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Lithium is not as widely used for relapse prevention in bipolar disorder as perhaps it should be. However, the main reason is simple. It is perceived to be an unsafe drug and, in practice, this requires us to monitor its serum levels and the renal and endocrine function of patients who take it long term. At both an emotional and a practical level, the harm lithium may do weighs heavy in the minds of physicians and perhaps also their patients.
The study by Kessing et al1 in this issue of JAMA Psychiatry examines the relationship between a bipolar diagnosis, drug exposure, and the risk of renal disease, probably the main focus for safety concerns. By linking the national databases in Denmark, it represents a comprehensive test of how an entire population fares in a socialized medical care system with a strong historical tradition of using lithium. Renal disease is variously described but ultimately defined by declining glomerular function. End-stage renal failure is a hard, potentially fatal outcome and is unlikely to be affected by any marked bias in detection: in Denmark it was ascertained from the national transplantation and dialysis register. Possible or definite renal disease short of renal failure is much more common and may or may not have functional consequences. Stage 3 of chronic renal disease, from which point patients may develop symptoms, is defined by a glomerular filtration rate less than 60 mL/min/1.73 m2. Its detection will obviously be increased by frequent monitoring and, while a necessary prelude to end-stage renal failure, it is rarely sufficient: rates of end-stage renal failure are low (about 1 case in every 530 persons or 6861 person-years’ observation in the Danish registers).
Goodwin GM. The Safety of Lithium. JAMA Psychiatry. 2015;72(12):1167-1169. doi:10.1001/jamapsychiatry.2015.2014