Effect of acute alcohol consumption on lithium kinetics

2016

Background : Lithium has been commonly used for the treatment of several mood disorders particularly bipolar disorder in the last 60 years. This study aimed to analyze patients with lithium intoxication referred to Loghman- Hakim teaching hospital. Methods: This is a cross sectional study that has been done on 108 patients with lithium intoxication during 2001 to 2010. Necessary data were collected by checklists and then analyzed by statistical methods in SPSS version 20. Results: 39.8% of patients were male and most of them were in age group 20-40 years (47.2%). The rate of lithium use in 66.7% of patients was lower than 20 grams and the level of lithium in blood was 1 mEq/lit in 44.4% of patients. The rate of recovery has been significantly relation with BUN, creatinin, Intubation, pCO2 and pH. There was a significant relation between hospitalized with pH, pCO2, Na, absorbent materials, intubation and bicarbonate. Conclusion: Results showed that we should note to the rate and time...

The American Journal of Medicine, 1979

Indian journal of psychiatry, 1981

Eighteen physically healthy volunteers were given 1200 mg of standard and sustained-release preparations of lithium on two different occasions. Serum lithium levels were estimated at four hourly intervals and statistically analysed. The findings and the results have been discussed with particular reference to their implications for future research.

CNS Drugs

Although there has been a decrease in lithium use over several years, it is still recommended as a first-line mood stabilizer in all recent guidelines. It has been argued that many studies of lithium were conducted at a time when study design, assessment standards and the diagnostic criteria for patient selection were not as established as they presently are. However, recent placebo-controlled data from three-arm trials have demonstrated a definite efficacy of lithium in bipolar disorder. Regarding mania, recent trials of novel antimanic treatments (such as second-generation antipsychotics) that have included both placebo and lithium control groups have confirmed that lithium is effective in the treatment of moderate to severe manic episodes. The efficacy of lithium as monotherapy for acute bipolar depression is still controversial, but this therapy is recognized as a therapeutic option. For maintenance therapy, lithium is superior to placebo for the prevention of relapse or recurrence of mood episodes in bipolar I disorder patients with recent manic or hypomanic episodes. Lithium is more effective in preventing episodes of the manic/hypomanic type, including mixed episodes, than preventing depressive episodes. In rapid cycling patients, lithium improves clinical symptoms as efficiently as in nonrapid cycling persons, but is not likely to prevent recurrences. Finally, data from a number of studies suggest that lithium reduces the high suicide rates associated with mood disorders. A well designed cohort study and two independent meta-analyses are in agreement with this finding. In conclusion, most experts, and the most recent guidelines, continue to consider lithium as a keystone therapy of bipolar disorders.

Journal of The American Society of Nephrology, 1999

Normally, lithium is not present in significant amounts in body fluids (Ͻ0.2 mEq/L). However, lithium salts have been used therapeutically for almost 150 years, beginning with its use for the treatment of gout (or uric acid diathesis) in the 1850s (1). Although gout was believed to include symptoms of mania and depression, it wasn't until the 1880s that John Aulde and Carl Lange observed that lithium could be used to treat symptoms associated with depression, independent of gout (1). However, the use of lithium became problematic and was discarded due to the serious toxicity associated with the widespread use of lithium in tonics, elixirs, and as a salt substitute (1). The modern era of lithium usage as a pharmacologic agent began with its "rediscovery" in 1950 by Cade and the clinical studies by Schou in the 1950s that established lithium as an effective treatment of manic-depressive illness (1). Lithium is now the drug of choice for treating bipolar affective disorders. It is successful in improving both the manic and depressive symptoms in 70 to 80% of patients (2). Lithium may also be used to treat alcoholism, schizoaffective disorders, and cluster headaches (3). Thus, lithium is an indispensable pharmaceutical component of modern psychiatric therapy. Unfortunately, lithium also has a narrow therapeutic index, with therapeutic levels between 0.6 and 1.5 mEq/L (Table 1) (2-4). The optimal steady-state concentration of lithium for maintenance treatment of bipolar disorders is generally considered to be 0.6 to 1.2 mEq/L, with slightly elevated steadystate concentrations (0.8 to 1.5 mEq/L) indicated for the acute management of manic episodes (5). Because toxicity can occur at levels Ͼ1.5 mEq/L, lithium levels must be carefully monitored and lithium dosage adjusted as necessary. This is especially true following changes in other medications that alter renal function, such as angiotensin-converting enzyme (ACE) inhibitors or nonsteroidal anti-inflammatory drugs (NSAID). Nephrologists require a thorough understanding of lithium since it is excreted by the kidney and its toxic side effects commonly affect renal function. In addition, the treatment of lithium intoxication usually requires consideration of the need for acute hemodialysis, a decision that should only be made by a nephrologist.

Bipolar Disorders, 2005

Lithium salts are first choice agents for the longterm prophylaxis and acute treatment of several psychiatric disorders (1-3). A strong relationship between lithium serum levels and both its efficacy and its toxicity has been established (4-8). The narrow therapeutic window together with the high inter-and intra-individual variability in pharmacokinetics and sensitivity to its effects, necessitates regular therapeutic drug monitoring of patients receiving lithium (8-10). Guidelines for monitoring lithium serum levels have been developed worldwide. In the Netherlands, for example, it is recommended to measure lithium serum levels at a frequency of two to four times a year after stable

European Psychiatry, 1998

Pharmacology & Toxicology, 2002

We report a case of a 39-year-old male with bipolar affective disorder who was admitted to hospital with an intentional acute lithium intoxication resulting in renal insufficiency. The patient had previously been treated with lithium, risperidone, fluoxetine and lorazepam, and successfully titrated to lithium levels of 0.7 mmol/l. After overdosing, the lithium level was 5.89 mmol/l and haemodialysis was initiated. A full pharmacokinetic time profile of lithium was obtained. After successful haemodialysis treatment, lithium levels recovered below toxic levels of 1.5 mmol/l in 53 hr. Without intervention non-toxic levels were not expected to have been reached within 6 days, based on computer simulation of predialysis levels. The patient was discharged 6 days after admission without residual symptoms. It was concluded that the lithium intoxication resulted from a combination of lithium overdose and subsequent renal insufficiency due to the overdose. A possible fluoxetine-risperidone interaction was not considered clinically apparent.

Toxicological Sciences, 2014

Lithium-induced neurotoxicity may be life-threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg-Li 2 CO 3 in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg-Li 2 CO 3 in rats receiving 800 mg/l-Li 2 CO 3 in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg-Li 2 CO 3 during 5 days in rats with 15 mg/kg-K 2 Cr 2 O 7 -induced renal failure). Delayed absorption (4.03 vs. 0.31 h), increased plasma elimination (0.65 vs. 0.37 l/kg/h) and shorter half-life (1.75 vs. 2.68 h) were observed in acute-on-chronically compared to acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-thecurve of brain concentrations (379±41 vs. 295±26, P<0.05) and brain-to-plasma ratio (45±10 vs. 8±2, P<0.0001) at 54h]. Moreover, brain lithium distribution was increased in chronically compared to acute-on-chronically poisoned rats (brain-to-plasma ratio: 9±1 vs. 3±0, P<0.01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns.

Psychiatry Research, 2002

Lithium concentrations in plasma of lithium-treated psychiatric patients in the Netherlands: commentary on Cusin et al.