A decision analysis of long-term lithium treatment and the risk of renal failure

Division of Psychiatry, Department of Clinical Sciences, Umeå University, Sweden.
Acta Psychiatrica Scandinavica (Impact Factor: 5.61). 03/2012; 126(3):186-97. DOI: 10.1111/j.1600-0447.2012.01847.x
Source: PubMed


To establish whether lithium or anticonvulsant should be used for maintenance treatment for bipolar affective disorder (BPAD) if the risks of suicide and relapse were traded off against the risk of end-stage renal disease (ESRD).
Decision analysis based on a systematic literature review with two main decisions: (1) use of lithium or at treatment initiation and (2) the potential discontinuation of lithium in patients with chronic kidney disease (CKD) after 20 years of lithium treatment. The final endpoint was 30 years of treatment with five outcomes to consider: death from suicide, alive with stable or unstable BPAD, alive with or without ESRD.
At the start of treatment, the model identified lithium as the treatment of choice. The risks of developing CKD or ESRD were not relevant at the starting point. Twenty years into treatment, lithium still remained treatment of choice. If CKD had occurred at this point, stopping lithium would only be an option if the likelihood of progression to ESRD exceeded 41.3% or if anticonvulsants always outperformed lithium regarding relapse prevention.
At the current state of knowledge, lithium initiation and continuation even in the presence of long-term adverse renal effects should be recommended in most cases.

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Available from: Ursula Werneke, Oct 05, 2015
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    • "A critical question (Werneke et al. 2010) is when to stop lithium in a patient who develops impairment in kidney function. Such a decision should not be based exclusively on whether a patient has a slowly increasing creatinine. "
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    • "Lithium is the most widely used medication for treating bipolar disorder [4] and, although, it is highly effective at reducing the frequency and intensity of mood swings, it can be potentially dangerous. Lithium prescribed in the form of carbonate (Li2CO3) or citrate has a very narrow therapeutic range (concentrations ranging from 0.4 to 1.0 mM) with the upper limit being uncomfortably close to toxic levels [5]. "
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    ABSTRACT: Lithium medication is the gold standard of treatment in Bipolar Disorder patients, preventing and reducing mood swings and suicidality. However, despite its effectiveness, it is a potentially hazardous drug requiring regular monitoring of blood levels to ensure toxic levels are not reached. This paper describes the first steps towards developing a new portable device that can be used by Bipolar Disorder patients to facilitate the analysis of lithium blood levels at home. Solutions of lithium carbonate have been optically fingerprinted using a high-end spectrophotometer. Preliminary measurements indicate that while the visible to near infrared region of the absorption spectra fall heavily within the water band, measurements in the Ultraviolet region show a strong distinction between different lithium concentrations. The optical spectra of Lithium in the 220 nm to 230 nm region demonstrated the ability to differentiate between concentrations representing those found in patients.
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    • "On the other hand, the incidence of ESRD is considered uncommon based on data from renal dialysis and transplant registers [10]. In any case, the risk of renal failure needs to be weighed against the benefits obtained, as recently reported by Werneke et al. [11], who conducted a decision analysis simulating the decision process between physicians and patients, comparing the relative risks and utility of maintenance treatment. The analysis addressed two questions: 'Should lithium be recommended at the beginning of treatment in view of a small but significant risk of ESRD later in life?' and 'Should lithium continuation be recommended even in the presence of long-term adverse renal effects?' "
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    ABSTRACT: Background: The adverse renal effects of lithium have long been known, but glomerular insufficiency had been considered an unlikely event until recently, when new studies have raised concern regarding very long-term treatment. In this cross-sectional study, we examined glomerular function in a cohort of patients treated with lithium for up to 33 years and a control group of lithium-naïve patients treated with other mood-stabilizers. Methods: Patients with a diagnosis of recurrent or persistent affective disorders, examined between 1 October 2007 and 31 December 2009, were screened. Demographic and clinical data were extracted from clinical charts regarding two study groups: one for patients treated with lithium for at least 12 months and the other for patients never exposed to lithium. Multivariate regression analysis was applied: the dependent variable was the estimated glomerular filtration rate (eGFR) calculated from the last available serum creatinine value using the Modification of Diet in Renal Disease Study Group equation; the following independent variables, potentially associated with renal dysfunction, were included: gender, current age, duration of lithium treatment, cigarette smoking, hypertension, diabetes and dyslipidemia. Results: eGFRs lower than 60 ml/min were significantly more frequent in the group treated with lithium (38/139 = 27.3%) compared to lithium-naïve patients (4/70 = 5.7%) (P = 0.0002; Fisher's test). Regression analysis showed a significant effect on eGFR of age, gender and duration of lithium treatment but no effect of cigarette smoking, hypertension, diabetes or dyslipidemia. eGFR was estimated to decrease by 0.64 ml/min (95% confidence interval = 0.38 to 0.90; P = 0.00) for each year of lithium treatment. Conclusions: The duration of lithium treatment is a risk factor for glomerular failure, in addition to advancing age. For example, all patients aged 60 years or older may be estimated to undergo Stage 3 or more severe chronic kidney disease (namely an eGFR less than 60 ml/min) if treated with lithium for 30 years. These data may be added to the current debate on the balance between the protective effects of lithium on recurrent affective disorders and suicide and the risk of renal disease.See related commentary article here
    BMC Medicine 02/2013; 11(1):33. DOI:10.1186/1741-7015-11-33 · 7.25 Impact Factor
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