Long-term Lithium Treatment Research Articles

Distress due to lithium‐induced polyuria: Exploratory study

Lithium-induced polyuria, although common, often goes unrecognized. The purpose of the present study was therefore to investigate the complaints of polyuria, and distress and functional impairment associated with polyuria, in 56 patients with bipolar disorder on long-term lithium treatment. All participants underwent 24-h urine collection, and renal function tests. Polyuria (24-h urine volume > 3 L) was found in 70% of subjects. Unless directly enquired about, polyuria was underreported. Impairment in work and daily routine due to increased urine output/frequency was associated with 24-h urine volumes. Polyuria is a highly prevalent, distressing and impairing side-effect of long-term lithium treatment, requiring due attention.

Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment. To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ(42)), total tau (T-tau), phosphorylated-tau) (P-tau). NCT01055392. Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.

Pharmacological reversal of synaptic plasticity deficits in the mouse model of Fragile X syndrome by group II mGluR antagonist or lithium treatment

Fragile X syndrome is the leading single gene cause of intellectual disabilities. Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate receptor (mGluR) antagonists or lithium rescues social and cognitive impairments. A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long-term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the hippocampus. Here we examine the effects of chronic treatment of Fragile X mice in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses. We find that long-term lithium treatment initiated during development (5–6 weeks of age) and continued throughout the lifetime of the Fragile X mice until 9–11 months of age restores normal mGluR-LTD. Additionally, chronic short-term treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of Fragile X syndrome is an important advance, in that this identifies and validates these targets as potential therapeutic interventions for the treatment of individuals afflicted with Fragile X syndrome.

Implication of synapse-related genes in bipolar disorder by linkage and gene expression analyses.

Several chromosomal regions have been linked to bipolar disorder (BD). However, the search for specific genes has been hampered by inconsistent findings, partly due to genetic and phenotypic heterogeneity. We focused on lithium-responsive bipolar patients, a subgroup thought to be more homogeneous and conducted a multistage study including an initial linkage study followed up by fine mapping and gene expression. Our sample consisted of 36 families (275 genotyped individuals, 132 affected) recruited through probands who were responders to long-term lithium treatment. We conducted a genome-wide scan with 811 microsatellite markers followed by fine mapping. Gene expression studies of candidate regions were conducted on six post-mortem prefrontal brain regions of 20 individuals (8 BD and 12 controls). We identified regions 3p25, 3p14 and 14q11 as showing the highest genome-wide linkage signal (LOD 2.53, 2.04 and 3.19, respectively). Fine mapping provided further support for 3p25, while only modest support was found in the other two regions. We identified a group of synaptic, mitochondrial and apoptotic genes with altered expression patterns in BD. Analysis of an independent microarray dataset supported the implication of synapse-related and mitochondrial genes in BD. In conclusion, using two complementary strategies, we found evidence of linkage to lithium-responsive BD on 3p25, 3p14 and 14q11 as well as significantly dysregulated genes on these regions suggesting altered synaptic and mitochondrial function in BD. Further studies are warranted to demonstrate the functional role of these genes in BD.

Serum Brain-Derived Neurotrophic Factor in Euthymic Bipolar Patients on Prophylactic Lithium Therapy

Aim: The aim of the study was to evaluate serum brain-derived neurotrophic factor (BDNF) levels in a group of euthymic bipolar patients on long-term prophylactic lithium treatment and to delineate putative relationships between lithium efficacy and BDNF concentrations. Methods: 141 euthymic bipolar patients (51 male, 90 female) on long-term lithium treatment were studied. Three categories of prophylactic lithium response were delineated: excellent lithium responders (ER; 30 patients), partial lithium responders (PR; 61 patients) and lithium nonresponders (NR; 50 patients). The control group consisted of 75 age- and gender-matched healthy subjects. Results: The lithium-treated patients as a whole group had lower BDNF levels compared to the healthy controls. However, after breaking down the patients into ER, PR and NR, it appeared that only NR had significantly lower BDNF levels compared with the healthy control subjects. No association between the age of the patients, duration of bipolar illness, and serum lithium and BDNF levels was found. Conclusion: The results point to a relationship between lithium prophylactic efficacy and plasma BDNF levels in euthymic bipolar patients where lithium NR had reduced BDNF levels. These findings suggest that serum BDNF is associated with lithium efficacy in bipolar disorder.

Long-term lithium treatment for patients with mild cognitive impairment: Benefits on cognition and evidence of disease modification

Long-term lithium treatment for patients with mild cognitive impairment: Benefits on cognition and evidence of disease modification

Effects of chronic lithium treatment on renal function

Introduction Lithium treatment is associated with renal side effects which vary from mild nephrogenic diabetes insipidus to end stage renal disease (ESRD). A review of the literature suggests that ESRD is a very rare side effect, caused after very long-term lithium treatment, and that it might be preventable if lithium is stopped early. Methods Sixty-one patients were treated with lithium for a mean of 15.6 years (range 3–32, SD = 6.4). Their kidney function was monitored at an Affective Disorders Clinic for a mean of 11.5 years (range 2–29, SD = 5.4). We estimated their glomerular filtration rate (eGFR) at the end of monitoring. As a control group we used 53 patients who received ECT at our hospital, and had not taken lithium, and nine patients from the same clinic who were taking other mood-stabilisers. Results Lithium patients had lower eGFR compared to controls: 66.1 vs. 75.0 mL/min/1.73 m 2, p = 0.0006 after controlling for age and gender. The percentage of patients with an eGFR < 60 ml/min/1.73 m 2 (grade 3 chronic kidney disease) was 34.4%, vs. 13.1% in the controls, and was much increased compared to the general population in the respective age ranges. There was a modest but non-significant correlation between the number of years that patients had taken lithium and their eGFR, (beta = − 0.177, B = − 0.43, p = 0.1). One patient reached an eGFR of 28 mL/min/1.73 m 2 and her lithium was stopped. One patient required dialysis 6 years after leaving the clinic. Conclusions Lithium causes a modest decline in renal function. However the available research suggests that ESRD is a very rare complication of long-term lithium treatment, affecting ∼ 1% of patients who have taken lithium for over 15 years.

Chronic Lithium Impairs Skin Tolerance to Ischemia in Random-Pattern Skin Flap of Rats

Despite its apparent anti-apoptotic effect, lithium impairs endothelium-dependent vasorelaxation in various tissues. In this study, we assessed the effect of lithium treatment on ischemic skin flap survival and its interaction with nitric oxide pathway. Seventy-six male Sprague-Dawley rats were randomly assigned into 13 groups. For skin flap surgery, dorsal skin flap measuring 8 × 2 cm was elevated on the midline. After local injections (if needed), the cranial pedicle was cut and flap was sutured back. Flap survival was assessed after 7 d. Animals in the chronic lithium group received lithium chloride in tap water for 4 wk preoperatively and 7 d postoperatively. Acute lithium groups received 3 nmol, 10 nmol and 3 μmol/flap lithium locally. In another experiment, interaction with nitric oxide synthase inhibitor L-NAME as well as nitric oxide precursor L-arginine was studied, and the effect of ischemic preconditioning on skin flap survival in lithium treated rats was investigated. Chronic lithium group had mean flap survival value of 32.6% ± 5.2% (mean ± SD), which was significantly lower than normal subjects (52.7% ± 6.1%, P < 0.001), while acute local lithium treatment had no effect. In chronic lithium group, systemic L-NAME (10 mg/kg, 30 min before flap elevation) failed to significantly decrease the survival, while sub-effective systemic L-arginine (100 mg/kg) and ischemic preconditioning significantly increased flap survival (P < 0.001 and P < 0.01, respectively). We conclude that long-term lithium treatment impairs the skin tolerance to ischemia in rats, which seems to be nitric oxide mediated. This effect is prevented by ischemic preconditioning or L-arginine treatment. The results suggest that skin-involving interventions should be applied more cautiously in patients who are on lithium treatment.

Renal failure occurs in chronic lithium treatment but is uncommon

We sought to establish the prevalence of lithium-induced end-stage renal disease in two regions of Sweden with 2.7 million inhabitants corresponding to about 30% of the Swedish population. Eighteen patients with lithium-induced end-stage renal disease were identified among the 3369 patients in the general lithium-treated population, representing a sixfold increase in prevalence compared with the general population for renal replacement therapy. All lithium-treated patients were older than 46 years at end-stage renal disease with a mean lithium treatment time of 23 years with ten patients having discontinued lithium treatment an average of 10 years before the start of renal replacement therapy. The prevalence of chronic kidney disease (defined as plasma creatinine over 150 micromol/l) in the general lithium-treated population was about 1.2% (excluding patients on renal replacement therapy). Compared with lithium-treated patients without renal failure, those with chronic kidney disease were older and most were men but, as groups, their mean serum lithium levels and psychiatric diagnoses did not differ. We found that end-stage renal disease is an uncommon but not rare consequence of long-term lithium treatment and is more prevalent than previously thought. Time on lithium was the only identified risk factor in this study, suggesting that regular monitoring of renal function in these patients is mandatory.

S20-01 - Parathyroid hormone and cognitive deficits in lithium-treated bipolar patients

IntroductionLong-term lithium-treatment has been associated with deficits in several cognitive domains in euthymic bipolar patients. At the same time, long-term lithium treatment is also associated with an increase in parathyroid levels, often without a concomitant increase in calcium levels. Such an isolated increase in parathyroid levels has been linked to depressive symptoms and cognitive deficits in otherwise healthy individuals.AimsTo investigate whether increased parathyroid levels are associated with cognitive deficits in euthymic bipolar patients.MethodsWe plan to recruit 30 euthymic bipolar patients on lithium treatment for this study. Patients will take part in several neuropsychological tests, covering executive functioning, memory and attention. In parallel, blood levels of lithium, parathyroid hormone, 25-hydroxyvitamin D, creatinine, calcium and phosphate will be assessed, besides clinical chemistry and blood cell count. In addition, to account for potential confounders, a variety of clinical variables will be recorded, including established mood rating scales and demographic variables as well as further parameters relevant to the course of the illness.ResultsAs the study is still ongoing results are not available yet at this moment.DiscussionResults will be discussed in the context of previous studies examining the impact of lithium and parathyroid hormone on mood and cognition in healthy individuals and patients with bipolar disorder, respectively. Dependent on the outcome of this study, potential future studies, including intervention trials aiming at lowering increased PTH levels in bipolar patients on lithium will be outlined.

S23-01 - Lithium treatment and the risk of suicide in affective disorders

In spite of the fact that suicidal behaviour is very complex, multicausal human behaviour, untreated current major Axis I affective disorder (bipolar and unipolar major depressive episode: 56-87%) is the most powerful predictor of suicide, particularly in the case of prior suicide attempt. Prospective and retrospective follow-up studies clearly support the eivedent clinical observation that if patients with unipolar or bipolar mood disorder committ or attempt suicide, they do it mostly during the major depressive episode (78-89%) and less frequently in dysphoric mania or mixed affective episode (11-20%) but very rearly during euphoric mania or euthymia, indicating that suicidal behaviour in mood disorder patients is a state-dependent phenomenon. Consequently, effective treatment of acute major mood episodes and successful long-term management is very important part of suicide prevention of patients with affective disorders. Indeed, it has been repeatedly demonstrated that long-term lithium treatment of bipolar disorder and unipolar depression reduces the risk of completed and attempted suicide markedly, even in this high-risk population. The marked anti-suicidal potential of lithium seems to be more than the simple reflexion of its phase-prophylactic effect, as it has been demonstrated that during the long-term prophylaxis of recurrent unipolar and bipolar affective disorder patients with at least one prior suicide attempt, a significant reduction in the number of suicide attempts was found not only in the excellent responders (93%), but also in moderate responders (83%) and in poor responders (49%).

Lithium response across generations

To describe and integrate observations from bipolar patients responsive to lithium stabilization and their children. Selected findings are described from the clinical and biological investigations of adults meeting research criteria for bipolar disorder and for responsiveness to lithium stabilization; and from prospective studies of the children of lithium responders and non-responders. Response to prophylactic lithium identifies a valid subtype of bipolar disorder, however the search for biological markers of lithium response, while promising, has so far remained inconclusive. Adult responders to lithium stabilization exhibit definable clinical features which are also observable in their affected children. In prospective studies the children of bipolar parents develop symptoms earlier than reported previously, with marked differences between the offspring of lithium responders and non-responders. The illness evolves in predictable clinical stages, first from non-specific sleep and anxiety disorders to mood symptoms and then, often starting in adolescence, major depressive and later activated episodes. Investigating and comparing unequivocal responders and non-responders to long-term lithium treatment and their offspring is a fertile research strategy for addressing a multitude of clinical and research questions.

Long-term lithium treatment in the prevention of suicidal behavior in bipolar disorder patients

We reviewed available research findings, including meta-analyses on effects of lithium-treatment associated with rates of suicidal behavior in bipolar disorder or unipolar major depressive disorder patients, and for comparisons of lithium to mood-stabilizing anticonvulsants. Data from meta-analyses consistently indicate marked reductions of suicidal behavior and mortality during long-term treatment with lithium salts in bipolar disorder patients, and possibly also in unipolar, recurrent major depressive, perhaps even more effectively than with anticonvulsants proposed as mood-stabilizers. Suicidal risk is frequently associated with dysphoric-agitated symptoms, anger, aggression, and impulsivity-all of which may respond better to treatment with lithium or other mood-stabilizing medicines than to antidepressants. In these conditions, antidepressant treatment may not provide a beneficial effect on risk of suicidal thoughts and perhaps attempts, particularly in juveniles, whereas, lithium, perhaps even more than anticonvulsants, seems to be remarkably effective in the preventing suicidal behavior. The mechanism of action is not well defined and may be associated with either a prevention of mood recurrences or a more specific "antisuicidal" activity.

Effects of Lithium on Cognitive Performance

Cognitive impairment is underrecognized among patients with bipolar disorder and may represent not only effects of the illness but also adverse effects of its treatments. Among these, lithium is the best-studied mood stabilizer. As its cognitive effects are mixed and not well-known, we assessed reported effects of lithium on cognitive performance. MEDLINE, PsycINFO, and EMBASE databases (1950 to December 2008) were queried with the keywords lithium, cognit*, neurocognit*, neuropsych*, psycholog*, attention, concentration, processing speed, memory, executive, and learning. Database searches were supplemented with bibliographic cross-referencing by hand. The literature search was conducted independently by 2 authors (A.P.W. and T.S.W.) during August and September 2008, and questions about appropriate inclusion or exclusion were resolved between them by consensus. Of 586 reports initially identified as being of potential interest, 12, involving 539 subjects, met our inclusion criteria: (1) cognitive performance compared between subjects taking lithium and comparable subjects not taking lithium; comparability was assured by: (2) patients with the same affective disorder diagnoses in euthymic or remitted status or healthy volunteers; (3) groups of similar age and sex; (4) similar intelligence, education, or occupation; (5) similar distribution of other concurrent psychotropic drugs; and (6) cognitive abilities (outcomes) assessed with performance-based measures. Standardized mean-difference effect size (ES), corrected for small-sample bias (Hedges' g), was computed for cognitive tasks in each study. ES estimates were transformed so that positive values indicate poorer performance by lithium-treated subjects. Infrequently, when means and standard deviations were not provided, ES was estimated from reported values of t, F, or z tests. For analysis, similar neurocognitive tests were grouped a priori based on the cognitive domains they aimed to assess. We identified 12 studies involving 276 lithium-treated and 263 similar or the same subjects, lithium-free. Lithium was taken for a mean duration of 3.9 years by affective disorder patients and 2.5 weeks by healthy volunteers, yielding a mean daily trough serum concentration of 0.80 mEq/L. Overall, lithium treatment was associated with small but significant impairment in immediate verbal learning and memory (ES = 0.24; 95% CI, 0.05-0.43) and creativity (ES = 0.33; 95% CI, 0.02-0.64), whereas delayed verbal memory, visual memory, attention, executive function, processing speed, and psychomotor performance were not significantly affected. Selectively, among the 326 affective-disorder patients, in addition to these overall impairments, long-term lithium treatment also was associated with even greater impairment in psychomotor performance (ES = 0.62; 95% CI, 0.27-0.97), with no evidence of cognitive improvements. Lithium treatment appears to have only few and minor negative effects on cognition.

Lithium: Updated Human Knowledge Using an Evidence-Based Approach

Lithium use in mental diseases has changed over the years but remains a cornerstone of treatment in bipolar disorders. In two companion papers, we have reviewed existing (and especially recent) data on lithium efficacy and updated basic knowledge regarding the practical fundamentals of lithium therapy. The present paper reviews safety data on lithium available to date. Gastrointestinal pain or discomfort, diarrhoea, tremor, polyuria, nocturnal urination, weight gain, oedema, flattening of affect and exacerbation of psoriasis are typical complaints of patients receiving long-term lithium therapy. Renal involvement results in a reduced urinary concentrating capacity, expressed as obligate polyuria, with secondary thirst. With long-term therapy, this may result in nephrogenic diabetes insipidus. In addition, glomerular filtration rate falls slightly in about 20% of patients. The view that only a few patients receiving long-term lithium are at increased risk of glomerular impairment and progressive renal insufficiency should be regarded with caution. The risk is increased in case of concomitant diseases or medications. Lithium treatment may inhibit thyroid hormone release and induce goitre. Consequently, the prevalence of both overt and subclinical hypothyroidism is increased, with circulating thyroid auto-antibodies frequently being found. Much less commonly, thyrotoxicosis may also develop in association with lithium therapy. Long-term lithium treatment may also be associated with persistent hyperparathyroidism and hypercalcaemia, as well as with hypermagnesaemia. Overweight of up to 4-10 kg is found in approximately 30% of lithium-treated patients. Most neurological manifestations are benign, for example, the fine postural and/or action tremor present in 4-20% of patients. This is increased by high caffeine consumption and concomitant use of other psychotropic agents. A number of rare, potentially serious neurological adverse effects have been reported, including extrapyramidal symptoms, 'pseudotumour cerebri' or occasionally cerebellar symptoms. Severe neurological sequelae are exceptional. Cognitive disturbances are often mentioned as a lithium-related adverse effect. The few controlled studies do show a statistically significant negative effect of lithium on memory, vigilance, reaction time and tracking. There are frequent reports of mild effects of lithium on cognition at therapeutic serum concentrations. A number of deaths associated with lithium treatment have been reported. The most serious issue is that of non-accidental overdose, i.e. either long-term overdosage or acute overdose on long-term treatment. Progressive renal insufficiency, an exceptional complication of long-term lithium therapy, may also have a fatal outcome. In relation to pregnancy, lithium salts are rated as category D (positive evidence of risk). Therefore, prescription of lithium should be avoided during the first trimester of pregnancy unless the benefit to the mother exceeds the risk to the fetus. Although lithium transfer into breast milk is well established, the long-term fate of babies breast-fed by mothers receiving lithium therapy is unknown. Whether lithium therapy is safe in breast-feeding women is controversial. Although there is no absolute contraindication, it is known that the kidney is particularly sensitive to lithium just after birth. Intoxication in patients on long-term treatment with lithium in the absence of history of acute ingestion is not rare. Contributing factors include change in daily dose, long-term high dosage, kidney disease or drug interaction. In suspected cases, serum concentrations should be obtained early and repeatedly. In addition to supportive measures, haemodialysis is the treatment of choice for severe cases. Thorough knowledge of the limitations and drawbacks of lithium therapy is mandatory for its optimal use, especially at a time when its risk/benefit profile needs to be compared accurately with that of antiepileptic drugs and other mood stabilizing medications.

Complications rénales chroniques induites par le lithium : revue de la littérature

After 40 years of use of lithium in the treatment of mood disorders, the renal risks associated with the long-term exposure to lithium are better known. This review is aimed at summarizing the information available in the literature regarding the impact of lithium on renal structure and function, the prevalence of renal abnormalities, the associated risk-factors and the strategy for their identification and management. Articles were selected using a Medline search. The keywords were lithium, renal function, kidney, nephrotoxicity, renal insufficiency, side-effects, polyuria, diabetes insipidus and drug monitoring. A well-recognized adverse effect of lithium exposure is the occurrence of nephrotic diabetes insipidus (NDI) resulting in polyuria and polydipsia, which occurs in 20% of the patients on long-term lithium treatment. This side-effect is linked to a deficit in urine concentrating ability. Its occurrence is associated with the duration of lithium therapy. Although this effect of lithium is initially functional and may disappear if the treatment is rapidly stopped, it may become structural and permanent over time. The decision to stop lithium or to treat the NDI with amiloride is mainly based upon its functional impact. A debate has been ongoing for decades regarding whether or not the long-term use of lithium may cause slowly progressive renal failure. According to the recent literature, progressive renal failure occurs in approximately 20% of the patients on long-term lithium treatment, among whom a few develop severe renal insufficiency due to lithium (possibly in conjunction with other somatic factors) in the form of interstitial nephritis. However, there is an increasing number of reports of patients requiring dialysis after long-term exposure to lithium. Current recommended strategies for minimising the renal side effects of lithium include: avoiding acute episodes of renal toxicity; monitoring serum lithium concentrations in order to achieve optimal efficacy at the lowest possible concentrations; monitoring serum creatinine levels at least on a yearly basis, with discontinuation of lithium use, discussion with a nephrologist if creatinine clearance decreases below 60 ml/mn; and the possible application of lithium into single daily dose.

Transient Hypnic Headache Syndrome in a Patient With Bipolar Disorder After the Withdrawal of Long-Term Lithium Treatment: A Case Report

Transient Hypnic Headache Syndrome in a Patient With Bipolar Disorder After the Withdrawal of Long-Term Lithium Treatment: A Case Report

Long-Term Effectiveness of Lithium in Bipolar Disorder

Poor response to long-term lithium treatment has been reported to be associated with atypical features of bipolar disorder. The purpose of this study was to investigate the influence of atypical symptoms on the effectiveness and stability of long-term lithium treatment in a prospective, multicenter cohort of bipolar patients in a naturalistic setting. Patients were initially selected according to International Classification of Diseases, 8th Revision, criteria for bipolar disorder and required long-term treatment. Their diagnoses were reconfirmed according to DSM-IV upon its publication. They were prospectively followed for an approximately 20-year period ending in 2004 in 5 centers participating in the International Group for the Study of Lithium-Treated Patients. Examinations included a comprehensive psychiatric evaluation, an assessment of typical and atypical features on an 8-item scale, and an evaluation of clinical course using the morbidity index. Unbalanced repeated-measures regression models with structured covariance matrices were used to assess the extent to which the morbidity index was influenced by atypical symptoms, duration of treatment, and pretreatment features. A total of 242 patients were followed for a mean period of 10 years. In 142 patients, the number of typical features was greater than the number of atypical features, whereas in 100 patients the number of atypical features was greater than or equal to the number of typical features. The mean morbidity index remained stable over a period of 20 years in both groups of patients and was not significantly associated with the presence of atypical features, the duration of lithium treatment, the number or frequency of episodes, or latency from the onset of bipolar disorder to the start of lithium treatment. Our study suggests that long-term response to lithium maintenance treatment is stable both in patients with typical and in patients with atypical features. The predominance of either typical or atypical features did not result in different responses to long-term lithium treatment in this sample of bipolar patients.

Lithium nephropathy in Sweden

Background and Aims:Uncertainty prevailing about the role of lithium for the development of chronic renal failure; and the prevalence of lithium-induced end-stage renal disease (ESRD) being virtually unknown, we decided to clarify these issues.Methods:Using a questionnaire we counted the number of former or present lithium patients among all ESRD patients on renal replacement therapy (RRT, i.e. dialysis or renal transplant) in two defined regions in Sweden, comprising 30 % of 9 million Swedes. We also counted the number of all lithium patients in the areas. A chart review is under way to retrieve clinical data for the assessment of the nephrotoxic effect of the lithium therapy.Results:There were 2,270 RRT patients (0.08 % of the general population). Twenty-seven of them (1.2 %) acknowledged long-term lithium treatment. Seventeen were on dialysis, ten were transplanted. The concurrent number of lithium patients was 3,567.Based on our own earlier studies we estimate that 900 (25 %) of the lithium patients in the two regions had been on lithium ≥15 years. Thus, twenty-seven of the long-term lithium patients in this study were subject to RRT.Conclusions:The prevalence of lithium nephropathy in the RRT population is at least 1 %, 0.8 % in the entire lithium population, and approximately 3 % among long-term lithium patients. The risk of developing ESRD is higher when on lithium therapy compared to the general population. Our results so far underscore the need for adequate safety programs, ascertaining the early detection of lithium nephropathy.

Neurocognitive Impairment and Dementia in Mood Disorders

Neurocognitive Impairment and Dementia in Mood Disorders