ABSTRACT
Lithium has long been accepted as the first-line therapy for relapse prevention in bipolar disorder. Early skepticism1 was at least partly dispelled by a clearer documentation of the usually adverse course of the illness and by randomized clinical trials, exemplified by the seminal Veterans Administration-National Institute of Mental Health (VA-NIMH) trials conducted by Robert Prien and his colleagues2. However, uncertainty about the effectiveness of lithium in real-life practice continued. This was fueled in the 1990s by retrospective attacks on the validity of the pivotal efficacy trials conducted in the 1970s3, concern about toxicity and the increased risk of relapse on withdrawal4,5, and the introduction and marketing of potential alternative drug treatments, particularly valproate semisodium (Depakote®). Most recently, and a little unexpectedly, new longterm evidence has emerged from large trials conducted primarily to investigate the efficacy of newer agents compared with placebo, but
which also included a lithium arm as an active comparator6. In this chapter, we summarize the randomized evidence for the long-term efficacy of lithium in the prevention of relapse in bipolar disorder, suggest a method for the clinical application of the randomized evidence to the individual patient and provide a regimen for baseline assessment and monitoring for patients taking long-term lithium therapy.
