Abstract
Gordon Johnson, Professor of Psychological Medicine, University of Sydney, Sydney, Australia:
The recent article by Oakley et al. [1] on lithium toxicity is a salutary reminder concerning a well documented risk of lithium treatment. The 97 cases of lithium poisoning treated over a 13-year period represents the largest published case series, to my knowledge, and is a significant contribution to the literature.
As this report demonstrates, lithium poisoning with attendant neurotoxicity is primarily treatment related and represents a failure of adequate clinical monitoring. Awareness of prodromal symptoms that should alert the clinician to impending intoxication are well described and include impaired cognitive function, increased tremor, unsteadiness on walking, and increased thirst [2]. Serum lithium levels do not necessarily reflect intracellular concentrations associated with chronic poisoning, and toxicity has been reported with serum levels of lithium within the accepted therapeutic range of 0.6–0.8 mmol/L, levels exceeding 1 mmol/L during maintenance treatment require review.
Unfortunately, therapeutic ranges quoted by some pathology providers of 0.6–1.2 mmol/L do not distinguish between the ranges for the treatment of mania and maintenance treatment. Maintenance lithium levels above 1 mmol/L are rarely clinically indicated and increase potential risk of neurotoxicity. Regular clinical and serum level monitoring of lithium is considered a requirement for good clinical practice; the recommendation of six monthly serum lithium estimates does not represent adequate clinical monitoring for your majority of patients.
The finding that nephrogenic diabetes insipidus is a significant risk factor for development of neurotoxicity is an important one and consistent with clinical experience, emphasizing, as the authors do, the clinical importance of assessing thirst and polyuria routinely and adjusting serum lithium levels accordingly. Research shows that there is a negative correlation between maintenance serum lithium levels and urinary concentrating ability [3]. Conversely, lithium toxicity is a significant risk factor associated with impairment of GFR and therefore lithium clearance in lithium treated patients [4].
Lithium remains the best established maintenance treatment for bipolar disorder and demands adequate clinical monitoring to minimize safety risks.