Lithium therapy in bipolar disorder: a balancing act?

www.thelancet.com Vol 386 August 1, 2015 415 Quite reasonably, patients with bipolar disorder want treatment that provides sustained relief from their illness without incurring serious side-eff ects. Functionally, this translates to the resumption of purpose and enjoyment. But of the numerous drugs available for the management of bipolar disorder, only lithium seems to truly stabilise mood. Its status as an eff ective prophylactic agent was convincingly reinstated by the fi ndings of the randomised, open-label BALANCE trial, which corroborated empirical knowledge. The BALANCE investigators showed that lithium alone, or lithium plus valproate, are more likely to prevent relapse than valproate monotherapy, and prophylaxis with lithium monotherapy might be on a par with lithium plus valproate. Hence, despite fl uctuating popularity, lithium remains a fi rst-line option for the treatment and prophylaxis of bipolar disorder in therapeutic guidelines. However, use of lithium in practice is limited by concerns about safety and adverse eff ects with long-term use. Extending previous research that examined the short-term tolerability of lithium, in The Lancet Brian Shine and colleagues have drawn on a large set of data to determine the long-term eff ects of lithium on renal and endocrine function. Data from 4678 patients were included in the study, of whom 2795 had their serum lithium measured more than once. Shine and colleagues’ fi ndings show that lithium was associated with increased risk of stage three chronic kidney disease (estimated glomerular fi ltration rate <60 mL/min/1·73m2; hazard ratio 1·93, 95% CI 1·76–2·12), hypothyroidism (thyrotropin activity >5·5 mU/L; 2·31, 2·05–2·60), and hypercalcaemia (1·43, 1·21–1·69). These fi ndings send a key message to clinicians to monitor lithium therapy closely from the outset. Both thyroid hormone secretion and renal function can decline with long-term lithium use and can, in some cases, lead to hypothyroidism and stage three chronic kidney disease. Interestingly, these complications are more likely to occur in women than in men, and are detected early in the course of lithium treatment. In addition, long-term lithium therapy can also cause hypercalcaemia (ie, total plasma calcium concentration ≥2·6 mmol/L). All adverse eff ects are more likely to occur when plasma lithium concentration is high. Therefore, patients receiving lithium therapy should have thyroid function, renal clearance, and blood calcium concentrations assessed carefully at the beginning of therapy and monitored closely thereafter. Shine and colleagues provide clear evidence of the potential risks associated with long-term lithium treatment. But because bipolar disorder typically emerges at a young age and requires lifelong treatment, these fi ndings prompt the question: how can these hazards be navigated? The answer is twofold. First, avoid sustained periods during which plasma lithium concentrations are high to diminish the risk of serious adverse eff ects. Second, all the parameters that need regular assessment, such as thyroid and renal function tests and plasma lithium and calcium concentrations, can be measured reliably and easily. However, the treatment of type I bipolar Lithium therapy in bipolar disorder: a balancing act?