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1.
Cells ; 10(2)2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525562

RESUMO

Lithium salts have been in the therapeutic toolbox for better or worse since the 19th century, with purported benefit in gout, hangover, insomnia, and early suggestions that lithium improved psychiatric disorders. However, the remarkable effects of lithium reported by John Cade and subsequently by Mogens Schou revolutionized the treatment of bipolar disorder. The known molecular targets of lithium are surprisingly few and include the signaling kinase glycogen synthase kinase-3 (GSK-3), a group of structurally related phosphomonoesterases that includes inositol monophosphatases, and phosphoglucomutase. Here we present a brief history of the therapeutic uses of lithium and then focus on GSK-3 as a therapeutic target in diverse diseases, including bipolar disorder, cancer, and coronavirus infections.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Animais , Antimaníacos/farmacologia , Transtorno Bipolar/metabolismo , Coronavirus/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Compostos de Lítio/farmacologia , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Síndrome Respiratória Aguda Grave/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Medicine (Baltimore) ; 99(42): e22823, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080761

RESUMO

INTRODUCTION/RATIONALE: Multiple sclerosis (MS) is associated with a higher prevalence of mood and psychiatric disorders, such as bipolar disorder (BD). While mania is most often associated with BD, MS can also induce manic symptoms. However, it is crucial to distinguish which condition is causing mania since medical management is different based on its etiology. Herein, we report a case of a manic episode in a middle-aged female with a prolonged history of BD who received a recent diagnosis of MS 1 year ago. PATIENT CONCERNS: A 56-year-old female presented with an episode of mania and psychosis while receiving a phenobarbital taper for chronic lorazepam use. She had a prolonged history of bipolar type 1 disorder and depression. She showed optic neuritis and was diagnosed with MS a year prior. DIAGNOSES: The patient was diagnosed with BD-induced mania based on the absence of increased demyelination compared to previous MRI and lack of new focal or lateralizing neurologic findings of MS. INTERVENTIONS: Lithium was given for mood stabilization and decreased dosage of prior antidepressant medication. Risperidone was given for ongoing delusions. OUTCOMES: After 8 days of hospitalization, patient's mania improved but demonstrated atypical features and ongoing delusions. She was discharged at her request to continue treatment in an outpatient setting. CONCLUSION/LESSON: In BD patients with an episode of mania, MS should be included in the differential, since both conditions can cause manic symptoms. The origin of mania should be delineated through a detailed neurological exam, neuroimaging, and thorough patient-family psychiatric history for appropriate clinical treatment.


Assuntos
Transtorno Bipolar/psicologia , Esclerose Múltipla/psicologia , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Pessoa de Meia-Idade , Risperidona/uso terapêutico
3.
Ann Biol Clin (Paris) ; 78(4): 449-453, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618565

RESUMO

Nephrogenic diabetes insipidus due to the inability of the kidneys to concentrate urine is frequently observed during lithium therapy. Lithium concentrates into principal cells in collecting ducts in the kidney and downregulates aquaporin 2 expression, which reduces renal reabsorption of water. This disease is characterized by polyuria - polydipsia leading to intracellular dehydration and hypernatremia. Water deprivation test is performed to confirm insipidus diabetes. The desmopressin permits to distinguish nephrogenic from cranial insipidus diabetes. We report the case of a 64 years old women who presented with global dehydration and severe hypernatremia. Four years ago, she was hospitalized for nephrogenic diabetes insipidus related to a self-induced lithium intoxication. Persistent nephrogenic insipidus diabetes after cessation of lithium therapy are described in literature, and this hypothesis may be consistent with this case report.


Assuntos
Diabetes Insípido Nefrogênico/induzido quimicamente , Compostos de Lítio/efeitos adversos , Sódio/efeitos adversos , Água/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Desidratação/diagnóstico , Desidratação/etiologia , Feminino , Humanos , Compostos de Lítio/envenenamento , Compostos de Lítio/uso terapêutico , Pessoa de Meia-Idade , Intoxicação por Água/complicações , Intoxicação por Água/diagnóstico
4.
Acta Med Port ; 33(10): 693-702, 2020 Oct 01.
Artigo em Português | MEDLINE | ID: mdl-32705981

RESUMO

INTRODUCTION: The COVID-19 pandemic is a particularly relevant threat to mentally ill patients, and it constitutes a new challenge for health care providers. To the best of our knowledge, there is not any embracing published review about the use of psychotropic drugs during the COVID-19 pandemic. MATERIALS AND METHODS: Non-systematic literature review. A search in the PubMed database was performed, with the terms 'psychotropic drugs', 'COVID-19', 'psychiatry' and 'pandemic'. Consensus and clinical guidelines about psychotropic drugs and COVID-19 approach, published by scientific societies, governmental entities and drug regulatory agencies were included. RESULTS AND DISCUSSION: We present the recommendations about the use of psychotropic drugs during the COVID-19 pandemic, in the outpatient and inpatient settings. The treatment of affective bipolar disorder and schizophrenia have now added increased difficulties. Some psychotropic drugs interfere with the pathophysiology of the novel coronavirus infection and they could interact with the drugs used in the treatment of COVID-19. Some patients will need pharmacological interventions due to the presence of delirium. Smoking cessation changes the serum levels of some psychotropic drugs and may influence their use. CONCLUSION: The COVID-19 pandemic has created new challenges in clinical practice. Psychiatric patients are a vulnerable population and often a careful clinical, laboratorial and electrocardiographic evaluation may be needed, particularly in those diagnosed with COVID-19. The regular treatment of mentally ill patients with COVID-19 presents increased complexity.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transtornos Mentais/tratamento farmacológico , Pneumonia Viral/epidemiologia , Psicotrópicos/uso terapêutico , Antivirais/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Regulação da Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/fisiologia , Buprenorfina/efeitos adversos , Buprenorfina/uso terapêutico , Clozapina/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Preparações de Ação Retardada/uso terapêutico , Interações Medicamentosas , Hospitalização , Humanos , Compostos de Lítio/uso terapêutico , Transtornos Mentais/complicações , Metadona/efeitos adversos , Metadona/uso terapêutico , Antagonistas de Entorpecentes/efeitos adversos , Antagonistas de Entorpecentes/uso terapêutico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Ácido Valproico/uso terapêutico
5.
Aging (Albany NY) ; 12(11): 10035-10040, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534451

RESUMO

Cell senescence is a process that causes growth arrest and the release of a senescence associated secretory phenotype (SASP), characterized by secretion of chemokines, cytokines, cell growth factors and metalloproteases, leading to a tissue condition that may precipitate cancers and neurodegenerative processes. With the recent pandemic of coronavirus, senolytic drugs are being considered as possible therapeutic tools to reduce the virulence of SARS-CoV-2. In the last few years, our research group showed that lithium carbonate at microdose levels was able to stabilize memory and change neuropathological characteristics of Alzheimer's disease (AD). In the present work, we present evidence that low-dose lithium can reduce the SASP of human iPSCs-derived astrocytes following acute treatment, suggesting that microdose lithium could protect cells from senescence and development of aging-related conditions. With the present findings, a perspective of the potential use of low-dose lithium in old patients from the "high risk group" for COVID-19 (with hypertension, diabetes and chronic obstructive pulmonary disease) is presented.


Assuntos
Astrócitos/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Humanos , Pandemias
6.
Neuron ; 106(5): 715-726, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32497508

RESUMO

Ketamine exerts rapid antidepressant action in depressed and treatment-resistant depressed patients within hours. At the same time, ketamine elicits a unique form of functional synaptic plasticity that shares several attributes and molecular mechanisms with well-characterized forms of homeostatic synaptic scaling. Lithium is a widely used mood stabilizer also proposed to act via synaptic scaling for its antimanic effects. Several studies to date have identified specific forms of homeostatic synaptic plasticity that are elicited by these drugs used to treat neuropsychiatric disorders. In the last two decades, extensive work on homeostatic synaptic plasticity mechanisms have shown that they diverge from classical synaptic plasticity mechanisms that process and store information and thus present a novel avenue for synaptic regulation with limited direct interference with cognitive processes. In this review, we discuss the intersection of the findings from neuropsychiatric treatments and homeostatic plasticity studies to highlight a potentially wider paradigm for treatment advance.


Assuntos
Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Homeostase/efeitos dos fármacos , Ketamina/farmacologia , Compostos de Lítio/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Animais , Antimaníacos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Humanos , Ketamina/uso terapêutico , Compostos de Lítio/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Sinapses/efeitos dos fármacos
7.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(3. Vyp. 2): 29-32, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32307427

RESUMO

INTRODUCTION: Ischemic stroke is one of the most severe neurological pathologies with high mortality and disability. In this connection, the development and study of new drugs for the prevention and treatment of stroke is an extremely important task. A new approach to neuroprotection is the use of lithium salts with antioxidant activity. AIM: To study the cerebroprotective effect of lithium ascorbate on a rat model of ischemic stroke. MATERIAL AND METHODS: Test samples of lithium ascorbate were synthesized ex tempore for an experiment using reagents of ACS qualification (Sigma-Aldrich). The ischemic stroke model was realized using the filament occlusion of the middle cerebral artery in rats of the Sprague Dawley line according to standardized procedure. Neurological examination of the animals, histological study of brain tissue with staining of brain sections, and calculating the volume of cerebral infarction were performed. RESULTS AND CONCLUSION: There is a significant cerebroprotective effect of lithium ascorbate expressed in a multiple decrease in the volume of the zone of cerebral infarction (by 75% of the control group indicator) and the absence of mortality in the experimental group of animals. Newly discovered distinct anti-stroke effect of lithium ascorbate in combination with low toxicity could be considered promising for further clinical studies and practical application in neurology.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/prevenção & controle , Modelos Animais de Doenças , Compostos de Lítio/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Animais , Isquemia Encefálica/patologia , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/patologia , Compostos de Lítio/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/patologia
8.
Psychiatry Res ; 286: 112865, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32114208

RESUMO

Bipolar disorder (BD) may be associated with accelerated cellular aging. However, previous studies on telomere length (TL), an important biomarker of cellular aging, have yielded mixed results in BD. We aimed to evaluate the hypothesis that BD is associated with telomere shortening and whether this is counteracted by long-term lithium treatment. We also sought to determine whether long-term lithium treatment is associated with increased expression of telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. We determined TL and TERT expression in 100 BD I patients and 100 healthy controls. We also genotyped three single nucleotide polymorphisms associated with TL. TERT expression was significantly increased in BD I patients currently on lithium treatment. TERT expression was also significantly positively correlated with duration of lithium treatment in patients treated for 24 months or more. However, we did not find any significant effect of lithium treatment on TL. Neither did we find significant differences in TL between BD patients and controls. We suggest that long-term lithium treatment is associated with an increase in the expression of TERT. We hypothesize that an increase in TERT expression may contribute to lithium's mood stabilizing and neuroprotective properties by improving mitochondrial function and decreasing oxidative stress.


Assuntos
Envelhecimento/metabolismo , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Senescência Celular/genética , Compostos de Lítio/uso terapêutico , Lítio/uso terapêutico , Telomerase/metabolismo , Adulto , Envelhecimento/genética , Transtorno Bipolar/sangue , Senescência Celular/efeitos dos fármacos , Feminino , Humanos , Compostos de Lítio/farmacologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real , Telomerase/efeitos dos fármacos , Telomerase/genética , Telômero/efeitos dos fármacos , Telômero/genética , Telômero/metabolismo , Homeostase do Telômero/genética , Encurtamento do Telômero/efeitos dos fármacos , Encurtamento do Telômero/genética
9.
Psychiatr Clin North Am ; 43(1): 95-111, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008691

RESUMO

Pediatric bipolar disorder (PBD) is a severe and chronic illness. The occurrence of mixed symptoms might add further risk of recurrence of treatment resistance and suicidality. Early recognition and treatment of mixed symptoms might prevent illness progression and development of suicide attempts. This article provides an update on the epidemiology, clinical profile, and treatment of youth with PBD with mixed states. Mixed states in PBD are characterized by higher rates of suicide and more chronic symptoms, and are associated with younger age of onset and greater comorbidity. A careful assessment for mixed states using standardized criteria is essential.


Assuntos
Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Adolescente , Criança , Pré-Escolar , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Masculino , Tentativa de Suicídio , Adulto Jovem
10.
Sci Rep ; 10(1): 647, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959776

RESUMO

Accumulating evidence suggests AKT1 and DRD2-AKT-GSK3 signaling involvement in schizophrenia. AKT1 activity is also required for lithium, a GSK3 inhibitor, to modulate mood-related behaviors. Notably, GSK3 inhibitor significantly alleviates behavioral deficits in Akt1-/- female mice, whereas typical/atypical antipsychotics have no effect. In agreement with adjunctive therapy with lithium in treating schizophrenia, our data mining indicated that the average utilization rates of lithium in the Taiwan National Health Insurance Research Database from 2002 to 2013 are 10.9% and 6.63% in inpatients and outpatients with schizophrenia, respectively. Given that lithium is commonly used in clinical practice, it is of great interest to evaluate the effect of lithium on alleviating Akt1-related deficits. Taking advantage of Akt1+/- mice to mimic genetic deficiency in patients, behavioral impairments were replicated in female Akt1+/- mice but were alleviated by subchronic lithium treatment for 13 days. Lithium also effectively alleviated the observed reduction in phosphorylated GSK3α/ß expression in the brains of Akt1+/- mice. Furthermore, inhibition of Akt expression using an Akt1/2 inhibitor significantly reduced neurite length in P19 cells and primary hippocampal cell cultures, which was also ameliorated by lithium. Collectively, our findings implied the therapeutic potential of lithium and the importance of the AKT1-GSK3 signaling pathway.


Assuntos
Bases de Dados Factuais , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Seguro Saúde , Compostos de Lítio/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Transdução de Sinais , Adolescente , Adulto , Idoso , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Humanos , Compostos de Lítio/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Taiwan , Adulto Jovem
11.
PLoS One ; 15(1): e0227217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923220

RESUMO

BACKGROUND: Although mood stabilizers such as lithium (LIT), valproate (VAL), and lamotrigine (LMT) appear to be efficacious treatments for bipolar disorder (BD) in research settings, the long-term response to these mood stabilizers in clinical practice is highly variable among individuals. Thus, the present study examined the characteristics associated with good or insufficient responses to long-term treatment with LIT, VAL, or LMT for BD. METHODS: This study retrospectively analyzed the medical records of patients who visited an outpatient clinic with a diagnosis of BD I or II. Data from patients who were treated with one of three mood stabilizing medications (LIT, VAL, or LMT) for more than 6 months were selected, and the long-term treatment responses were evaluated using the Alda scale. For the purposes of this study, two response categories were formed: insufficient response (ISR), including non-response or poor response (Alda total score ≤ 6), and good response (GR; Alda total score ≥ 7). RESULTS: Of the 645 patients included in the present study, 172 were prescribed LIT, 320 were prescribed VAL, and 153 were prescribed LMT for at least 6 months. A binary logistic regression analysis revealed that a diagnosis of BD II (odds ratio [OR], 8.868; 95% confidence interval [CI], 1.123-70.046; p = 0.038), comorbid alcohol/substance use disorder (OR, 4.238; 95% CI, 1.154-15.566; p = 0.030), and a history of mixed episodes (OR, 4.363; 95% CI, 1.191-15.985; p = 0.026) were significant predictors of LIT-ISR. Additionally, a depressive-predominant polarity significantly predicted LMT-GR (OR, 8.586; 95% CI, 2.767-26.644; p < 0.001). CONCLUSION: The present findings demonstrated that patients with a diagnosis of BD II, a comorbid alcohol/substance problem, or a history of mixed episodes were not likely to respond to LIT treatment. Additionally, LMT might be a better treatment choice for patients with a depressive-predominant polarity.


Assuntos
Alcoolismo/epidemiologia , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Lamotrigina/uso terapêutico , Compostos de Lítio/uso terapêutico , Ácido Valproico/uso terapêutico , Adulto , Comorbidade , Feminino , Seguimentos , Humanos , Compostos de Lítio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Seul/epidemiologia , Resultado do Tratamento
12.
J Affect Disord ; 260: 361-365, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539671

RESUMO

OBJECTIVE: Misdiagnosis is common in bipolar disorder and disproportionally affects racial and ethnic minorities. There is interest in better understanding the contribution of differential symptomatic illness presentation to misdiagnosis. METHODS: Utilizing the Genetic Association Information Network (GAIN) public database, this study compared clinical phenomenology between bipolar patients of African vs European ancestry (AA = 415 vs EA = 480). The Diagnostic Interview for Genetic Studies (DIGS) was utilized to evaluate symptom endorsement contributing to diagnostic confirmation of bipolar I disorder (BPI) and lifetime medication use. RESULTS: Elevated/euphoric mood was less endorsed in AA vs EA participants (p = 0.03). During the most severe episode of mania, AA participants, in comparison to EA participants, had a lower sum of manic symptoms (p = 0.006) and a higher rate of hallucinations (p = 0.01). During lifetime psychosis, AA participants, in comparison to EA participants, had a higher lifetime sum of delusions (p = 0.01) and hallucinations (p < 0.0001). AA participants reported lower use of lithium (p < 0.0001) and mood stabilizing anticonvulsants (p = 0.0003). CONCLUSIONS: The differential rate of manic and psychotic symptom endorsement from a semi-structured diagnostic interview may represent differential illness presentation based on biological differences or racial or study biases (e.g. ascertainment). Increased minority recruitment in bipolar research is therefore a necessary future direction. LIMITATIONS: Recall and interviewer bias may affect study results, but are likely diminished by the alignment of symptom endorsement and medication use.


Assuntos
Grupo com Ancestrais do Continente Africano/psicologia , Antimaníacos/uso terapêutico , Transtorno Bipolar/etnologia , Grupo com Ancestrais do Continente Europeu/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Adulto , Anticonvulsivantes/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Bases de Dados Factuais , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estados Unidos
14.
Am J Psychiatry ; 177(1): 76-92, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31623458

RESUMO

OBJECTIVE: Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring. METHODS: The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018. RESULTS: Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels <0.64 mEq/L and dosages <600 mg/day had more reactive newborns without an increased risk of cardiac malformations. CONCLUSIONS: The risk associated with lithium exposure at any time during pregnancy is low, and the risk is higher for first-trimester or higher-dosage exposure. Ideally, pregnancy should be planned during remission from bipolar disorder and lithium prescribed within the lowest therapeutic range throughout pregnancy, particularly during the first trimester and the days immediately preceding delivery, balancing the safety and efficacy profile for the individual patient.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Aborto Espontâneo/epidemiologia , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/efeitos adversos , Compostos de Lítio/uso terapêutico , Transtorno Bipolar/sangue , Feminino , Humanos , Compostos de Lítio/sangue , Período Pós-Parto/efeitos dos fármacos , Gravidez , Resultado do Tratamento
15.
Curr Drug Res Rev ; 11(2): 85-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31875781

RESUMO

BACKGROUND: The effectiveness of lithium salts in neuropsychiatric disorders such as bipolar disorder, Alzheimer's disease, and treatment-resistant depression has been documented in an extensive scientific literature. Lithium inhibits inositol monophosphatase, inositol polyphosphate 1- phosphatase, and glycogen synthase kinase-3 and decreases expression level of tryptophan hydroxylase 2, conceivably underlying the mood stabilizing effects of lithium, as well as procognitive and neuroprotective effects. However, the exact molecular mechanisms of action of lithium on mood stabilizing and pro-cognitive effects in humans are still largely unknown. OBJECTIVE: On the basis of the known aspects of lithium pharmacology, this review will discuss the possible mechanisms underlying the therapeutic effects of lithium on positive symptoms of methamphetamine abuse and dependence. CONCLUSION: It is possible that lithium treatment reduces the amount of newly synthesized phosphatidylinositol, potentially preventing or reversing neuroadaptations contributing to behavioral sensitization induced by methamphetamine. In addition, it is suggested that exposure to repeated doses of methamphetamine induces hyperactivation of glycogen synthase kinase-3ß in the nucleus accumbens and in dorsal hippocampus, resulting in a long-term alterations in synaptic plasticity underlying behavioral sensitization as well as other behavioral deficits in memory-related behavior. Therefore it is clear that glycogen synthase kinase-3ß inhibitors can be considered as a potential candidate for the treatment of methamphetamine abuse and dependence.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Estimulantes do Sistema Nervoso Central , Compostos de Lítio/farmacologia , Compostos de Lítio/uso terapêutico , Metanfetamina , Animais , Antimaníacos/farmacologia , Antimaníacos/uso terapêutico , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Humanos
16.
BMJ Case Rep ; 12(11)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678916

RESUMO

A young man with neuropsychiatric problems has a small 22q13.33 duplication. We suggest this causes his condition. His disorder may represent a 22q13.33 behavioural phenotype. In childhood, he was diagnosed with mild intellectual disability. He was later diagnosed with Tourette syndrome, atypical autism spectrum disorder and bipolar disorder. Lithium seems effective in treating his affective symptoms. He has mild dysmorphic features, full lips and protruding ears. An array comparative genomic hybridisation showed a 300 kb duplication. The duplication harbours several genes, notably SH3 and multiple ankyrin repeat domain 3 (SHANK 3). The small size helps focus on a critical region for a 22q13.33 duplication syndrome. Mutations, deletions and duplications should be kept in mind as causes of neuropsychiatric disorders, especially in a patient with dysmorphic traits.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno Bipolar/diagnóstico , Transtornos Cromossômicos/diagnóstico , Deficiência Intelectual/diagnóstico , Síndrome de Tourette/diagnóstico , Antimaníacos/uso terapêutico , Transtorno do Espectro Autista/complicações , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Deleção Cromossômica , Transtornos Cromossômicos/complicações , Cromossomos Humanos Par 22 , Humanos , Deficiência Intelectual/complicações , Compostos de Lítio/uso terapêutico , Masculino , Proteínas do Tecido Nervoso/genética , Síndrome de Tourette/complicações , Síndrome de Tourette/tratamento farmacológico , Adulto Jovem
17.
Curr Psychiatry Rep ; 21(11): 114, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701245

RESUMO

PURPOSE OF REVIEW: Despite being recognized as a first-line treatment for bipolar disorder, there is still inconsistent use of lithium in perinatal populations. This article will review data regarding lithium use during the peripartum and provide management recommendations for general psychiatric clinicians. RECENT FINDINGS: In contrast to prior data, recent studies indicate that lithium use in pregnancy is associated with either no increased malformations risk or a small increase in risk for cardiac malformations including Ebstein's anomaly. Limited data also show no significant effect on obstetric or neurodevelopmental outcomes. Data regarding infant lithium exposure via breastmilk remains limited. Lithium is currently under-prescribed and is an important treatment for women with bipolar disorder in pregnancy and the postpartum. Clinicians must weigh the risk of lithium treatment versus the risk of withholding or changing lithium treatment when managing bipolar disorder in this population.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Lítio/uso terapêutico , Período Pós-Parto/efeitos dos fármacos , Complicações na Gravidez/psicologia , Feminino , Humanos , Lactente , Lítio/efeitos adversos , Compostos de Lítio/efeitos adversos , Período Pós-Parto/psicologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Medição de Risco , Resultado do Tratamento
18.
Presse Med ; 48(11 Pt 1): 1306-1318, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31732367

RESUMO

CONTEXT: Bipolar disorder (BD) is a severe and recurrent mood disorder. It is characterized by episodic changes in mood and energy/activity levels that are increased during mania/hypomania or decreased during depression. Recurrent mania (RM) is a mood disorder, which would be defined by at least two manic/hypomanic without depressive episodes. Despite a rich body of clinical descriptions, RM is still not integrated into the latest editions of disease classifications and continues to be subsumed under BD in clinical practice. OBJECTIVES: We conducted a systematic review of the literature to pool data about RM prevalence within BD groups, identify differences between RM and BD and develop reliable knowledge about specificities of RM. Furthermore, we sought to identify the methodological bias inherent to RM studies. METHOD: Relevant publications were identified by a systematic search of PubMed, Embase, ScienceDirect and PsychInfo databases according to PRISMA criteria, with no limitation of date. The following MESH terms were used: (mania OR manic) AND (unipolar) NOT (depress*) OR ("unipolar mania" OR "unipolar manic" NOT "depress*"). RESULTS: Twenty-three (23) of 186identified studies met eligibility criteria for our systematic review. The total sample included 1118RM subjects among 4796BD subjects. The weighted mean of RM prevalence was 23.2%. Compared to BD, RM was characterized by a predominance of men, an earlier age at illness onset, less rapid cycles and seasonal variations, longer manic episodes, less specific clinical features (suicide attempts, anxious disorders, catatonic symptoms, irritability, hyperactivity, racing thoughts), less family history of depression, more addictive comorbidities and worse response to lithium prophylaxis (P<0.05). However, many studies failed to replicate these significant differences. LIMITS: RM studies were mainly retrospective. The major bias of RM studies were the lack of consensus on the defining criteria for RM and the risk of unreported depressive episodes, both in charts that were reviewed in retrospective studies and in prospective studies with insufficient follow-up duration. CONCLUSION: Although the literature on RM remains sparse, many authors agree that RM should be distinguished from BD. RM would concern almost 1 in 4 BD patients. Furthermore, several clinical variables could differentiate this mood disease from BD and may orient the specific therapeutic choice. However, clinical criteria are still not reliable enough to make a diagnosis of RM. Further studies are required to replicate the results of existing studies and to adjust for the effect of methodological biases.


Assuntos
Transtorno Bipolar/diagnóstico , Depressão/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Depressão/psicologia , Diagnóstico Diferencial , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Masculino , Prevalência , Estudos Prospectivos , Recidiva , Estudos Retrospectivos
19.
Transl Psychiatry ; 9(1): 297, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723123

RESUMO

The present study intends to investigate the effect of lithium (Li) and celecoxib (Cel) coadministration on the behavioral status and oxidative stress parameters in a rat model of mania induced by dextroamphetamine (d-AMPH). Male Wistar rats were treated with d-AMPH or saline (Sal) for 14 days; on the 8th day of treatment, rats received lithium (Li), celecoxib (Cel), Li plus Cel, or water until day 14. Levels of oxidative stress parameters were evaluated in the serum, frontal cortex, and hippocampus. d-AMPH administration induced hyperlocomotion in rats, which was significantly reversed by Li and Cel coadministration. In addition, d-AMPH administration induced damage to proteins and lipids in the frontal cortex and hippocampus of rats. All these impairments were reversed by treatment with Li and/or Cel, in a way dependent on cerebral area and biochemical analysis. Li and Cel coadministration reversed the d-AMPH-induced decrease in catalase activity in cerebral structures. The activity of glutathione peroxidase was decreased in the frontal cortex of animals receiving d-AMPH, and treatment with Li, Cel, or a combination thereof reversed this alteration in this structure. Overall, data indicate hyperlocomotion and alteration in oxidative stress biomarkers in the cerebral structures of rats receiving d-AMPH. Li and Cel coadministration can mitigate these modifications, comprising a potential novel approach for BD therapy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antimaníacos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Transtorno Bipolar/tratamento farmacológico , Celecoxib/uso terapêutico , Compostos de Lítio/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antimaníacos/administração & dosagem , Transtorno Bipolar/induzido quimicamente , Celecoxib/administração & dosagem , Dextroanfetamina/administração & dosagem , Modelos Animais de Doenças , Dopamina/metabolismo , Quimioterapia Combinada , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Compostos de Lítio/administração & dosagem , Masculino , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
20.
Turk Psikiyatri Derg ; 30(3): 163-171, 2019.
Artigo em Turco | MEDLINE | ID: mdl-31613975

RESUMO

OBJECTIVE: Despite lithium associated hyperparathyroidism (LAH) can lead to many complications, little notice has been paid to this sideeffect. The aim of this study was to investigate the effects of lithium on calcium and parathyroid hormone levels and the relation between lithium use and thyroid diseases. METHOD: This cross-sectional study was carried out with 87 lithiumtreated patients and 65 volunteers who had a similar age and gender distribution with the lithium group. Serum levels of corrected calcium, intact parathormone, phosphorus, magnesium, alkaline phosphatase, free thyroxine, thyroid stimulating hormone, thyroid autoantibodies and creatinine were assessed, and also, thyroid and parathyroid ultrasonography was conducted. Further detailed investigations were made depending on the elevation of the initially measured calcium and/ or parathormone levels. RESULTS: Median values of serum levels of the corrected calcium and the intact parathormone were significantly higher in the lithium group. Calcium levels had a mild correlation with the duration of lithium treatment. In the first assessment, while all control individuals had values within the normal reference range, 11 lithium-treated patients had corrected calcium and/or intact parathormone levels above the normal reference levels. All of the five patients, who were diagnosed with LAH after further investigation, were also diagnosed with a thyroid disorder. CONCLUSION: These results demonstrate that lithium treatment has a relationship with calcium and parathormone levels. The 5.7% prevalence of LAH and potential life-threatening conditions associated with LAH necessitates the use of available low-cost METHODS to monitor blood calcium levels of lithium-treated patients for early diagnosis.


Assuntos
Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Cálcio/sangue , Compostos de Lítio/farmacologia , Hormônio Paratireóideo/sangue , Adolescente , Adulto , Idoso , Antimaníacos/uso terapêutico , Transtorno Bipolar/sangue , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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