shows that combination treatment or lithium monotherapy is preferable to treatment with valproate alone.

Several features make BALANCE a useful study and generalizable to clinical populations of severe bipolar affective disorder. First, it focused on bipolar affective disorder type I, characterised by full-blown manic episodes which required hospital admissions in the majority of patients. Second, all three trial arms included effective active treatment which was acceptable to the majority of severely ill patients and their clinicians. Third, an active run-in phase of combination treatment followed by independent randomisation and slow tapper off of one drug in those randomised to monotherapy assured a truly 'balanced' comparison, uncontaminated by selection or withdrawal effects. The results of BALANCE are of immediate use by practising psychiatrists in selecting a first-line maintenance treatment. It should encourage them to prescribe lithium or a lithium-valproate combination rather than valproate alone as first-line maintenance treatment for bipolar disorder type I. However, one important question remains unanswered: what will work for whom? None of the characteristics tested in BALANCE were useful in suggesting that one of the treatment choices may be more suitable for a specific subgroup of patients. Some predictors of differential efficacy of treatment with lithium and valproate that are used by clinicians, e.g. the degree of episodicity and distinction between elated and irritable mania, have not been tested in BALANCE. Therefore, clinicians will have to wait for further studies to provide any firm basis for personalising the treatment of bipolar affective disorder. The ongoing pharmacogenetic analysis of BALANCE may reveal some predictors of differential response.


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