Managing polyuria during lithium treatment: a preliminary prospective observational study

Objectives: Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients. Methods: This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride. Results: Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues. Conclusions: Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.

THE ESTIMATION OF PHARMACOKINETIC PARAMETERS AND ACCURACY OF THE PREDICTED EQUATION FOR LITHIUM DOSE IN CHILDREN: A PILOT STUDY AT THE YUWAPRASART WAITHAYOPATHUM CHILD PSYCHIATRIC HOSPITAL

Objective: The purpose of the study was to estimate the pharmacokinetic parameters and calculate the precision (%RMSE) of the predicted lithium concentration equation.Methods: This research was studied from blood Lithium levels of Children who had visited Yuwaprasart Waithayopathum Child Psychiatric Hospital from 31 December 2009-1 January 2011 The accuracy and precision of the equation were evaluated by the mathematical principle. The assist package software (WIN-NONLIN) was used to create pharmacokinetic parameters.Results: Twenty-nine patients were recruited. The characteristics (mean+SD) presented as the following; age = 15.79+2.64 y, weight = 69.75+22.28 kg and the daily dose = 858.62+274.53 mg. The trough Lithium concentrations (mean+SD) = 0.56+19 mg/l. The kinetic parameter (Mean+SD) presented as the following; t1/2 =7.23+3.38 hr., ke =0.12+0.07 hr-1, Vd = 48.83+15.60 L, AUC0-12 =11.01+5.61 mg x hr/l. The population pharmacokinetic parameters; ke, and AUC (0-∞) = 0.151 hr-1 and 169.81, mg x hr./l respectively. The modified equation from Yukawa for lithium clearance calculation and prediction lithium concentrations were CL (mL/min) = [36.5+(0.242x BW (kg)-7.79]/Scr (mg/dL) and lithium concentration (mg/l) = 4 x Dose (mg)/CL (mL/min)x73.89, respectively with 6.39 %RMSE (test for 20 patients data).Conclusion: In conclusion, the modified Yukawa equation may be used for the prediction of lithium concentration with 6.39% RMSE.

Lithium dosing strategies during pregnancy and the postpartum period

BackgroundLithium is challenging to dose during pregnancy.AimsTo provide guidance for dosing lithium during pregnancy.MethodRetrospective observational cohort study. Data on lithium blood level measurements (n = 1101), the daily lithium dose, dosing alterations/frequency and creatinine blood levels were obtained from 113 pregnancies of women receiving lithium treatment during pregnancy and the postpartum period.ResultsLithium blood levels decreased in the first trimester (−24%, 95% CI −15 to −35), reached a nadir in the second trimester (−36%, 95% CI −27 to −47), increased in the third trimester (−21%, 95% CI −13 to −30) and were still slightly increased postpartum (+9%, 95% CI +2 to +15). Delivery itself was not associated with an acute change in lithium and creatinine blood levels.ConclusionsWe recommend close monitoring of lithium blood levels until 34 weeks of pregnancy, then weekly until delivery and twice weekly for the first 2 weeks postpartum. We suggest creatinine blood levels are measured to monitor renal clearance.

Stutter Exacerbated by Lithium in a Pediatric Patient with Bipolar Disorder

Objective: To report the first known case of a lithium-exacerbated stutter in a pediatric patient. Case Summary: A 10-year-old male with a history of developmental stuttering, bipolar disorder not otherwise specified (NOS), attention-deficit/hyperactivity disorder, and conduct disorder was admitted to the psychiatric hospital because of recurrent suicidal ideations and increased physical aggression toward staff at his residential facility. The patient was being treated with lithium at initial dose of 150 mg/day at bedtime for bipolar disorder NOS. When the lithium dose was increased to 900 mg twice daily to better control the bipolar symptoms, his developmental stutter worsened intensely. When the lithium dose was reduced to 60 mg in the morning and 900 mg at night, the stutter returned to baseline. No other medication changes were made during this interval. His serum lithium concentration was 0.62 mEq/L at baseline, 1.24 mEq/L during the height of his exacerbated stutter, and returned to 0.64 mEq/L after dose reduction. Discussion: To our knowledge, only 1 case lithium-exacerbated stutter has been reported to the literature, and this was in an adult. The developmental stutter of our pediatric patient worsened when he was treated with higher doses of lithium. He was on stable doses of his other medications during the adjustments to the lithium dose, malding it less likely that the stutter was due to one of these medications. However, it is possible that the exacerbation involved an interaction between lithium and one or several of the other medications. Based on the Naranjo probability scale, this case represents a probable adverse drug reaction. Conclusions: Clinicians should be aware that an additional adverse effect of lithium may be an exacerbation of stutter.

Staying at the crossroads: assessment of the potential of serum lithium monitoring in predicting an ideal lithium dose

OBJECTIVE: Lithium has been successfully employed to treat bipolar disorder for decades, and recently, was shown to attenuate the symptoms of other pathologies such as Alzheimer's disease, Down's syndrome, ischemic processes, and glutamate-mediated excitotoxicity. However, lithium's narrow therapeutic range limits its broader use. Therefore, the development of methods to better predict its dose becomes essential to an ideal therapy. METHOD: the performance of adult Wistar rats was evaluated at the open field and elevated plus maze after a six weeks treatment with chow supplemented with 0.255%, or 0.383% of lithium chloride, or normal feed. Thereafter, blood samples were collected to measure the serum lithium concentration. RESULTS: Animals fed with 0.255% lithium chloride supplemented chow presented a higher rearing frequency at the open field, and higher frequency of arms entrance at the elevated plus maze than animals fed with a 50% higher lithium dose presented. Nevertheless, both groups presented similar lithium plasmatic concentration. DISCUSSION: different behaviors induced by both lithium doses suggest that these animals had different lithium distribution in their brains that was not detected by lithium serum measurement. CONCLUSION: serum lithium concentration measurements do not seem to provide sufficient precision to support its use as predictive of behaviors.