RESUMEN
Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine). Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44-0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures.
Asunto(s)
Antimaníacos , Antipsicóticos , Trastorno Bipolar , Fracturas Óseas , Humanos , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Antipsicóticos/efectos adversos , Fracturas Óseas/epidemiología , Fracturas Óseas/inducido químicamente , Antimaníacos/efectos adversos , Antimaníacos/uso terapéutico , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Estudios de Cohortes , Compuestos de Litio/efectos adversos , Compuestos de Litio/uso terapéutico , Anciano , Reino Unido/epidemiología , Litio/uso terapéutico , Litio/efectos adversosRESUMEN
Previous research examining bipolar-disorder (BD) and pregnancy/neonatal outcomes yielded mixed results, were mostly derived from Western countries and rarely delineated effect between disorder and mood-stabilizers. This population-based study identified women age 15-50 years who delivered first/singleton child in 2003-2018 in Hong Kong, utilizing territory-wide medical-record database of public healthcare services. Propensity-score weighted logistic-regression analyses adjusted for confounders were employed to examine risk of adverse pregnancy, delivery and neonatal outcomes associated with BD and mood-stabilizers (lithium, anticonvulsants and antipsychotics). Exploratory unadjusted-analyses were conducted to assess risk for congenital-malformations. Of 465,069 women, 302 had BD-diagnosis, including 168 redeemed ≥ 1 prescription of mood-stabilizers during pregnancy (treated-BD) and 134 gestationally-unexposed to mood-stabilizers (untreated-BD). BD was significantly-associated with increased risk of gestational-diabetes (adjusted-odds-ratio: 1.75 [95 % CI: 1.15-2.70]) and maternal somatic hospitalization ≤ 90 days post-discharge from index-delivery (2.12 [1.19-3.90]). In treatment status-stratified analyses, treated-BD women exhibited significantly-increased rate of gestational-diabetes (2.09 [1.21-3.70]) relative to controls (non-BD and gestationally-unexposed to mood-stabilizers). No significant association of BD or mood-stabilizers with other adverse outcomes was observed. Overall, our findings indicate that BD and mood-stabilizers are not associated with most adverse pregnancy, delivery and neonatal outcomes. Further research clarifying comparative safety of individual mood-stabilizing agents on pregnancy/neonatal outcomes is required.
Asunto(s)
Anticonvulsivantes , Antipsicóticos , Trastorno Bipolar , Complicaciones del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/epidemiología , Adulto , Adulto Joven , Adolescente , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/tratamiento farmacológico , Hong Kong/epidemiología , Recién Nacido , Anticonvulsivantes/efectos adversos , Resultado del Embarazo/epidemiología , Antipsicóticos/efectos adversos , Antimaníacos/efectos adversos , Persona de Mediana Edad , Estudios de Cohortes , Diabetes Gestacional/epidemiología , Diabetes Gestacional/tratamiento farmacológico , Compuestos de Litio/efectos adversosRESUMEN
BACKGROUND: Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association. METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models. RESULTS: Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77-1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer's disease (OR = 0.69, 95% CI: 0.31-1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71-1.15). CONCLUSION: The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.
Asunto(s)
Trastorno Bipolar , Compuestos de Litio , Humanos , Compuestos de Litio/efectos adversos , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/inducido químicamente , Trastornos Neurocognitivos/inducido químicamente , Trastornos Neurocognitivos/epidemiología , Antimaníacos/efectos adversos , Litio/efectos adversosRESUMEN
BACKGROUND: The extent of parathyroidectomy (PTX) recommendation in patients with lithium-associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long-term outcomes. METHODS: A population-based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non-LAH). RESULTS: Lithium exposure was significantly more common among PHPT (n = 202, 2.3%) than in controls (n = 416, 0.5%); OR 5.0 (95% CI 4.2-5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH-group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re-admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5 years duration of lithium exposure prior to surgery. CONCLUSIONS: The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence.
Asunto(s)
Hiperparatiroidismo Primario , Paratiroidectomía , Humanos , Femenino , Masculino , Persona de Mediana Edad , Paratiroidectomía/efectos adversos , Suecia/epidemiología , Anciano , Hiperparatiroidismo Primario/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/inducido químicamente , Litio/efectos adversos , Compuestos de Litio/efectos adversos , Sistema de Registros , Resultado del Tratamiento , Adulto , Estudios RetrospectivosRESUMEN
Bipolar disorder is associated with increased rates of many physical disorders, but the effects of medication are unclear. We systematically investigated the associations between sustained use of first line maintenance agents, lithium versus lamotrigine and valproate, and the risk of physical disorders using a nation-wide population-based target trial emulation covering the entire 5.9 million inhabitants in Denmark. We identified two cohorts. Cohort 1: patients with a diagnosis of bipolar disorder prior to first purchase (N = 12.607). Cohort 2: all 156.678 adult patients who had their first ever purchase (since 1995) of either lithium, lamotrigine or valproate between 1997 and 2021 regardless of diagnosis. Main analyses investigated the effect of sustained exposure defined as exposure for all consecutive 6-months periods during a 10-year follow-up. Outcomes included a diagnosis of incident stroke, arteriosclerosis, angina pectoris, myocardial infarction, diabetes mellitus, myxedema, osteoporosis, dementia, Parkinson's disease, chronic kidney disease and cancer (including subtypes). In both Cohorts 1 and 2, there were no systematic statistically significant differences in associations between sustained use of lithium versus lamotrigine and valproate, respectively, and any physical disorder, including subtypes of disorders, except myxedema, for which exposure to lithium increased the absolute risk of myxedema with 7-10 % compared with lamotrigine or valproate. In conclusion, these analyses emulating a target trial of "real world" observational register-based data show that lithium does not increase the risk of developing any kind of physical disorders, except myxedema, which may be a result of detection bias.
Asunto(s)
Anticonvulsivantes , Trastorno Bipolar , Lamotrigina , Humanos , Femenino , Masculino , Dinamarca/epidemiología , Persona de Mediana Edad , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Trastorno Bipolar/epidemiología , Trastorno Bipolar/tratamiento farmacológico , Adulto , Anciano , Lamotrigina/efectos adversos , Lamotrigina/uso terapéutico , Antimaníacos/efectos adversos , Antimaníacos/uso terapéutico , Estudios de Cohortes , Compuestos de Litio/efectos adversos , Compuestos de Litio/uso terapéutico , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéuticoRESUMEN
PURPOSE: The aim of this study was to compare the efficacy and safety profile of lurasidone combined with either lithium or valproate, in the short-term treatment of patients with bipolar depression. METHODS: Data were pooled from two 6-week, double-blind, placebo-controlled trials of patients with bipolar depression on stable doses of lithium or valproate randomized to lurasidone (20-120 mg/d) or placebo. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions Bipolar Scale, and the Quick Inventory of Depressive Symptomatology via self-assessment and were analyzed using a mixed model for repeated measures approach. RESULTS: Notably larger week 6 effect sizes were observed when lurasidone was added to lithium, compared with when lurasidone was added to valproate, on 2 of the 3 depression outcome measures, Montgomery-Åsberg Depression Rating Scale total score (d = 0.45 vs 0.22) and Quick Inventory of Depressive Symptomatology via self-assessment (d = 0.63 vs 0.29); the efficacy advantage was smaller on the Clinical Global Impressions Bipolar Scale depression score (d = 0.34 vs 0.29). Similar adverse event profiles were observed for lurasidone treatment in combination with either lithium or valproate. The most frequently reported events (≥5%) in both groups were nausea, parkinsonism, somnolence, akathisia, and insomnia. Minimal changes in weight, lipids, and measures of glycemic control were observed during treatment with lurasidone combined with either lithium or valproate. CONCLUSIONS: Lurasidone added to either lithium or valproate was found to be an effective treatment for bipolar depression, with a larger antidepressant effect observed when lurasidone was combined with lithium. There were no clinically meaningful differences in the safety or tolerability of lurasidone when used adjunctively with lithium or valproate.
Asunto(s)
Antimaníacos , Trastorno Bipolar , Quimioterapia Combinada , Clorhidrato de Lurasidona , Ácido Valproico , Humanos , Clorhidrato de Lurasidona/administración & dosificación , Clorhidrato de Lurasidona/efectos adversos , Clorhidrato de Lurasidona/farmacología , Clorhidrato de Lurasidona/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Ácido Valproico/administración & dosificación , Ácido Valproico/efectos adversos , Ácido Valproico/farmacología , Ácido Valproico/uso terapéutico , Femenino , Masculino , Adulto , Método Doble Ciego , Antimaníacos/administración & dosificación , Antimaníacos/efectos adversos , Antimaníacos/farmacología , Persona de Mediana Edad , Resultado del Tratamiento , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Antipsicóticos/farmacología , Compuestos de Litio/administración & dosificación , Compuestos de Litio/efectos adversos , Compuestos de Litio/farmacología , Escalas de Valoración PsiquiátricaRESUMEN
More than 25 years after being diagnosed with bipolar disorder and receiving continuous treatment with lithium, a woman develops Takotsubo syndrome.
Asunto(s)
Trastorno Bipolar , Cardiomiopatía de Takotsubo , Femenino , Humanos , Litio/uso terapéutico , Cardiomiopatía de Takotsubo/inducido químicamente , Cardiomiopatía de Takotsubo/diagnóstico , Cardiomiopatía de Takotsubo/complicaciones , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/complicaciones , Antidepresivos/uso terapéutico , Compuestos de Litio/efectos adversosRESUMEN
OBJECTIVES: Severe polyhydramnios during pregnancy may be associated with long-term lithium use and presents considerable challenges. This complication, which has been linked to induced nephrogenic diabetes insipidus (NDI), underscores the necessity for cautious management of pregnant women with bipolar disorder. This case report aims to elucidate the relationship between long-term lithium use, pregnancy, and the development of severe polyhydramnios, emphasizing the importance of diagnosing NDI in order to prevent obstetric and neonatal complications. METHODS: We present the case of a 42-year-old primigravida undergoing long-term lithium treatment for bipolar disorder type I, who developed severe polyhydramnios at 34 weeks of gestation. Clinical data including obstetric monitoring and neonatal outcomes were analyzed. RESULTS: This case emphasizes the need for heightened awareness and proactive measures to mitigate the risk associated with lithium treatment during pregnancy. Close monitoring and timely interventions are essential to ensure optimal outcomes for both mother and fetus. CONCLUSIONS: Our article puts forth the hypothesis that there is a link between lithium use during pregnancy and the occurrence of polyhydramnios and Nephrogenic Diabetes Insipidus (NDI), which may lead to severe obstetric and neonatal complications. This case report contributes to the limited literature on the subject and gives doctors practical advice that may help them make a better risk-benefit analysis. Further research is warranted in order to refine risk assessment protocols and management strategies in this complex clinical scenario.
Asunto(s)
Antimaníacos , Trastorno Bipolar , Polihidramnios , Humanos , Femenino , Embarazo , Polihidramnios/inducido químicamente , Adulto , Trastorno Bipolar/tratamiento farmacológico , Antimaníacos/efectos adversos , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/inducido químicamente , Compuestos de Litio/efectos adversos , Diabetes Insípida Nefrogénica/inducido químicamente , Diabetes Insípida Nefrogénica/diagnósticoRESUMEN
We report a case study of a 60-year-old man with bipolar disorder on stable lithium treatment who developed severe toxicity while admitted to ICU with sepsis and multiorgan failure. Despite unchanged lithium administration, his serum levels escalated due to renal dysfunction, resulting in lithium toxicity. After regaining consciousness, he exhibited a cerebellar syndrome marked by ataxia, tremor, and scanning speech. MRI revealed cerebellar atrophy. Following discontinuation of lithium and hemodialysis, the patient's symptoms remained static. The patient was diagnosed with syndrome of irreversible lithium-effectuated neurotoxicity (SILENT), a chronic cerebellar disorder characterized by persistent ataxia, nystagmus, and gait abnormalities extending beyond two months post-lithium exposure. The disorder has a predilection for cerebellar and basal ganglia dysfunction. MRI findings include cerebellar gliosis and atrophy and leptomeningeal enhancement. This case report highlights that SILENT is both preventable and permanent, urging heightened awareness among clinicians to facilitate early detection and intervention. Patients on lithium with compromised renal function or fever necessitate vigilant lithium level monitoring, dose adjustment, or cessation, to forestall enduring morbidity. This case emphasizes the significance of recognizing and managing SILENT, particularly in critical care settings, to mitigate long-term cerebellar impairment and optimize patient outcomes.
Asunto(s)
Enfermedades Cerebelosas , Síndromes de Neurotoxicidad , Humanos , Masculino , Persona de Mediana Edad , Síndromes de Neurotoxicidad/etiología , Enfermedades Cerebelosas/inducido químicamente , Enfermedades Cerebelosas/diagnóstico por imagen , Trastorno Bipolar/tratamiento farmacológico , Imagen por Resonancia Magnética , Compuestos de Litio/efectos adversos , Cerebelo/efectos de los fármacos , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Antimaníacos/efectos adversosRESUMEN
BACKGROUND: There has been no previous study in Thailand regarding the incidence of lithium-induced abnormal renal function. Hence, this study aimed to assess the effect of lithium maintenance therapy on chronic kidney disease, and associated factors among outpatients diagnosed with a psychiatric illness within Southern Thailand. METHODS: This was a retrospective study, using an information review from the electronic medical records of Songklanagarind Hospital computer system in the last ten years; from 1 January 2013 until 31 September 2022. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 and persisted for three months or more. There were 461 outpatients diagnosed with a psychiatric illness who received lithium maintenance therapy. From this, 154 outpatients were excluded: 153 received lithium therapy for less than three months and 1 presented with a baseline chronic kidney disease. All data were analyzed using Rstudio 4.3.1. The incidence of lithium-induced chronic kidney disease was analyzed by survival analysis. RESULTS: Of the 307 outpatients diagnosed with a psychiatric illness and received lithium maintenance therapy, the most common diagnosis was bipolar disorder (59.3%). Most were female (52.8%), with the median (IQR) age of 39.0 (27.5-54.0) years. The median (IQR) age onset of lithium therapy and duration of lithium maintenance therapy were 28.0 (21.0-41.5) years, and 2.97 (0.9-9.2) years, respectively. This study identified six outpatients (1.9%) that developed chronic kidney disease stage 3 or more and one of them (0.3%) presented with chronic kidney disease stage 5 or end-stage. The incidence of lithium-induced chronic kidney disease was 0.0023 cases per exposed patient-year. When comparing outpatients who had received lithium maintenance therapy and developed chronic kidney disease with those who did not develop chronic kidney disease, this study identified that most of the group with chronic kidney disease had a lithium maintenance therapy for more than ten years, had an older age onset of lithium therapy, reported history of psychiatric hospitalization and lithium intoxication, and presented with physical illness. The associated factors between the effect of lithium maintenance therapy and chronic kidney disease could not be identified due to a limited number of outpatients having developed chronic kidney disease. CONCLUSIONS: Lithium-induced chronic kidney disease was identified as a minor incidence, and it was likely safe for maintenance therapy with careful and regular monitoring. However, older patients or those receiving lithium for a longer time and present with comorbid physical illnesses should be prescribed with caution. IRB / IEC CERTIFICATION: 65-389-3-4.
Asunto(s)
Trastorno Bipolar , Compuestos de Litio , Insuficiencia Renal Crónica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/epidemiología , Hospitales , Incidencia , Compuestos de Litio/efectos adversos , Pacientes Ambulatorios , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Tailandia/epidemiología , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/epidemiologíaRESUMEN
La diabetes insípida (DI) es un síndrome caracterizado por poliuria y polidipsia asociado a la producción crónica de grandes volúmenes de orina diluida, secundario a una disminución de la secreción o acción de la hormona antidiurética (ADH) [1]. El litio es el principal fármaco implicado en la inducción de esta patología cuando se presenta de forma secundaria. [2]. Se presentan 2 reportes de casos de niños de 10 y 12 años con uso de litio por diagnóstico de trastorno del ánimo. Palabras Clave: Diabetes Melitus, trastornos del ánimo, nefrogénica, litio, hormona antidiurética
Diabetes insipidus (DI) is a syndrome characterized by polyuria and polydipsia associated with the production of large volumes of diluted urine, secondary to a decrease in the secretion or action of antidiuretic hormone (ADH) [1]. Lithium is the main drug involved in the induction of this pathology when it appears with a preventable cause [2]. Two case reports of children 10 and 12 years old with mood disorder and lithium use are presented with the intention of being alert to clinical manifestations and observation by caregivers.Key words: Diabetes insipidus, mood disorders, nephogenic, lithium, antidiuretic hormone.
Asunto(s)
Humanos , Masculino , Niño , Trastorno Bipolar/tratamiento farmacológico , Compuestos de Litio/uso terapéutico , Diabetes Insípida Nefrogénica/etiología , Antidepresivos/uso terapéutico , Compuestos de Litio/efectos adversosRESUMEN
El término tiroiditis comprende un grupo de enfermedades de la glándula tiroides caracterizado por la presencia de inflamación, abarcando entidades autoinmunes y no-autoinmunes. Pueden manifestarse como enfermedades agudas con dolor tiroideo severo (tiroiditis subaguda y tiroiditis infecciosas), y condiciones en las cuales la inflamación no es clínicamente evidente, cursando sin dolor y presentando disfunción tiroidea y/o bocio (tiroiditis inducida por fármacos y tiroiditis de Riedel). El objetivo de esta revisión es aportar un enfoque actualizado sobre las tiroiditis no-autoinmunes cubriendo sus aspectos clínicos, diagnósticos y terapéuticos.
The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.
Asunto(s)
Humanos , Tiroiditis/diagnóstico , Tiroiditis/etiología , Tiroiditis/terapia , Tiroiditis Subaguda/diagnóstico , Tiroiditis Supurativa/diagnóstico , Tiroiditis Supurativa/etiología , Tiroiditis Supurativa/terapia , Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedad Crónica , Interferón-alfa/efectos adversos , Compuestos de Litio/efectos adversos , Diagnóstico Diferencial , Glucocorticoides/uso terapéutico , Bocio/complicaciones , Amiodarona/efectos adversosRESUMEN
Las alteraciones del funcionamiento de la glándula tiroidea influyen en la estabilidad afectiva repercutiendo negativamente en el curso clínico de la enfermedad bipolar. El principal estabilizador utilizado en este trastorno, las sales de litio, ejerce numerosos efectos sobre la fisiología del tiroides. La inhibición del recambio de la hormona tiroidea, que puede producirse con niveles terapéuticos de sales de litio, es el que tiene mayor relevancia clínica. Por otro lado, la disfunción tiroidea también parece ser más frecuente en pacientes bipolares no tratados con litio. Al margen de las numerosas complicaciones médicas y afectivas, también el sistema perceptivo o el cognitivo pueden verse afectados. De hecho, la presencia de una enfermedad tiroidea aumenta las tasas de trastorno obsesivo compulsivo, fobias, trastorno de pánico, trastorno depresivo mayor, ciclotimia o trastorno bipolar (TB). En casos de hipotiroidismo grave, la clínica puede ser semejante a una depresión melancólica o a una demencia. Por ello, en la práctica clínica diaria, es importante conocer bien los efectos de las sales de litio sobre la función tiroidea. En esta revisión abordaremos las principales disfunciones tiroideas presentes en los pacientes bipolares, generadas o no por el tratamiento con sales de litio, y aportaremos una serie de recomendaciones para su manejo clínico (AU)
Thyroid disfunction affects negatively emotional stability and worsens the clinical course of bipolar affective disorder. The main stabilizer used in this illness, lithium carbonate has numerous effects on the physiology of the thyroid, with the most significant being the inhibition of thyroid hormone release that may occur at therapeutic levels. These dysfunctions have also been reported most frequently in bipolar patients not undergoing treatment with lithium, and was not completely explained by the effects of this drug. Apart from the numerous medical complications and mood disturbances, the cognitive or perceptual system may also be affected. In fact, he presence of thyroid disease increases the rates of obsessive compulsive disorder, phobias, panic disorder, major depressive disorder, cyclothymia, or bipolar disorder. In severe cases of hypothyroidism, the clinical symptoms and signs can be similar to a melancholic depression or dementia. It is therefore important to know well all these possible complications in daily clinical practice. This review will cover the main thyroid dysfunctions present in bipolar patients, whether to not produced by treatment with lithium carbonate, and will provide a series of recommendations for clinical management (AU)
Asunto(s)
Humanos , Trastorno Bipolar/complicaciones , Glándula Tiroides , Compuestos de Litio/efectos adversos , Carbamazepina/efectos adversos , Enfermedades de la Tiroides/inducido químicamente , Factores de RiesgoRESUMEN
Despite recent advances in pharmacological treatment of psychiatric disorders, lithium salts remain frequently used, as they are effective and inexpensive alternatives, especially in the treatment of bipolar disorders. Their use is commonly associated with various endocrine disorders, mainly in thyroid and parathyroid function, and in mineral metabolism. This article aims at reviewing these potential endocrinopathies related to the use of lithium to make health care professionals aware and familiar with these possible complications when they follow up patients using this drug, and to make them able to monitor, identify and institute early and appropriate treatment.
Apesar dos recentes avanços farmacológicos no tratamento dos transtornos psiquiátricos, os sais de lítio permanecem como uma alternativa eficaz e de menor custo, sendo usados com frequência principalmente no tratamento dos transtornos bipolares. O seu uso é comumente relacionado com diversas alterações endocrinológicas, principalmente nas funções tiroidiana, paratiroidiana e do metabolismo iônico. Este artigo tem por objetivo fazer uma revisão dessas potenciais endocrinopatias relacionadas ao uso do lítio, para que, no seguimento de pacientes em uso dessa medicação, os profissionais de saúde estejam atentos e familiarizados com essas possíveis complicações, conseguindo identificar e instituir tratamento precocemente.
Asunto(s)
Humanos , Enfermedades del Sistema Endocrino/inducido químicamente , Compuestos de Litio/efectos adversos , Glándulas Paratiroides/efectos de los fármacos , Glándula Tiroides/efectos de los fármacos , Glucemia/metabolismo , Diabetes Insípida Nefrogénica/inducido químicamente , Trastornos Mentales/tratamiento farmacológicoRESUMEN
Desde hace más de cuarenta años que el litio es usado para el tratamiento de la enfermedad bipolar; recientes estudios sugieren también su utilidad en el trastorno cognitivo mínimo tipo amnésico. El litio es filtrado en el glomérulo y un 65-75% del mismo es reabsorbido en el túbulo contorneado proximal y en el asa ascendente de Henle por el transportador Na+, K+, 2Cl- y vía paracelular. Una pequeña fracción del litio entra en las células principales del túbulo colector por medio del canal epitelial de sodio sensible al amiloride (ENaC) localizado en la membrana apical de la célula. Luego de 10- 20 años de tratamiento con litio los enfermos pueden desarrollar poliuria, acidosis tubular e insuficiencia renal crónica que puede terminar en una forma de diabetes que no responde a la arginina vasopresina llamada diabetes insípida nefrogénica. Se cree que estas fallas renales son consecuencias de una reducción en el número de moléculas de acuaporina 2 en la membrana apical. Las causas para esto son complejas. El litio es un poderoso inhibidor de la isoforma beta de la enzima glicógeno sintetasa quinasa y esto está asociado a una menor actividad de la adenilato ciclasa que lleva a una disminución en la concentración intracelular de cAMP. Esto finalmente interferiría con la síntesis de nuevas moléculas de acuaporina 2 y con el tráfico de ellas desde la zona subapical de la célula hacia la membrana celular, causando la disminución en la reabsorción de agua en la parte distal del nefrón.
For more than 40 years lithium has been used to treat bipolar disorder and recent trials suggest a potential efficacy also in the treatment of the amnestic mild cognitive impairment. Lithium is filtered by the glomerulus and 65% - 75% of the filtered amount is reabsorbed along the proximal tubule and in the thick ascending limb of Henle's loop by the Na+, K+, 2Cl- transporter and via paracellular. A small fraction of lithium is reabsorbed in the collecting duct's principal cells through the epithelial Na channel (ENaC) located on the apical side of the cells. Polyuria, renal tubular acidosis and chronic renal failure are the most frequent adverse effects of lithium after 10-20 years of treatment and these alterations can reach to a vasopressin nonresponding form of diabetes insipidus entity called nephrogenic diabetes insipidus. It is believed that the molecular mechanisms of these renal changes are related to a reduction in the number of aquaporin-2 inserted in the apical membrane of the cells. The causes of this are complex. Lithium is a powerful inhibitor of the enzyme glycogen synthase kinase 3β and this is associated with a lower activity of adenylate cyclase with a reduction in the cAMP levels inside of the cells. The latter may interfere with the synthesis of aquaporin-2 and also with the traffic of these molecules from the subapical site to membrane promoting the impairment of water reabsorption in the distal part of the kidney.
Asunto(s)
Animales , Antimaníacos/uso terapéutico , /fisiología , Canales Epiteliales de Sodio/fisiología , Compuestos de Litio/uso terapéutico , Antimaníacos/efectos adversos , Antimaníacos/metabolismo , Trastorno Bipolar/tratamiento farmacológico , Diabetes Insípida Nefrogénica/inducido químicamente , Enfermedades Renales/fisiopatología , Riñón/efectos de los fármacos , Riñón/metabolismo , Compuestos de Litio/efectos adversos , Compuestos de Litio/metabolismo , Litio/efectos adversos , Litio/metabolismo , Litio/farmacologíaRESUMEN
Si bien las complicaciones neurológicas asociadas con la intoxicación aguda por litio son conocidas desde hace más de setenta años, sólo recientemente se han estudiado en profundidad las secuelas neurológicas permanentes asociadas con el uso de litio. El acrónimo SILENT (Syndrome of Irreversible Lithium-Effectuated Neurotoxicity) ha sido acuñado para definer estas secuelas. Las características especiales farmacocinéticas del litio, junto con su nula unión a proteínas plasmáticas y su capacidad de acumulación en diferentes tejidos, podrían explicar en parte la falta de correlación entre las litemias y la gravedad de las secuelas neurológicas. A partir del estudio y descripción de un caso ingresado en una unidad de hospitalización psiquiátrica se analizan los mecanismos fisiopatológicos de las secuelas permanentes tras una intoxicación por litio. Se describe el caso de un varón de mediana edad que, tras una intoxicación por litio con niveles plasmáticos superiores a 4 mEq/L, tratado únicamente con diuresis forzada, presenta un síndrome demencial grave con disartria, disfagia global, ataxia grave y alteraciones respiratorias centrales. Tras estudiar el caso, se observó que habían concurrido varias circunstancias de manera simultánea que incrementarían el riesgo de toxicidad aguda: una caída brusca de los niveles de litio desde valores tóxicos: factores de riesgo individual como son insuficiencia renal, tratamiento de la HTA con hidroclorotiazidas y edad superior a50 años, y finalmente un tratamiento inadecuado de la intoxicación, ya que la hemodiálisis habría sido la terapia de elección en el caso de una intoxicación grave en un paciente crónicamente tratado con este fármaco
Although the acute complications of lithium toxicity involving the central nervous system have been known for the more than 70 years, it is Orly recently that the longlasting sequelae of lithium intoxication have come to be discussed at length. The acronysm SILENT(Syndrome of Irreversible Lithium- Effectuated Neurotoxicity) has been coined recently to denote these sequelae. The peculiar pharmacokinetic characteristics of lithium, as its tendency to accumulate in many tissues with an absolute absence of linkage to plasmatic proteins, could explain the poor correlation between plasmatic lithium levels and the severity of neurological sequelae after an intoxication. Following the study and depiction of a patient admitted at a psychiatric unit at Hospital de Conxo in Santiago de Compostela (Spain), our aim is to analyze the physiopathological mechanisms of longlasting sequelae after lithium poisoning. We present the case of a middle-aged man who developed a severe demential syndrome with ataxia, dysarthria global dysphasia and central respiratory alterations following a lithium intoxication. The lithium serum levels reached 4mEq/L, but he was only treated with forced diuresis. We report several circumstances that can increase the risk of acute toxicity, including a rapid decrease in serum levels; individuals risk factors as a previous renal impairment concomitant treatment with hidroclorotiazides and an age over fifty; and finally; an unappropriate treatment of the condition, haemodialysis being the desirable one in a case of acute lithium poisoning in a patient chronically treated with the drug