Blood Lithium Levels Research Articles

The effect of prenatal lithium exposure on the neuropsychological development of the child.

ObjectivesLithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium‐exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium‐exposed children with the aim to provide further knowledge on the long‐term effects of lithium use during pregnancy.MethodsParticipants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6–14 years. In total, 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders‐Oomen Nonverbal Intelligence Test and the NEPSY‐II‐NL assessment. Linear and negative binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated.ResultsLithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population.ConclusionIn this study, we found no evidence for significantly altered neuropsychological functioning of lithium‐exposed children at the age of 6–14 years, when compared to non‐lithium‐exposed controls.

Lithium placental passage at delivery and neonatal outcomes: A retrospective observational study

Introduction Lithium is an effective mood stabilizer and is widely used as a first-line treatment for bipolar disorder in the perinatal period. Several guidelines have provided clinical advice on dosing strategy (dose reduction versus stop lithium) in the peripartum period to minimize the risk of neonatal complications. An association has been observed between high neonatal lithium concentrations (> 0.64 mEq/L) and lower 1-min Apgar scores, longer hospital stays, and central nervous system and neuromuscular complications.ObjectivesTo quantify the rate of lithium placental passage at delivery. To assess any association between plasma concentration of lithium at delivery and neonatal outcome.Methods In this retrospective observational cohort study, we included women treated with llithium at least in late pregnancy. Maternal (MB) and umbilical cord (UC) lithium blood level measurement were collected at delivery. Lithium serum concentrations were determined by means of an AVL 9180 electrolyte analyzer. The limit of quantification (LoQ) was 0.20 mEq/L and detection limit was 0.10 mEq/L. From the medical records, we extracted information on neonatal outcomes (preterm birth, birth weight, Apgar scores, pH-values, and admision to NICU) and complications categoriced by organ system: respiratory, circulatory, hematological, gastro-intestinal, metabolic, neurological, and immune system (infections).ResultsUmbilical cord and maternal lithium blood levels were strongly correlated: mean (SD) range UC/MR ratio 1.15 (0.24). Umbilical cord lithium levels ranged between 0.20 to 1.42 mEq/L. We observed no associations between umbilical cord lithium blood levels at delivery and neonatal outcomes.ConclusionsIn our study, newborns tolerated well a wide range of lithemias, between 0.20 and 1.42 mEq/L.

Lithium Prescribing and Therapeutic Drug Monitoring in Bipolar Disorder: A Survey of Current Practices and Perspectives.

The goal of this survey study was to assess specific aspects of lithium therapy for bipolar disorder, including psychiatrists' prescribing practices, understanding of therapeutic drug monitoring, and concerns and perspectives regarding lithium therapy. A 14-item survey was electronically distributed to 225 staff psychiatrists at 8 academic hospitals. The survey was completed by 85 psychiatrists (38% of the 225 psychiatrists to whom the survey was distributed), with between 81 and 85 respondents completing the different items. When asked about the agents with which they initiated therapy, 49 (61%) reported initiating therapy with an atypical antipsychotic and 34 (42%) reported starting with lithium therapy in 50% or more of patients newly diagnosed with bipolar disorder. When prescribing lithium, most of the respondents (n=68, 82%) reported that they used once daily dosing, and 67 respondents (79%) indicated that they ordered lithium blood levels 12 hours postdose. When interpreting lithium levels, 46 respondents (55%) reported "always" changing a clinically stable patient's lithium dose when the level was above the therapeutic range, compared with 4 (5%) who reported always changing the dose when the level was below the therapeutic range. When asked about their concerns regarding lithium therapy, more than half of the respondents reported that they were especially concerned about toxicity, organ dysfunction, and other adverse effects, as well as therapeutic drug monitoring. Shifts in prescribing practices, inconsistent interpretation of lithium levels, and concerns about safety and therapeutic drug monitoring highlight the need for evidence-informed guidelines reflective of current practice.

Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates.

Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25–82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m2). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.

Management of lithium dosing around delivery: An observational study.

ObjectivesRecommendations on lithium dosing around delivery vary, with several guidelines suggesting that lithium should be discontinued prior to delivery. We aimed to evaluate the validity of these recommendations by investigating 1) maternal lithium blood level changes following delivery, and 2) the association between neonatal lithium blood levels at delivery and neonatal outcomes.MethodsIn this retrospective observational cohort study, we included women with at least one lithium blood level measurement during the final week of pregnancy and the first postpartum week. For aim 2, we included a subcohort of women with neonates for whom neonatal lithium blood levels (obtained from the umbilical cord or a neonatal vein puncture within 24 hours of delivery) were available.ResultsThere were a total of 233 maternal lithium blood level measurements; 55 (23.6%) in the week before delivery and 178 (76.4%) in the week after. There was no association between time and lithium blood level/dose ratio (Pearson correlation coefficient −0.03, P = .63). Additionally, we included a total of 29 neonates for whom a lithium measurement was performed within 24 hours postpartum. Maternal and neonatal lithium blood levels were strongly correlated. We observed no associations between neonatal lithium blood levels at delivery and neonatal outcomes.ConclusionBased on our findings, we do not recommend lowering the dosage or discontinuation of lithium prior to delivery. Stable dosing can prevent subtherapeutic lithium serum levels, which is especially important in the postpartum period when relapse risks are highest.

SO081LITHIUM EXPOSURE AND OCCURENCE OF CHRONIC KIDNEY DISEASE IN THE IRISH HEALTH SYSTEM: A COHORT STUDY

Abstract Background and Aims Lithium is implicated as a causative factor in the development and progression of chronic kidney disease (CKD). Few studies have assessed the independent impact of plasma levels and duration of lithium therapy on CKD progression. We examined the influence of lithium on CKD progression in the Irish health system. Method We utilised data from the Irish Kidney Disease Surveillance System (IKDSS) to explore associations of lithium levels and duration of exposure with kidney function in a regional cohort. A retrospective cohort study was conducted between 1999 to 2014 from the Midwest Region. All adult patients with lithium levels were identified and followed longitudinally. Kidney function was assessed at baseline and longitudinally using serum creatinine and estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI. Patients with &amp;lt; 2 lithium values, missing data on creatinine were excluded. The index date was the date of the first lithium blood test. Toxicity from lithium was defined as levels &amp;gt;1.2mmol/L as per NICE guidelines while duration of treatment was calculated based on patient –years of exposure as determined by positive blood lithium levels. Relationships between baseline kidney function, lithium levels, duration of exposure and each patients most recent eGFR value on follow up were assessed using multiple linear regression Results We identified 1,978 patients exposed to lithium from 1999-2014, mean age was 47.4 (15.6), 45.1% were men, eGFR [median (IQR)] at baseline was 84.4 (32.1) ml/min1.73m and the median duration of exposure was 3.0 years (IQR=4 years). Frequency of lithium testing increased from 1.77 in 1999 to 2.66 in 2014. In multiple linear regression, the final eGFR on follow-up was significantly lower in older patients (-0.48 ml/min/1.73m per year increase in age), P&amp;lt;0.001; in patients with elevated baseline lithium levels (-2.18 ml/min1.73m lower per unit increase), P&amp;lt;0.05, with long duration of exposure (-1.42 ml/min/1.73m lower for each year on lithium), P&amp;lt;0.001, and for patients with low GFR at baseline (P&amp;lt;0.001). Together these variables explained 58% of the variation in the final model. Conclusion Both the magnitude of and the duration of lithium exposure are both independently associated with CKD progression among lithium users in the Irish health system. Higher baseline lithium values had a more deleterious impact on kidney function. Continued efforts should be expended in minimising the risks of lithium induced nephrotoxicity through switching to alternatives and dose reduction when over possible. Funding This study is funded by the Health Research Board and the Midwest Research and Education Foundation (MKid).

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.

Methodology for rapid assessment of blood lithium levels in ultramicro volumes of blood plasma for applications in personal monitoring of patients with bipolar mood disorder.

Bipolar disorder (BD) is a common mental health condition, characterized by extreme changes in mood, energy, and behavior. BD is often managed through mood-stabilizing medications, of which lithium formulations remain the most reliable and effective at reducing the risk of suicide. To achieve adequate and consistent efficacy, lithium concentrations need to be maintained within a narrow therapeutic range (0.4 to 1.2 mmol / L). Because of its narrow therapeutic index, long-term lithium therapy is associated with serious side effects and risks of toxicity. It is believed that the availability of a personal blood lithium analyzer would benefit patients who are on lithium treatment. We detail the results of a spectrophotometric method performed on ultramicro volumes to determine blood plasma lithium concentrations as compared with reference measurements of flame photometry, and validated in samples of unknown lithium content. Applying multiple linear regression, lithium concentrations could be determined in a rapid manner using full-range spectra or triwavelength data. Both techniques highly correlated with reference standards and could predict lithium levels accurately (R2 = 0.794214 and RMSEP = 0.209584, and R2 = 0.863921 and RMSEP = 0.167524, respectively). Therefore, this method can be a useful for rapid assessment of blood lithium in nonlaboratory settings i.e., general practices, hospital clinics, and community health centers by healthcare professionals and/or by patients. Future work will now focus on completion of a miniaturized and integrated system that will deliver a portable and personal lithium-monitoring device.

Lithium treatment in bipolar adolescents: a follow-up naturalistic study.

BackgroundAlthough lithium is currently approved for the treatment of bipolar disorders in youth, long term data, are still scant. The aim of this study was to describe the safety and efficacy of lithium in referred bipolar adolescents, who were followed up at the 4th (T1) and 8th (T2) month of treatment.MethodsThe design was naturalistic and retrospective, based on a clinical database, including 30 patients (18 males, mean age 14.2±2.1 years).ResultsMean blood level of lithium was 0.69±0.20 mEq/L at T1 and 0.70±0.18 mEq/L at T2. Both Clinical Global Impression-Severity (CGI-S) and Children Global Assessment Scale (C-GAS) scores improved from baseline (CGI-S 5.7±0.5, C-GAS 35.1±3.7) to T1 (CGI-S 4.2±0.70, C-GAS 46.4±6.5; P<0.001), without significant differences from T1 to T2. Thyroid-stimulating hormone significantly increased from 2.16±1.8 mU/mL at baseline to 3.9±2.7 mU/mL at T2, remaining within the normal range, without changes in T3/T4 levels; two patients needed a thyroid hormone supplementation. Creatinine blood level did not change. No cardiac symptoms and electrocardiogram QTc changes occurred. White blood cell count significantly increased from 6.93±1.68 103/mmc at baseline to 7.94±1.94 103/mmc at T2, and serum calcium significantly increased from 9.68±0.3 mg/dL at baseline to 9.97±0.29 mg/dL at T2, both remaining within the normal range; all the other electrolyte levels were stable and normal during the follow-up. The treatment with lithium was well tolerated, probably due to the relatively low lithium blood levels. Gastrointestinal symptoms (16.7%), sedation (9.7%) and tremor (6.4%) were the most frequently reported side effects.ConclusionLithium was effective and safe in adolescent bipolar patients followed-up for eight months.

THE STATE OF BONE METABOLISM IN LUNG CANCER PATIENTS

Patients underwent dual-energy X-ray osteodensitometry of proximal part of femoral bone. Osteopontin (OP), osteocalcin (OC) and alkaline phosphatase (AP) parameters were studied in blood, as well as osteo-associated chemical elements. Lung cancer proceeds with severe disorders of bone metabolism, which is accompanied by an increase in blood levels of OP, OС, AP, phosphorus, lithium, lead, strontium and cobalt against a decrease of calcium, magnesium and manganese, which were observed in 75; 78; 31; 100; 66; 47; 44; 3; 100; 100, and 6% of patients, respectively; such disorder was associated with a morphological variant of the tumor (cobalt) and stage of disease (calcium, magnesium, manganese, strontium), development of osteodeficit (OP, OC, AR, strontium, zinc). Osteodeficit in the form of osteopenia and osteoporosis is observed more common in women, in every second patient, and osteodensimetric T-score depends on the age of patients, directly correlates with the values of the OP and OC, and inversely- with a zincemia rate. The disorders of bone metabolism in patients with lung cancer indicate the need for the development of antiosteoporosis treatment for cancer patients.

A Method for Rapid, Reliable, and Low-Volume Measurement of Lithium in Blood for Use in Bipolar Disorder Treatment Management.

Lithium preparations are considered the most reliable mood stabilizers for patients with Bipolar Disorder (BD), and are the most effective at reducing the risk of suicide. However, maintaining blood lithium concentration within the narrow therapeutic range of 0.4-1.2 mEq is crucial but extremely difficult. The aim of this work is to develop a personal lithium blood level analyzer using a novel method of combined optical and electrical impedance spectroscopy to test micro volumes of spiked samples of human blood. Impedance measurements alone showed a limit of detection of less than 0.1mEq within the therapeutic range, whereas optical measurements could verify the presence of lithium and provide a degree of lithium content. Optical specificity to lithium was further verified in qualitative assessment of lithium spiked blood samples with varying concentrations of sodium. Moreover, analysis of multiple linear regression yielded a prediction model of R2 = 0.322716 and RMSEP = 0.223602 for optical measurements only using feature wavelengths, which were found to appear at minima 560 and 605nm. Combined with impedance measurements, prediction of lithium concentration in samples with unknown lithium content was significantly increased to R2 = 0.876438 and RMSEP = 0.513554. The combination of optical and impedance modalities for determinations of blood lithium resulted in significant improvement to the sensitivity and accuracy of measurement. Results are complementary of the proposed opto-impedance method, and future work will now focus on the technical development of an integrated and miniaturized system for measurement of lithium levels in blood with a high level of accuracy and sensitivity.

Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice.

Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy. Twelve-week old female BTBR-ob/ob mice were treated for 12 weeks with 0, 10 and 40 mmol LiCl/kg after which the development of diabetes and diabetic nephropathy were analysed. In comparison to BTBR-WT mice, ob/ob mice demonstrated elevated bodyweight, increased blood glucose/insulin levels, urinary albumin and immunoglobulin G levels, glomerulosclerosis, reduced nephrin abundance and a damaged proximal tubule brush border. The lithium-10 and -40 diets did not affect body weight and resulted in blood lithium levels of respectively <0.25 mM and 0.48 mM. The Li-40 diet fully rescued the elevated non-fasting blood glucose levels. Importantly, glomerular filtration rate was not affected by lithium, while urine albumin and immunoglobulin G content were further elevated. While lithium did not worsen the glomerulosclerosis, proximal tubule function seemed affected by lithium, as urinary NGAL levels were significantly increased. These results demonstrate that lithium attenuates non-fasting blood glucose levels in diabetic mice, but aggravates urinary albumin and immunoglobulin G content, possibly resulting from proximal tubule dysfunction.

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.

Profile of lithium carbonate use in patients with bipolar disorder in Colombia

Lithium is the drug of choice for the treatment of bipolar affective disorder. To define lithium therapeutic profile and adverse reactions to its use in patients with bipolar affective disorder in Colombia. We conducted an observational retrospective cohort study between January 1 and December 31, 2013, which included patients with a diagnosis of bipolar disorder treated with lithium carbonate in 25 Colombian cities; we evaluated socio-demographic variables, lithium dose, co-medication, drug interactions and adverse reactions. A multivariate analysis was done using SPSS 22.0. The 331 patients had an average age of 44.5 ± 13.9 years; 59.2% were women. The mean dose of lithium was 898 ± 294 mg/day; 22% received doses lower than recommended, and patients had received lithium for 38.0 ± 39.5 months (range: 12-159 months). Lithium levels in blood had been measured only in 13.5% of patients; 71.3% of them had received adjuvant therapy for bipolar disorder with other drugs, especially clozapine (16.6%) and valproic acid (16.6%). The main comorbidities were hypothyroidism (18.1%) and hypertension (12.7%); 390 potentially toxic drug interactions were found, and adverse reactions were reported in 1.2% of patients. A statistically significant association was found between a lower risk of combination therapy and receiving treatment in the cities of Bogotá (OR=0.4, p=0.025), Cartagena (OR=0.3, p=0.015) and Ibagué (OR=0.3, p=0.025). Lithium was generally used at recommended doses and intervals, but a significant percentage of patients received lower doses than those recommended, and it was not possible to compare with lithium levels in blood. Adverse reactions and blood lithium levels reporting should be improved in patients with bipolar disorder in Colombia.

Colorimetric determinations of lithium levels in drop-volumes of human plasma for monitoring patients with bipolar mood disorder.

Lithium preparations are considered the most reliable form of mood stabilizing medication for patients with Bipolar disorder. Nevertheless, lithium is a toxic element and its therapeutic range is extremely narrow, with levels of 0.61.0 mEq considered normal, whereas levels above 1.5 mEq are toxic. Thus unfortunately, many patients reach toxic levels that lead to unnecessary complications. It is believed that personal monitoring of blood lithium levels would benefit patients taking lithium medication. Therefore, our aim is to develop a personal lithium blood level analyzer for patients with bipolar mood disorder, and we report here our initial results of a colorimetric-based method used to test drop-volumes of human plasma that had been spiked with lithium. It was possible to validate results with standard flame photometry readings. Applying the Partial Least Squares (PLS) method on preprocessed spectra, therapeutic concentrations of lithium in a single drop can be predicted in a rapid manner, and furthermore, the calibration results were used to select effective wavelengths which were employed as inputs in Multiple Linear Regression (MLR). The simplified algorithms of this would prove useful when developing a personal lithium analyzer. Overall, both calibration methods gave high correlation and small error outputs with a R2= 0.99036 and RMSEC = 0.03778, and R2= 0.994148 and RMSEC= 0.0294404, for PLS and MLR methods, respectively. The results show that the spectrophotometric determination of blood lithium levels can be extended beyond laboratory applications and indicate the capability of this testing principle to be employed in a personal monitoring device. Future work will now focus on the technical development of a miniaturized system for measurement of lithium levels in blood with an acceptable level of accuracy and sensitivity.

Lurasidone adjunctive with lithium or valproate for bipolar depression: A placebo-controlled trial utilizing prospective and retrospective enrolment cohorts

In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium or valproate, patients with bipolar I depression were randomized to 6 weeks of double-blind treatment with lurasidone (N = 180) or placebo (N = 176), added to background treatment with lithium or valproate. All patients were treated with lithium or valproate for a minimum of 4 weeks prior to screening. This was confirmed either by prospective treatment after study enrolment (run-in cohort), or retrospectively, with blood levels of lithium and valproate at screening (non-run-in cohort). Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP-S), respectively. Treatment with lurasidone was associated with non-significant improvement at week 6 vs. placebo for the MADRS total score (−11.8 vs −10.4; P = 0.176), and the CGI-BP-S score (−1.36 vs −1.13; P = 0.095). Significant separation from placebo was observed from weeks 2–5 for the MADRS and weeks 3–5 for the CGI-BP-S. Improvement in the placebo-subtracted MADRS total score was notably larger at week 6 for the non-run-in cohort compared to the run-in cohort (LS mean difference in endpoint change scores, −4.6; P = 0.009). Adverse events most frequently reported for lurasidone were akathisia, somnolence, and extrapyramidal side effects. In conclusion, lurasidone adjunctive with lithium or valproate demonstrated significant improvement in depressive symptoms based on the MADRS from weeks 2–5 but not at the primary week 6 endpoint.

Asystolie perstimulus résultant d’une hypertonie parasympathique au cours des électroconvulsivothérapies : cas clinique, brève revue de la littérature et discussion

Electroconvulsive therapy (ECT) is most frequently indicated for episodes of melancholic depression, but is also useful in the treatment of maniac syndrome and some schizophrenia subtypes. ECT is part of the treatment of movement disorders, neuroleptic malignant syndrome and even in the treatment of severe conversions. Although the therapeutic results are excellent when used appropriately, the mortality rate is estimated between 2and 4for 100,000shocks. Despite this mortality rate, the benefit-risk ratio remains very positive and serious complications are extremely rare. ECT results in a biphasic cardiological effect: firstly a perstimulus parasympathetic hypertonia contemporary to the seizure's tonic phase, then a phase of contemporary sympathetic hypertonia during the epileptic clonic movement. We will focus on the perstimulus asystole as it is by far the most frequent. Very few cases and even less studies have been referenced in the literature; here, we present a clinical case followed by a discussion. The patient is in his fifties and has been treated for many years for a unipolar mood disorder with recurrent melancholic depressive episodes. With each new depressive episode, the clinical evolution is rapidly positive after a few sessions of ECT. Maintenance ECT was not retained due to the supra-annual periodicity of the melancholic depressive episodes and rapid recovery after electric treatment. Then, this patient developed another depressive decline in mood comparable to the previous one, despite adapted blood lithium levels associated with a new generation antidepressant treatment. According to his history, a hospitalisation was programmed to carry out a new course of ECT. Considering the short duration of the first seizures, the intensity of the stimulus was progressively increased. At 180joules, the patient presented an immediate per-stimulus asystole of 20seconds which ceased spontaneously. The specialized cardiologic consultation following the rhythmic episode was reassuring: the patient's cardiac condition remained stable. However, after discussion with the patient and his family, we decided to stop the ECT. Was this a reasonable decision? According to the literature, the patient's medical history, sex, psychiatric diagnosis, the shock parameters (level of energy applied, duration of the stimulus, number of shocks) and clinical results, are not predictive factors in the occurrence of an asystole. Concerning the ECT protocol, the vagus nerve seems less stimulated during bifrontal stimulations in opposition to unilateral stimulations. Perasystolic patients are younger and have less prior history of cardiovascular disease or ECG abnormalities. Although the patients receiving ECT are often taking several medications (antipsychotics, benzodiazepines, antidepressants, anticholinergic correctors, calcium channel blockers, loop diuretics, converting enzyme inhibitors), these drugs are not considered as facilitating asystoles. No increase in the frequency of asystole had been observed when taking an average dose psychotropic treatment allowing the continuation of an antidepressant treatment at the recommended dose. Differently, lithium is regularly stopped during the shock phase as it could -even a few days after being stopped- potentiate the effects of succinylcholine and increase the vagal tone. Succinylcholine seems to promote asystole, whilst caffeine, methohexital and trimethaphan do not. The hypersympathetic phase can be controlled by a betablocker (propranolol, esmolol, labetalol) that does not increase the prior risk of asystole. Anticholinergic premedication using atropine does not appear to be systematic and could even potentially induce tachy-dysarrhythmia. However, in the case of perstimulus asystole, most authors recommend continuing the shocks with doses of atropine around 0.4to 1mg. Vagal stimulation is preferentially central and directly linked to the electric excitation of the lateral dorsal motor nucleus of the vagus nerve. Younger patients with no cardiac history are more at risk. This could be explained by the fact that juvenile tissue conducts electricity more rapidly than senescent (the difference being probably due to the fibrosis and adipose tissue which reduce its conductive capacity). Finally, it is appropriate to question the direct therapeutic aspect of vagal stimulation which constitutes an experimental treatment of resistant depression. The occurrence of perstimulus asystole is not considered as a serious complication of ECT and therefore as a contra-indication to any future sessions. On the contrary, most authors are campaigning for the continuation of shocks with the possibility of adding prophylactic intravenous atropine. Cardiac arrest reminds us that ECT requires a special attention to its cardiovascular effect, which emphasizes the role of interdisciplinarity between anaesthesiologists and psychiatrists.

A case of hypomania with low-dose lamotrigine

Byline: Serap. Oflaz, Eren. Y?ld?zhan, Zeynep. Tatar, Fatma. Akyuz Sir, Lamotrigine is an effective treatment for acute bipolar depression. [sup][1] Although a recent review concluded that the lamotrigine does not increase the incidence of hypomania or manic switches, [sup][2] cases of lamotrigine-induced manic switches in patients with bipolar disorder have been reported. [sup][3],[4] We would like to report a case of hypomanic switches with low doses of lamotrigine. A 42-year-old man was referred to our outpatient clinic because of unhappiness and fatigue since more than a year. He had a 19-year history of bipolar disorder that included three psychiatric hospitalizations for manic episodes with psychotic features. His manic episodes were preceded by depressive episodes, which dominated his clinical course. He had been taking lithium 1200 mg/day and olanzapine 2.5 mg/day regularly as a mood stabilizer for more than 2 years. He had previously taken fluoxetine and bupropion for depression, but they were not effective in relieving his depressive symptoms. The patient had complained of weight gain during follow-up; therefore, olanzapine was discontinued. Lamotrigine 25 mg/day was added at bedtime and increased by 25 mg after 2 weeks. However, after 2 weeks, he reported restlessness, decreased need for sleep (5 h/day), improved mood, increased energy, and distractibility. As a result, the dose was reduced to 25 mg/day, which led to amelioration of the hypomanic symptoms. After 2 weeks, his depressive symptoms re-emerged, and he was prescribed lamotrigine 37.5 mg/day. After 1 week, he complained of the same hypomanic symptoms. A diagnosis of hypomania (lamotrigine induced) was made, and the dose was again decreased to 25 mg/day; his symptoms subsequently improved over 2 weeks. He was regularly taking prophylactic lithium during follow-up, and although his blood lithium level was in the therapeutic range (0.89 mEq/L), he experienced lamotrigine-induced hypomania. Lithium 1200 mg/day and lamotrigine 25 mg/day were continued during the follow-up, and he remained stable without the recurrence of hypomania or depression for approximately 1 year. The temporal correlations between the occurrence of hypomania and increases in lamotrigine doses (37.5 mg and 50 mg) and those between the disappearance of hypomania and decreases in lamotrigine doses (25 mg) suggest that the patient's hypomania was induced by lamotrigine. …

Minimizing negative outcomes associated with potentially harmful lithium levels by means of pharmacist-led educational interventions in an inpatient psychiatric facility

Introduction: Studies examining educational interventions led by pharmacists to minimize negative outcomes associated with elevated and potentially harmful lithium levels in inpatient psychiatric facilities are lacking. Other studies indicate a need for improvement of therapeutic drug monitoring for lithium. The aim of this article is to identify potential improvements in negative outcomes associated with harmful lithium blood levels after educational interventions are delivered by a clinical pharmacist to providers of an inpatient psychiatric facility. Methods: Medication reports were queried from the pharmacy database to identify all patients who were taking lithium within 1 year. Laboratory results, physician progress notes, nursing progress notes, and treatment plans were studied to detect any adverse events associated with lithium levels. Educational interventions created by pharmacy services were tailored toward medical staff and delivered over a 3 month period. Learning was assessed at pre-educational and posteducational interventions. Results: One hundred fifteen patients received lithium between March 2012 and March 2013. The most-frequent adverse effects reported associated with lithium included tremor, dizziness, slurred speech, and lethargy. Two patients were sent to the local emergency department for lithium toxicity and required dialysis. Fifty-two patients received lithium after educational interventions, and no adverse events were reported. A lithium drug-monitoring spreadsheet was created for pharmacy use, and drug-monitoring guidelines were revised and disseminated throughout the facility. Discussion: A reduction in negative outcomes associated with lithium was noted after educational interventions to medical staff occurred. The impact of pharmacist-led educational interventions demonstrated a high potential for success.

Why lithium studies for ALS treatment should not be halted prematurely

GENERAL COMMENTARY article Front. Neurosci., 02 September 2014Sec. Neuropharmacology Volume 8 - 2014 | https://doi.org/10.3389/fnins.2014.00267