Electronic health record nested pragmatic randomized controlled trial of a reminder system for serum lithium level monitoring in patients with mood disorder: KONOTORI study protocol.

BACKGROUND: The weaknesses of classical explanatory randomized controlled trials (RCTs) include limited generalizability, high cost, and time burden. Pragmatic RCTs nested within electronic health records (EHRs) can be useful to overcome such limitations. Serum lithium monitoring has often been underutilized in real-world practice in Japan. This trial aims to evaluate the effectiveness of the EHR-nested reminder system for serum lithium level monitoring in the maintenance of therapeutic lithium concentration and in the improvement of the quality of care for patients on lithium maintenance therapy. METHODS: The Kyoto Toyooka nested controlled trial of reminders (KONOTORI trial) is an EHR-nested, parallel-group, superiority, stratified, permuted block-randomized controlled trial. Screening, random allocation, reminder output, and outcome collection will be conducted automatically by the EHR-nested trial program. Patients with a mood disorder taking lithium carbonate for maintenance therapy will be randomly allocated to the two-step reminder system for serum lithium monitoring or to usual care. The primary outcome is the achievement of therapeutic serum lithium concentration between 0.4 and 1.0 mEq/L at 18 months after informed consent. DISCUSSION: The KONOTORI trial uses EHRs to enable the efficient conduct of a pragmatic trial of the reminder system for lithium monitoring. This may contribute to improved quality of care for patients on lithium maintenance therapy. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000033633. Registered on 3 July 2018.

Factors influencing lithium pharmacokinetics in patients with acute mania: A population pharmacokinetic analysis.

OBJECTIVE: The objective of this study was to conduct a population pharmacokinetic model of lithium in Thai patients with acute mania. METHODS: Lithium concentrations from 222 acute manic patients were included in this study. The population pharmacokinetic model was developed using NONMEM 7.3 software. Influences of potential covariates including body size, age, renal function, and gender were evaluated through a stepwise approach. Bootstrap analysis and an external validation approach were used to evaluate the robustness and predictability of the final model. RESULTS: A one-compartment model adequately described lithium pharmacokinetics. Body weight and age were significant predictors for lithium clearance, with the following relationship: CL/F (L/hr) = 1.43 * (WT/65)0.425  * (age/38)-0.242 . The population estimates of lithium clearance, volume of distribution, and absorption rate constant of the final model were 1.43 L/hr, 54 L (fixed), and 0.426 hr-1 (fixed), respectively. Model evaluation showed that the final model was predictive and robust. CONCLUSIONS: A population pharmacokinetic model of lithium with good performance was developed in Thai patients with acute mania. This model can be used to assist clinicians in individualized lithium therapy.

The Combination of Lithium and ACE Inhibitors: Hazardous, Critical, Possible?

Lithium is a well established therapeutic agent in the treatment of uni- and bipolar affective disorders. Angiotensin-converting enzyme (ACE) inhibitors are the most frequently used class of drugs in the treatment of cardiovascular diseases. Combination therapy with both may be considered in clinical practice on occurrence of arterial hypertension after years of successful lithium therapy, yet an increased risk of lithium intoxication in combination with ACE inhibitors has been described and thus the combination has been warned against. We describe three cases in which enalapril, lisinopril or ramipril was combined with lithium. Either additional co-medication with hydrochlorothiazide or dehydration rather than co-medication with ACE inhibitors could be identified as necessary factors for lithium intoxication. These cases suggest that a combination of lithium with ACE inhibitors is possible when sufficient hydration is ensured and a combination with hydrochlorothiazide is avoided. Lithium concentration should be controlled on a regular level.

Population pharmacokinetic modeling of sustained release lithium in the serum, erythrocytes and urine of patients with bipolar disorder.

PURPOSE: Lithium (Li), the first-line treatment of bipolar disorder, was first developed as an immediate-release form with a routine therapeutic drug monitoring 12 h after the last dose. In Europe, the most commonly prescribed form is a sustained release (srLi). Yet no pharmacokinetics (PK) study has been published of srLi, administered once a day, in adults. The present study describes srLi PK in the serum and erythrocytes of bipolar patients. METHODS: To assess srLi PK, we studied prospectively 17 French bipolar patients on a median dose of 1000 mg (600-1600) for at least 2 years. Serum (S), erythrocyte (E) concentrations, and urinary (U) amount were collected over 8 h after 15 days of morning intake using monitoring electronic medical system (MEMs). Population PK parameters were estimated using the SAEM algorithm (MONOLIX 4.3.3 software). RESULTS: Using a population approach, we built a PK population model of srLi including one S compartment (VS = 23.0 L, ClS = 1.21 L h-1), one E compartment (VE = 64.7 L, ClSE = 3.63 L h-1, ClES = 9.46 L h-1), and one U compartment (F = 0.62) and estimate the ratio of concentrations to Li in E over S at 0.38 with 27% between-subject variability. CONCLUSION: This is a PK model of srLi once a day in bipolar patients using a population approach simultaneously describing Li concentrations in serum, erythrocytes, and urine which provide an estimate of the ratio of concentration in erythrocyte over serum and its between-subject variability (BSV).

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

GOAL: 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. RESULTS: Impedance measurements alone showed a limit of detection of less than 0.1 mEq 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 605 nm. 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. CONCLUSION: The combination of optical and impedance modalities for determinations of blood lithium resulted in significant improvement to the sensitivity and accuracy of measurement. SIGNIFICANCE: 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.

LISPRO mitigates ß-amyloid and associated pathologies in Alzheimer's mice.

Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3). We found that LISPRO (8-week oral treatment) reduces ß-amyloid plaques and phosphorylation of tau by reducing neuroinflammation and inactivating glycogen synthase kinase 3ß in transgenic Tg2576 mice. Specifically, cytokine profiles from the brain, plasma, and splenocytes suggested that 8-week oral treatment with LISPRO downregulates pro-inflammatory cytokines, upregulates anti-inflammatory cytokines, and suppresses renal cyclooxygenase 2 expression in transgenic Tg2576 mice. Pharmacokinetic studies indicated that LISPRO provides significantly higher brain lithium levels and more steady plasma lithium levels in both B6129SF2/J (2-week oral treatment) and transgenic Tg2576 (8-week oral treatment) mice compared with Li2CO3. Oral administration of LISPRO for 28 weeks significantly reduced ß-amyloid plaques and tau-phosphorylation. In addition, LISPRO significantly elevated pre-synaptic (synaptophysin) and post-synaptic protein (post synaptic density protein 95) expression in brains from transgenic 3XTg-AD mice. Taken together, our data suggest that LISPRO may be a superior form of lithium with improved safety and efficacy as a potential new disease modifying drug for AD.

Use of Lithium in Severe Acute Manic Episodes: Retrospective Prescription Practice From a Tertiary Inpatient Unit.

OBJECTIVE: A retrospective chart review was performed to investigate the common preferences of clinicians for the pharmacological treatment of acute manic episodes, with particular regard to lithium use, and to assess the adherence of clinical practice to established guidelines. METHODS: Cases of manic episodes in patients admitted to Bakirköy Mazhar Osman Mental Health and Neurological Diseases Education and Research Hospital were retrospectively reviewed. Length of stay, medication data, serum levels, and adverse effects were evaluated for patients who received lithium therapy (N=98). RESULTS: On the first day of lithium treatment, 81 patients received 900 to 1200 mg of lithium. In total, 44 patients were discharged with the same dose as that given on the first day of treatment. With the exception of 1 patient, the dose was increased by 300 to 600 mg in the remaining patients within the first 10 days on the basis of serum drug concentrations. The mean serum concentrations of lithium in the first week were 0.67±0.17 mEq/L in patients with no dose increase, and 0.51±0.15 mEq/L in patients who did receive a dose increase. In total, 94 patients received at least 1 antipsychotic medication in addition to lithium. CONCLUSIONS: Clinicians attempted to maintain serum lithium levels above 0.60 mEq/L at the time of acute treatment initiation, consistent with established guidelines. Clinical practice in large inpatient settings may force clinicians to use lithium in combination with antipsychotics for the treatment of acute mania; the delayed action of lithium and the need for rapid stabilization may drive these practices.

Severe chronic lithium intoxication in patient treated for bipolar disorder.

OBJECTIVE: Lithium has been long used in psychiatry as an adjuvant treatment for bipolar disorder. Chronic lithium intoxication is very rare. DESIGN: We present the case of a 72-year-old female, treated with lithium for more than 10 years for bipolar disorder, who was admitted for gait impairment with weakness of limbs, myoclonus, speech impairment and memory disturbances. RESULTS: Diagnosis of lithium intoxication was based on clinical picture and determination of serum lithium levels. EEG showed severe encephalopathy with triphasic wave complexes. Sensory and motor axonal neuropathy was observed by EMG. Discontinuation of the drug leads to clinical improvement, although not to a fully neurological recovery. CONCLUSION: Lithium is still very effective drug, but requires regular monitoring of serum levels to prevent overdose and symptoms of intoxication. Neurophysiological methods, including EEG and EMG, are strongly recommended to determine the level of peripheral and/or central nervous system impairment.

Effect of organo and inorganic lithium salt on human blood plasma glutathione- A comparative study.

Investigation of toxicological effect of various metals is the field of interest for toxicological scientists since four to five decades and especially the toxicological effect of those drugs containing metals and there use is common because there is no other choice except to use these metal containing drugs. Inorganic as well as organic salts of lithium are commonly used in prophylaxis and treatments of many psychiatric disorders. The aim of the present study was to see the difference between the effect of organic and inorganic salt of lithium commonly used in psychiatric disorders on the GSH of human blood plasma. It is the scientific fact that ionic dissociation of organic and inorganic salts of any metal is always quite different hence to prove this fact, the effect of lithium citrate (organic salt of lithium) and lithium carbonate (inorganic salt of lithium) was investigated on human blood plasma GSH to find the difference between the effect of two. Ellman's method was used for the quantification of glutathione contents in plasma. It was found that lithium citrate decrease plasma GSH contents less than lithium carbonate indicating that organic salts of lithium are safe than inorganic salts of lithium when are used in psychiatric disorders. Further to analyze the effect of organic and inorganic salt of lithium on blood plasma GSH with the increase in incubation time was also evaluated and was found that both concentration and time dependent effect of organic salt of lithium shows that this salt has decreased plasma GSH contents of human blood less than inorganic salt of lithium either by promoting oxidation of GSH into GSSG or by lithium glutathione complex formation. These results suggest the physicians that the use of organic lithium salts is much safer than inorganic salts of lithium in terms of depletion of blood plasma GSH contents.

Population Pharmacokinetics of Lithium Carbonate in Young Male Healthy Chinese Volunteers.

Aim: To investigate the population pharmacokinetics (PK) model of lithium carbonate in young male healthy Chinese subjects. Methods: This study was conducted using a 2-period crossover design. 20 healthy male subjects received lithium carbonate tablets from 2 different Chinese pharmaceutical manufacturers. Plasma samples were obtained by blood sampling over 72 h in each period. Population PK analysis was performed using nonlinear mixed-effects model (NONMEM) software. The final models were validated using bootstrap and visual predictive check (VPC) approaches. Results: The final PK model was a two-compartment model. The population PK parameters, clearance (CL/F), apparent distribution volume of the central compartment (V2/F), inter-compartmental clearance (Q/F) and apparent distribution volume of the peripheral compartment (V3/F), were 9.39 L/h, 10.4 L, 22.1 L/h, and 216 L, respectively. Conclusion: Population PK models for lithium carbonate have been developed and considerable inter-subject variability was found in healthy young male Chinese subjects. It takes a long time to achieve the steady state in conventional therapy. This may provide guidelines for future use of lithium carbonate in China.

Artificial Lithium Toxicity: A Case Report and Review of the Literature.

Lithium toxicity results in a range of gastrointestinal and neurologic signs and symptoms and can ultimately be fatal. Serum lithium levels may be unreliable when evaluating patients for toxicity, since levels may not be elevated in patients on chronic lithium therapy. Serum lithium levels may also be artificially elevated if blood is collected in a tube containing lithium heparin. We present a case of a woman on chronic lithium therapy whose lithium level was artificially elevated due to blood collection in an incorrect tube.

Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning.

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 Li2CO3 in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg Li2CO3 in rats receiving 800 mg/l Li2CO3 in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg Li2CO3 during 5 days in rats with 15 mg/kg K2Cr2O7-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 with 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 78 h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379 ± 41 vs 295 ± 26, P < .05) and brain-to-plasma ratio (45 ± 10 vs 8 ± 2, P < .0001) at 54 h]. Moreover, brain lithium distribution was increased in chronically compared with acute-on-chronically poisoned rats (brain-to-plasma ratio: 9 ± 1 vs 3 ± 0, P < .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.

Removal of toxic substances by a selective membrane plasma separator.

We devised a method of plasma exchange with dialysis (PED), in which selective plasma exchange (sPE) is performed using a selective membrane plasma separator (EC-2A) with an albumin-sieving coefficient of 0.3 while the dialysate flows outside the hollow fibers, and reported the usefulness of the system for treating acute liver failure. Thereafter, EC-4A with an albumin-sieving coefficient of 0.6 was developed, which was expected to be even more effective for removing protein-bound substances. In order to examine whether or not EC-4A might be applicable to blood purification therapy against drug poisoning, we compared the efficacies of sPE, PED, and direct hemoperfusion (DHP) using an activated carbon column for the removal of phenobarbital and lithium. Subjects undergoing the extracorporeal circulation study were assigned to the sPE group, PED group, or DHP group, and the changes in the blood concentrations of phenobarbital and lithium were measured over 180 min. A significant decrease of the phenobarbital concentration over time was seen in the PED group, as compared to that in the sPE group (P < 0.0001), while no significant difference in the concentration was observed between the PED and DHP groups. The PED group showed a significant decrease of the lithium concentration over time, as compared to the DHP group (P < 0.0001), while no significant difference in the concentration was observed between the PED and sPE groups. Thus, PED was as effective as DHP for removing phenobarbital and was as effective as sPE for removing lithium. These results suggest that PED therapy using EC-4A may be a feasible modality for the treatment of drug poisoning.

[Metabolic and lithium monitoring in Japanese psychiatric outpatient clinics].

OBJECTIVE: Various guidelines recommend that the risks of diabetes mellitus, dyslipidemia, and lithium intoxication should be appropriately managed by regular monitoring of blood sugar and serum lipid levels in patients treated with atypical antipsychotics, and regular monitoring of serum lithium concentrations in patients treated with lithium carbonate. However, in Japan, these recommendations are not always observed. The present study used a database, constructed from research on medical policies performed in 2006, to investigate the frequencies of blood sugar, serum lipid, and serum lithium monitoring in psychiatric outpatients in Japan. METHODS: This database contained the health insurance claims of 3,674 psychiatric outpatients extracted from the 47 prefectures throughout Japan. The present study examined two subordinate surveys: 1) the frequency of monitoring blood sugar and serum lipid levels in those on atypical antipsychotics during a period of one month (February) in 2006; 2) the frequency of monitoring the serum lithium concentration in those on lithium carbonate, also obtained during February 2006. RESULTS: In Survey 1, the subjects were 228 male and 271 female recipients, with an average age of 45.1 years; 86.8% of these subjects suffered from psychosis. In Survey 2, the subjects were 70 male and 64 female recipients, with an average age of 49.9 years; 57.5% of these subjects suffered from mood disorder and 36.6% suffered from psychosis. In Survey 1, the blood sugar level, HbA1c, and urinary sugar were monitored in 28 (5.6%), 5 (1.0%), and 8 (1.6%) subjects, respectively. At least one of these three tests was performed in 32 subjects (6.4%). The serum lipid level was monitored in 40 subjects (8.0%). In Survey 2, no serum lithium concentrations were measured. The frequency of monitoring the serum lithium concentration per month was estimated to be below 2.2%. CONCLUSIONS: The Maudsley Prescribing Guidelines recommend that both blood sugar and serum lipid levels should be monitored at least once a year (equivalent to a measurement frequency of 8.3% per month). Survey 1 revealed that, although the actual frequency of monitoring the serum lipid level agreed with the recommendation, that of monitoring the blood sugar level was lower than recommended. However, when compared with the results of a study in the U.S.(equivalent to a measurement frequency of 2-17% per month), the frequency of monitoring the blood sugar level was not that low in Japan. The frequency of monitoring the serum lithium concentration per month was estimated to be below 2.2%. The guidelines and package inserts recommend that the serum lithium concentration should be monitored once every 2-6 months. Therefore, the frequency of monitoring the serum lithium concentration in psychiatric outpatients treated in Japan was considered to be too low from the standpoint of medical safety.

Lithium dosing equations: are they accurate?

BACKGROUND: Several equations are used to predict lithium doses necessary to attain therapeutic serum concentrations. A number of studies have evaluated these equations; however, few equations were compared simultaneously. OBJECTIVE: To assess the accuracy and precision of published dosing equations in predicting daily lithium doses and to evaluate if pertinent laboratory tests were performed prior to initiation. METHODS: A retrospective analysis was performed of patients who received lithium at the Medical University of South Carolina Institute of Psychiatry between July 2010 and July 2012. Using dosing equations, expected lithium doses were calculated based on corresponding serum concentrations identified in patient charts. Expected doses were then compared with actual lithium doses. The primary end point was to assess the accuracy and precision of dosing equations using mean differences in daily lithium doses and standard deviations. Secondary end points included presence of pertinent laboratory tests and use of concomitant interacting drugs . RESULTS: Of 155 patients identified, 59 were eligible for analysis. Equations developed by Abou-Auda et al and Pepin et al did not predict doses that were significantly different from actual doses. Conversely, equations by Jermain et al, Terao et al, and Zetinet al did predict statistically different doses. CONCLUSIONS: Abou-Auda et al developed a predictive lithium dosing equation that was more accurate than equations developed by Jermain et al, Terao et al, and Zetin et al and more precise than the Pepin et al equation. Further study evaluating the influence of equations on clinical outcomes is warranted.

Prescribing patterns of lithium or lithium+valproate in manic or mixed episodes: a naturalistic study.

The present study aimed to identify the prescribing patterns of lithium or of lithium+valproate in 75 bipolar I outpatients in a manic or a mixed phase within a naturalistic setting. The differences between the two treatments and the correlation between serum lithium levels and response were also examined. The results showed that patients with lithium levels of 0.60 mEq/l or more had higher remission rates and greater symptom reduction than the other patients. Patients on lithium and valproate showed greater improvement in mixed, anxiety, and psychotic symptoms than those on lithium only, as assessed by the Clinical Global Impression-Bipolar version scale scores. Finally, our findings suggest that a range of lithium levels between 0.40 and 0.60 mEq/l, albeit below the therapeutic range, seems sufficient to maintain a good effect when lithium is coadministered with valproate.

Bipolar disorder and medication: adherence, patients' knowledge and serum monitoring of lithium carbonate.

OBJECTIVES: this study featured patients with affective bipolar disorder who were making use of lithium and received care at an outpatient care center located in a country town in the state of Sao Paulo in 2009; it assessed the adherence and knowledge of these patients in relation to the medication prescribed to them and verified the proportion of blood tests performed per year in the service, for each individual, to measure lithium levels in the blood. METHOD: descriptive study with quantitative approach, involving 36 participants. Structured interviews and review of medical records were used for data collection and descriptive statistics for data analysis. RESULTS: difficulties in reporting the dosage of the medication prescribed and a high rate of non-adherence were identified among the participants. None of the participants in the study was submitted to two tests a year to measure lithium levels in the blood, which is the minimum proportion of tests recommended by the literature for maintenance treatment using lithium carbonate. CONCLUSION: this study highlights the critical factors for the promotion of patients' safety in monitoring lithium drug therapy.

Bipolar disorder and medication: adherence, patients' knowledge and serum monitoring of lithium carbonate / Transtorno bipolar e medicamentos: adesão, conhecimento dos pacientes e monitorização sérica do carbonato de lítio / Trastorno bipolar y medicamentos: adhesión, conocimiento de los pacientes y monitorización sérica del carbonato de litio

OBJECTIVES: this study featured patients with affective bipolar disorder who were making use of lithium and received care at an outpatient care center located in a country town in the state of Sao Paulo in 2009; it assessed the adherence and knowledge of these patients in relation to the medication prescribed to them and verified the proportion of blood tests performed per year in the service, for each individual, to measure lithium levels in the blood. METHOD: descriptive study with quantitative approach, involving 36 participants. Structured interviews and review of medical records were used for data collection and descriptive statistics for data analysis. RESULTS: difficulties in reporting the dosage of the medication prescribed and a high rate of non-adherence were identified among the participants. None of the participants in the study was submitted to two tests a year to measure lithium levels in the blood, which is the minimum proportion of tests recommended by the literature for maintenance treatment using lithium carbonate. CONCLUSION: this study highlights the critical factors for the promotion of patients' safety in monitoring lithium drug therapy. .

OBJETIVOS: este estudo teve como objetivo caracterizar pacientes com transtorno afetivo bipolar, em uso de lítio, atendidos no ano 2009 em um serviço ambulatorial do interior de São Paulo, Brasil; avaliar a adesão e conhecimento dos mesmos sobre medicamentos prescritos e verificar a proporção de litemias/ano realizadas, no serviço, para cada indivíduo. MÉTODO: trata-se de estudo descritivo, com abordagem quantitativa, do qual participaram 36 pessoas. Foram utilizadas entrevistas estruturadas e revisão de prontuários para coleta de dados e estatística descritiva para análise dos mesmos. RESULTADOS: entre os participantes, foram identificadas dificuldades em relatar a dose dos fármacos prescritos e alta taxa de não adesão. Em nenhum participante do estudo foi atingida a proporção de duas litemias/ano, que representa a quantidade mínima de litemias preconizada pela literatura para o tratamento de manutenção com carbonato de lítio. CONSIDERAÇÕES FINAIS: este estudo aponta fatores críticos na promoção da segurança do paciente no seguimento da terapêutica medicamentosa com lítio. .

OBJETIVOS: este estudio caracterizó pacientes con trastorno afectivo bipolar, tratadas con litio, atendidos en el año de 2009 en un servicio de ambulatorio del interior del estado de Sao Paulo, en Brasil; evaluó la adhesión y conocimiento de los mismos sobre medicamentos prescritos y verificó la proporción de litemias/año realizadas, en el servicio, para cada individuo. MÉTODO: se trata de estudio descriptivo, con abordaje cuantitativo, del cual participaron 36 personas. Fueron utilizadas entrevistas estructuradas y revisión de fichas para recolección de datos y estadística descriptiva para análisis de los mismos. RESULTADOS: entre los participantes, fueron identificadas dificultades en relatar la dosis de los fármacos prescritos y una alta tasa de no adhesión. En ningún participante del estudio fue alcanzada la proporción de dos litemias/año, que representa la cantidad mínima de litemias preconizada por la literatura para el tratamiento de mantenimiento con carbonato de litio. CONCLUSIÓN: este estudio apunta factores críticos para la promoción de la seguridad del paciente en el seguimiento de la terapéutica medicamentosa con litio. .