lithium-chloride and Drug-Overdose

Lithium (Li) is a first-line treatment for bipolar disorder but has a narrow therapeutic index. Treatment of Li toxicity includes supportive measures and hemodialysis in severe cases, but this modality is not always immediately available. Sodium polystyrene sulfonate (SPS, Kayexalate), a cation exchanger, has been promising in animal models and human reports to reduce absorption and enhance elimination of Li.. A retrospective cohort study was conducted. All cases of chronic Li intoxication were reviewed in two adult-care hospitals from 2000 to 2009. A group comparison and a within-patient comparison were performed to compare the effect of SPS on the median Li half-life (T(1/2)). For this study, at least three serum Li levels were required for T(1/2) calculations.. Forty-eight patients met inclusion requirements, 12 of whom had taken SPS. Median Li T(1/2) in the treated and control groups was 20.5 and 43.2 hours, respectively (p = 0.0006). In the 12 treated patients, Li T(1/2) during SPS was on average 48.9% shorter than without SPS. Furthermore, in one subject in whom urinary Li data were available, Li clearance with SPS was superior to Li renal clearance. Prolonged constipation was noted in one patient whereas mild hypokalemia was noted in six patients treated with SPS.. This study shows that SPS reduced Li T(1/2) and suggests that SPS is capable of promoting Li elimination in chronic intoxications. These results warrant a prospective trial looking at the use of SPS in the treatment of Li overdose as an adjunct to supportive measures and hemodialysis.

Topics: Adult; Aged; Algorithms; Antidotes; Antimanic Agents; Area Under Curve; Cohort Studies; Drug Overdose; Female; Half-Life; Humans; Lithium Chloride; Male; Middle Aged; Poisoning; Polystyrenes; Retrospective Studies

The safety of antidepressants following overdose is critical because of the high risk of suicide attempts in depressed patients. This study was conducted to decrease the fatality rate of antidepressant overdoses by providing data to shift prescribing toward safer antidepressants.. US poison control data for 2000-2004 were analyzed by 25 antidepressant types. Medical outcome differences were quantified using a hazard index (number of major or fatal outcomes per 1000 reported antidepressant ingestions).. Of 82,802 suicidal single-agent ingestions of identifiable antidepressants approved for use in the US, cases occurred predominantly in females and peaked in teens. Fatal cases peaked at 40 to 49 years of age. Suicidal ingestions of the SSRIs, SNRIs, and other antidepressants peaked in teens, lithium in the twenties, tricyclics and tetracyclics in the thirties, and MAO inhibitors in the forties. There were 40 major or fatal outcomes per 1000 cases. Weighted by antidepressant type, the mean hazard index for the 25 antidepressants was 79 (range: 0 to 292). Amoxapine (292), maprotiline (211), and desipramine (187) had the highest hazard indices. The tricyclic antidepressants, MAO inhibitors, maprotiline, and bupropion were in the more severe half of antidepressants, ranked by hazard index. All SSRIs had low hazard indices. Hazard index and exposure frequency were inversely correlated (R = -0.423, p = 0.035), while hazard index and use of critical care were positively correlated for the 25 antidepressant types (R = 0.797, p < 0.001). Clinical effect profiles for each antidepressant type are presented.. Suicidal overdose severity varied considerably by antidepressant type. Prescribing decisions should be informed by regularly updated comparative overdose severity data.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Adult; Age Factors; Aged; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antimanic Agents; Child; Drug Overdose; Female; Humans; Lithium Chloride; Male; Middle Aged; Monoamine Oxidase Inhibitors; Selective Serotonin Reuptake Inhibitors; Sex Factors; Suicide; Suicide, Attempted; Treatment Outcome; United States; Young Adult

Previous studies have shown that oral sodium polystyrene sulfonate lowers plasma lithium concentrations after acutely administered oral doses of lithium chloride. However, a significant proportion of lithium overdose cases resulting in morbidity and mortality are those in which exposure to lithium is chronic. This study was designed to determine whether multiple oral doses of sodium polystyrene sulfonate are effective in reducing plasma lithium concentrations after chronic dosing.. Placebo-controlled animal study.. One hundred thirty mice were given 75 mM lithium chloride in their drinking water for a period of 14 days. At the end of that period, half of the animals were given orogastric sodium polystyrene sulfonate at 5 g/kg/dose 0, 60, 120, 180, and 360 minutes after the cessation of lithium chloride; the remaining half received orogastric water at equivalent times. Subgroups of each group were sacrificed at 90, 150, 330, 480, 1440, and 2880 minutes after lithium chloride cessation and plasma analyzed for lithium content. Lithium concentrations were compared by analysis of variance and single degree of freedom contrasts. Significance was set at an alpha level of 0.05.. Lithium concentration was lower overall in the animals treated with sodium polystyrene sulfonate (p < .0001) and specifically at 150, 330, and 480 minutes after lithium chloride cessation (p < .05).. Repetitive oral doses of sodium polystyrene sulfonate effectively lowered plasma lithium concentrations. Further study may ultimately define a role for the use of sodium polystyrene sulfonate in the treatment of patients with chronic lithium toxicity.

Topics: Administration, Oral; Animals; Drug Overdose; Lithium; Lithium Chloride; Male; Mice; Poisoning; Polystyrenes; Random Allocation; Treatment Outcome