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Logo of bmjThis ArticleThe BMJ
BMJ. 2003 August 16; 327(7411): 395–396.
PMCID: PMC1126812

Older patients are eligible for trial of lithium and valproate

John R Geddes, professor of epidemiological psychiatry
Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX
Michael J Ostacher, instructor in psychiatry

Editor—Shulman et al report an increase in the prescription of valproate for elderly patients with bipolar disorder in Canada (and corresponding decrease in prescription of lithium).1 A similar pattern has been observed in the United States over the past decade or so.2 As the authors note, this change has occurred despite the limited evidence supporting the use of valproate and may indeed reflect concerns about lithium toxicity in elderly patients.

The BALANCE trial (, which is currently recruiting in the United Kingdom and soon to begin recruiting in the United States, should provide reliable evidence about the use of both lithium and valproate in bipolar disorder.3 A recent trial comparing lithium, valproate, and placebo did not find a significant difference between the treatments, probably because the inclusion of an untreated control arm meant that it was difficult to recruit patients who were judged at substantial risk of relapse. The observed rate of relapse, and consequently statistical power, in this trial was much lower than anticipated.4,5

BALANCE does not have an untreated control group, and so recruitment of a broad range of patients should be possible to make the results applicable to most future patients. To make widespread participation feasible, BALANCE has simple procedures and does not entail additional clinic appointments or extra investigations. Unlike other trials that often routinely exclude older adults, BALANCE has no upper age restriction and so the results will directly inform practice in both younger and older patients. We therefore encourage old age psychiatrists to recruit patients so that the results will be as informative as possible.


Competing interests: None declared.


1. Shulman KI, Rochon P, Sykora K, Anderson G, Mamdani M, Bronskill S, Tran CTT. Changing prescription patterns for lithium and valproic acid in old age: shifting practice without evidence. BMJ 2003;326: 960-1. (3 May.) [PMC free article] [PubMed]
2. Fenn HH, Robinson D, Luby V, Dangel C, Buxton E, Beattie M, et al. Trends in pharmacotherapy of schizoaffective and bipolar affective disorders: a 5-year naturalistic study. Am J Psychiatry 1996;153: 711-3. [PubMed]
3. Geddes JR, Goodwin GM, Rendell JM, Hainsworth J, Van der Gucht E, Young H. New trial should clarify lithium use in bipolar disorder BMJ 2002;325: 441. [PMC free article] [PubMed]
4. Bowden CL, Calabrese JR, McElroy SL, Gyulai L, Wassef A, Petty F, et al. A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I. Arch Gen Psychiatry 2000;57: 481-9. [PubMed]
5. Baldessarini RJ, Tohen M, Tondo L. Maintenance treatment in bipolar disorder. Arch Gen Psychiatry 2000;57: 490-2. [PubMed]

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