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1.
Psychiatr Danub ; 31(Suppl 3): 595-603, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488797

RESUMO

BACKGROUND: Bipolar disorder is a mental illness characterised by periods of elevated mood alternating with periods of depression. Long-term relapse prevention in bipolar disorder is challenging, with a significant number of patients relapsing following the initial stabilisation of mood. Initial treatment of the condition is complex and usually occurs in secondary care. Whilst there is no known cure for bipolar disorder, several therapies have been found to be effective in both managing acute episodes and sustaining long-term remission. The key pharmacological therapies in bipolar disorder are lithium salts, antiepileptics and antipsychotics and these will be the focus of this review. AIM: This review seeks to outline the key common pharmacological therapies used in the treatment and relapse prevention of this condition. METHODS: A MEDLINE search was performed, and the available literature was subsequently analysed, including meta-analyses, reviews and original clinical trials. RESULTS: Management strategies can be subdivided into treating acute presentations of mania and depression and maintaining long-term remission. The extensive side effect profile of several antipsychotics means that there are certain patient groups for whom they may be intolerable or contraindicated. Lithium emerges as a highly efficacious maintenance therapy but retains the burden of therapeutic drug monitoring. Antiepileptics play a crucial role in maintaining remission but are linked to serious, albeit rare, side effects. CONCLUSION: Despite the efficacy of the medications discussed in this article, their underlying mechanisms of action remain to be fully elucidated. Nonetheless, these key therapies continue to be essential tools in the management of bipolar disorder.


Assuntos
Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Antimaníacos/uso terapêutico , Humanos
3.
Acta Neuropsychiatr ; 31(4): 230-234, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31169098

RESUMO

BACKGROUND: Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear. METHODS: Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response. RESULTS: Compared to participants with WBC counts of 4.5-10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses. CONCLUSIONS: An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar , Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Adulto , Afeto , Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/imunologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
4.
Expert Opin Pharmacother ; 20(13): 1575-1588, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150304

RESUMO

Introduction: Mood stabilizers and antipsychotics have been demonstrated to be effective in Bipolar Disorder, with lithium as the gold standard. However, the presence of adverse events and treatment-resistance is still a relevant issue. To this respect, the use of brain stimulation techniques may be considered as an augmentation strategy, with both Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) having shown some level of efficacy in bipolar patients although clinical trials are still not sufficient to draw any conclusion. Areas covered: The authors have conducted a systematic review of the literature, in order to evaluate the role of mood stabilizers on neural activity and cortical excitability. Furthermore, the article reviews neuromodulation techniques and highlights the potential of integrating pharmacological first-line therapies with these techniques to treat BD patients. Expert opinion: The combination of neuromodulation techniques and available pharmacotherapies is a valuable opportunity which is not undermined by specific effects on cortical excitability and could improve BD patient outcome. Neurostimulation techniques may be considered safer than antidepressant treatments in BD, with a lower level of manic switches and may represent a new treatment strategy in BD depressive episodes.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Terapia Combinada , Excitabilidade Cortical/efeitos dos fármacos , Humanos , Compostos de Lítio/uso terapêutico
5.
Expert Opin Pharmacother ; 20(12): 1457-1470, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31112441

RESUMO

Introduction: ADHD is characterized by a developmentally inappropriate level of inattentiveness, impulsivity and/or hyperactivity. In adults, the disorder is frequently accompanied by Emotional Dysregulation (ED), associated to a variety of related psychiatric comorbidities, complicating its recognition and treatment management. Areas covered: This paper reviews randomized active comparator-controlled or placebo-controlled trials evaluating the use of pharmacotherapy in adults with ADHD and ED, other neurodevelopmental disorders, Bipolar Disorder (BD) and Anxiety Disorders (ADs). When controlled data are unavailable, the authors have included open-label and observational studies. Expert opinion: ED in adult patients with ADHD is a very common and impairing problem that can be treated with stimulants or atomoxetine. ADHD studies in adults with other neurodevelopment disorders are scarce; stimulants seem to be the most effective and safe drugs in treating ADHD symptoms, without worsening the core features of other neurodevelopmental disorders. In patients with ADHD and comorbid BD, the treatment of BD alone may result in residual symptoms of ADHD. Patients should be treated hierarchically: BD should be treated first, while ADHD should be treated combining ADHD medications and mood stabilizers after mood stabilization. The available evidence for treating patients with ADHD and comorbid ADs in adults supports the idea of an anti-anxiety/ADHD-specific treatment association.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Tratamento Farmacológico/tendências , Drogas em Investigação/uso terapêutico , Adulto , Antimaníacos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/epidemiologia , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Comorbidade , Tratamento Farmacológico/métodos , Humanos , Estudos Observacionais como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Terapias em Estudo/métodos , Terapias em Estudo/tendências
6.
Clin Perinatol ; 46(2): 215-234, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010557

RESUMO

Risks, benefits, alternatives, and appropriateness of psychotropic medications, including risks of no treatment, are discussed for antidepressants, mood-stabilizing medications, anxiolytic/sedative hypnotic medications, stimulants, and medication-assisted treatment of substance use disorders. Early screening, diagnosis, and intervention prior to and/or during pregnancy often reduce morbidity and mortality of mental health disorders for mothers and infants.


Assuntos
Transtornos Mentais/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Psicotrópicos/uso terapêutico , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Feminino , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Humanos , Troca Materno-Fetal , Transtornos Relacionados ao Uso de Opioides , Síndrome da Persistência do Padrão de Circulação Fetal/epidemiologia , Hemorragia Pós-Parto/epidemiologia , Gravidez , Transtornos Psicóticos/tratamento farmacológico , Índice de Gravidade de Doença , Síndrome de Abstinência a Substâncias , Transtornos Relacionados ao Uso de Substâncias/terapia
7.
Metabolism ; 95: 65-76, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954559

RESUMO

Changes of sphingolipid metabolism were suggested to contribute to the patho-etiology of major depression (MD) and bipolar disorder (BD). In a pilot study we assessed if lipid allostasis manifested in pathological plasma concentrations of bioactive lipids i.e. endocannabinoids, sphingolipids, ceramides, and lysophosphatidic acids. METHODS: Targeted and untargeted lipidomic analyses were performed according to GLP guidelines in 67 patients with unipolar or bipolar disorders (20-67 years, 36 male, 31 female) and 405 healthy controls (18-79 years, 142 m, 263 f), who were matched according to gender, age and body mass index. Multivariate analyses were used to identify major components, which accounted for the variance between groups and were able to predict group membership. RESULTS: Differences between MD and BP patients versus controls mainly originated from ceramides and their hexosyl-metabolites (C16Cer, C18Cer, C20Cer, C22Cer, C24Cer and C24:1Cer; C24:1GluCer, C24LacCer), which were strongly increased, particularly in male patients. Ceramide levels were neither associated with the current episode, nor with the therapeutic improvement of the Montgomery Åsberg Depression Rating Scale (MARDS). However, long-chain ceramides were linearly associated with age, stronger in patients than controls, and with high plasma levels of diacyl- and triacylglycerols. Patients receiving antidepressants had higher ceramide levels than patients not taking these drugs. There was no such association with lithium or antipsychotics except for olanzapine. CONCLUSION: Our data suggest that high plasma ceramides in patients with major depression and bipolar disorder are indicative of a high metabolic burden, likely aggravated by certain medications.


Assuntos
Transtorno Bipolar/metabolismo , Ceramidas/metabolismo , Transtorno Depressivo Maior/metabolismo , Metabolismo dos Lipídeos/genética , Adolescente , Adulto , Fatores Etários , Idoso , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Antimaníacos/efeitos adversos , Antimaníacos/uso terapêutico , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Índice de Massa Corporal , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Diglicerídeos/metabolismo , Feminino , Humanos , Lítio/efeitos adversos , Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Escalas de Graduação Psiquiátrica , Caracteres Sexuais , Triglicerídeos/metabolismo , Adulto Jovem
8.
Expert Opin Pharmacother ; 20(5): 571-583, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30702354

RESUMO

INTRODUCTION: Conduct disorder (CD) is a common mental health disorder of childhood and adolescence. CD's complexity, with its heterogenous clinical manifestations and overlapping comorbidities makes the application of evidence-based management approaches challenging. This article aims to combine a systematic review of the available literature, with a consensus opinion from both child and adolescent psychiatrists and developmental pediatricians on the clinical and pharmacological management of children and adolescents with conduct disorder (CD). AREAS COVERED: The authors review the CD population and provide a systematic review and meta-analysis of the effectiveness and safety of pharmacotherapies using preferred reporting items for systematic review and meta-analysis (PRISMA) and strength of evidence recommendation taxonomy (SORT) guidelines. The authors then provide an expert clinical opinion for the use of different pharmacotherapies to address aggressive and disruptive behavior in children. EXPERT OPINION: Atypical antipsychotics (e.g. risperidone) demonstrate evidence for efficacy in CD. Other pharmacotherapies (e.g. mood stabilizers, anticonvulsants, psychostimulants and selective norepinephrine reuptake inhibitors) have a low level of evidence for CD alone, however, can sometimes be effective in managing the symptoms of CD when other psychiatric disorders are also present.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno da Conduta/tratamento farmacológico , Adolescente , Agressão/efeitos dos fármacos , Anticonvulsivantes/uso terapêutico , Antimaníacos/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Humanos , Risperidona/uso terapêutico
9.
J Affect Disord ; 249: 15-19, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30743017

RESUMO

BACKGROUND: Apparent comorbidity between bipolar disorder (BD) and obsessive-compulsive disorder (OCD) is a common condition in psychiatry, but treatment of BD-OCD remains a clinical challenge. Although serotonin reuptake inhibitors (SRIs) are the first line treatment for OCD, they can induce mood instability in BD. An optimal treatment approach remains to be defined. METHODS: A systematic review was conducted on aripiprazole augmentation in treating comorbid BD-OCD patients. Relevant papers published through August 31st 2018 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS: Aripiprazole augmentation to mood stabilizers (lithium carbonate, valproate), even at low doses (10-15 mg/day), helped to achieve significant remission in affective and obsessive-compulsive symptoms. Aripiprazole was generally safe and well tolerated. LIMITATIONS: Most studies are case reports. Enrolment of subjects mainly from outpatient specialty units might have introduced selection bias and limited community-wide generalizability. CONCLUSIONS: Keeping in mind scantiness and heterogeneity of the available literature, the best interpretation of the available evidence appears to be that aripiprazole augmentation to mood stabilizers, even at low doses, is effective in BD-OCD patients.


Assuntos
Aripiprazol/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Antimaníacos/uso terapêutico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Comorbidade , Humanos , Carbonato de Lítio/uso terapêutico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/psicologia
10.
J Affect Disord ; 245: 812-818, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699864

RESUMO

BACKGROUND: Divalproex has become the most prevalent mood stabilizer for bipolar disorder. However, little is known its effects in the prevention of suicide in patients with bipolar disorder, and recent FDA announcement indicated an increased risk of suicidality when using anti-epileptic agents such as divalproex. The aim of this study is to investigate the effect of divalproex on suicide risk in patients with bipolar disorder. METHODS: A search strategy was used for the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov until June 13th, 2018. Peer-reviewed observationally clinical studies in humans, investigating the association of divalproex and suicidality in patients with bipolar disorder were included. A random-effects meta-analysis was implemented to calculate the relative risk (RR) and 95% confidence intervals (CIs) for suicidality among patients receiving divalproex and those without. RESULTS: Total 6 studies were included in the final meta-analysis. There was no significant difference in the incidence rates (reported as [RR]; 95% CI) of suicide attempts (0.921; 0.383-2.215) or completed suicides (0.607; 0.180-2.043) between participants receiving divalproex vs. no medication. There was no significant difference in the incidence rates of suicide attempts (0.815; 0.453-1.466) or completed suicides (1.009; 0.410-2.484) between participants receiving divalproex and carbamazepine. LIMITATIONS: The significantly heterogeneous sample sources and study design amount the included trials. CONCLUSIONS: Treatment with divalproex did not reduce or increase the incidence of suicide-related events in patients with bipolar disorder.


Assuntos
Antimaníacos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Internacionalidade , Estudos Observacionais como Assunto , Tentativa de Suicídio/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Ácido Valproico/efeitos adversos , Antimaníacos/uso terapêutico , Humanos , Ácido Valproico/uso terapêutico
11.
J Affect Disord ; 245: 957-964, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699881

RESUMO

BACKGROUND: Objective of the present study was to conduct an 8-week double-blind, randomized, placebo-controlled trial to test the efficacy of pioglitazone in the treatment of bipolar depression. METHODS: 38 outpatients with bipolar disorder and current major depressive episode were randomized to pioglitazone (15-45 mg/day) or placebo. The use of concomitant mood stabilizers, antipsychotics, and antidepressants was permitted. The primary outcome measure was the 30-item Inventory of Depressive Symptomatology, Clinician Rated (IDS-C30) total score change from baseline to endpoint. Laboratory evaluations, including serum level of inflammatory and metabolic biomarkers, were conducted. RESULTS: 37 subjects were analyzed for efficacy (1 subject had no follow-up data). Mean reduction from baseline to week 8 in IDS-C30 score was-6.59 for pioglitazone and -11.63 for placebo. Mixed effects modeling indicated borderline statistically significant difference between the two groups (p = 0.056) in favor of placebo. On analysis of inflammatory and metabolic markers, a statistically significant negative correlation was noted between change in leptin levels and change in depression scores in the pioglitazone group (r = -0.61, p = 0.047) but not in the placebo group, the significance of which is unclear as the study failed to demonstrate antidepressant efficacy of pioglitazone over placebo. No serious adverse effects were reported, and pioglitazone was well-tolerated. LIMITATIONS: small sample size with inadequate power, concomitant use of other psychotropic medications, and lack of statistical adjustment for multiple testing. CONCLUSION: Current study does not support the antidepressant efficacy of pioglitazone in the treatment of bipolar depression. (240 words).


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Pioglitazona/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/psicologia , Depressão , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Australas Psychiatry ; 27(2): 125-128, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30763123

RESUMO

OBJECTIVES: To describe prescription of sodium valproate (SV) for bipolar mood disorder to potentially child-bearing women within one public mental health service and describe risks of fetal exposure, and safe prescribing practices among psychiatrists. METHODS: A 24-month retrospective chart review with descriptive analysis; narrative review of literature and guidelines. RESULTS: Review of 383 charts demonstrated prescription of valproate to 20% of 98 women aged 15-45, with little evidence of advice regarding risk and contraception. Robust evidence of teratogenic and neurodevelopmental risk underpins increased regulation, and recommendations that valproate not be prescribed to this cohort. CONCLUSIONS: The significant risks associated with SV oblige all prescribers to proactively access authoritative guidelines such as those published by the Centre of Perinatal Excellence.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Padrões de Prática Médica , Complicações na Gravidez/tratamento farmacológico , Teratogênios , Ácido Valproico/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Antimaníacos/efeitos adversos , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Gravidez , Complicações na Gravidez/psicologia , Fatores de Risco , Ácido Valproico/efeitos adversos
15.
Curr Psychiatry Rep ; 21(1): 3, 2019 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-30661128

RESUMO

PURPOSE OF REVIEW: This narrative review synthesized recent research related to obesity in adolescents with psychiatric disorders, with a focus on epidemiology, mechanisms, and weight management approaches. The paper reviews literature on depressive and anxiety disorders, bipolar disorder, and schizophrenia spectrum and other psychotic disorders. RECENT FINDINGS: Depression has a bidirectional relationship with obesity. Bipolar disorder and schizophrenia spectrum disorders, and their treatments, increase the risk of developing obesity. Mechanisms underlying this weight gain include lifestyle and environmental factors and psychiatric medications, though emerging evidence has also suggested the role of genetic and neuroendocrine processes. Evidence about the most effective treatments for obesity in adolescents with psychiatric disorders remains limited. Adolescents with psychiatric disorders are at high risk for obesity. Close monitoring for increases in weight and cardiometabolic risk factors with use of antipsychotic and mood-stabilizing medications is recommended. Clinical trials are needed that test the efficacy of weight management strategies for this population.


Assuntos
Transtornos de Ansiedade/complicações , Transtorno Bipolar/complicações , Transtorno Depressivo/complicações , Obesidade/induzido quimicamente , Obesidade/complicações , Esquizofrenia/complicações , Adolescente , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Humanos , Estilo de Vida , Fatores de Risco , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento , Ganho de Peso/efeitos dos fármacos
16.
Mol Psychiatry ; 24(2): 198-217, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29679069

RESUMO

We summarize evidence supporting contemporary pharmacological treatment of phases of BD, including: mania, depression, and long-term recurrences, emphasizing findings from randomized, controlled trials (RCTs). Effective treatment of acute or dysphoric mania is provided by modern antipsychotics, some anticonvulsants (divalproex and carbamazepine), and lithium salts. Treatment of BD-depression remains unsatisfactory but includes some modern antipsychotics (particularly lurasidone, olanzapine + fluoxetine, and quetiapine) and the anticonvulsant lamotrigine; value and safety of antidepressants remain controversial. Long-term prophylactic treatment relies on lithium, off-label use of valproate, and growing use of modern antipsychotics. Lithium has unique evidence of antisuicide effects. Methods of evaluating treatments for BD rely heavily on meta-analysis, which is convenient but with important limitations. Underdeveloped treatment for BD-depression may reflect an assumption that effects of antidepressants are similar in BD as in unipolar major depressive disorder. Effective prophylaxis of BD is limited by the efficacy of available treatments and incomplete adherence owing to adverse effects, costs, and lack of ongoing symptoms. Long-term treatment of BD also is limited by access to, and support of expert, comprehensive clinical programs. Pursuit of improved, rationally designed pharmacological treatments for BD, as for most psychiatric disorders, is fundamentally limited by lack of coherent pathophysiology or etiology.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Adulto , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Lítio/uso terapêutico , Compostos de Lítio/uso terapêutico
17.
Asian J Psychiatr ; 39: 165-168, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29636228

RESUMO

BACKGROUND: Bipolar Disorder (BD) is a chronic and disabling psychiatric illness with waxing and waning course. Lithium is the mainstay of treatment for Bipolar disorder (BD). There is limited literature on the clinical markers of Lithium treatment response from south Asia. METHODS: Two hundred and ten individuals with BD I and a history of at least 6 months of treatment with Lithium were recruited from the outpatient services of the National Institute of Mental Health and Neurosciences (NIMHANS) after obtaining informed consent. A diagnosis of BD I was made according to the DSM-IV criteria. The characterization of response to lithium prophylaxis was done using NIMH Retrospective Life Chart and "Retrospective Criteria of Long Term Treatment Response in Research Subjects with Bipolar Disorder" scale. RESULTS: There were 132 (62.86%) good responders and 78 (37.14%) non-responders. Good responders were noted to have less number of hospitalizations and more onset episode of depression than non-responders. Using continuous phenotype, Lithium response was inversely correlated with total number of episodes, number of episodes of mania/ depression, number of hospitalisations and presence of suicide attempt. Multivariate analysis only revealed number of episodes and hospitalization to be associated with Lithium response. CONCLUSION: Our Lithium response rates were higher than what have been reported in the few previous studies. Illness severity was the only factor associated with Lithium response. There is a need to examine this question in larger prospective samples and to focus on biological/ molecular markers of treatment response.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Adulto , Feminino , Humanos , Índia , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
18.
Eur J Drug Metab Pharmacokinet ; 44(3): 329-338, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30536114

RESUMO

BACKGROUND AND OBJECTIVE: Lithium, which is used to treat bipolar disorder, has a narrow therapeutic blood concentration range and quickly reaches clinically toxic levels. We performed a population pharmacokinetic analysis with a lithium tubular reabsorption model including urinary pH and investigated the relationship between blood lithium concentration and tremor as a side effect. METHODS: Routine clinical data, including 389 serum concentrations, were collected from 214 patients orally administered an adjusted amount of lithium carbonate. Pharmacokinetics were described using a one-compartment distribution model with first-order absorption and elimination. The fractions of the MID (Li+ + LiCO3-) and ION (2Li+ + CO32-) forms were calculated using the Henderson-Hasselbalch equation, and the influences of these fractions on clearance (CL) were evaluated. The rate of tremor development was analyzed using a logit model. RESULTS: Oral apparent CL (CL/F) was explained by nonrenal CL and renal CL, and renal CL was varied by the fractions of lithium forms influenced by urinary pH. The contribution of MID to CL was slightly larger than that of ION. The rate of tremor development was estimated to be more than 30% when the trough lithium concentration was greater than 1.26 mEq L-1. CONCLUSION: Renal function and urinary pH are important indices in lithium treatment, so the serum concentration of lithium may be predicted based on the renal function and urinary pH.


Assuntos
Antimaníacos/efeitos adversos , Antimaníacos/farmacocinética , Túbulos Renais/metabolismo , Carbonato de Lítio/efeitos adversos , Carbonato de Lítio/farmacocinética , Modelos Biológicos , Antimaníacos/uso terapêutico , Feminino , Meia-Vida , Humanos , Testes de Função Renal , Carbonato de Lítio/uso terapêutico , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Tremor/induzido quimicamente
19.
Fortschr Neurol Psychiatr ; 87(9): 483-491, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-30453335

RESUMO

For avoiding affective episodes, patients with bipolar disorders are treated with mood stabilizers. Under that term, the substances lithium, valproic acid, lamotrigine and carbamazepine are included. In the light of upcoming new psychiatric concepts, the use of second generation antipsychotics is also taken into consideration in pharmacological treatment. In this review, the relation between brain structure and the use of lithium in bipolar disorders is examined. Therefore, results from MRI-, DTI-, SPECT-studies assessing this relation, were included.Most of the studies are cross-sectional and examined the effects of lithium. The latter is associated with increased cortical and sub-cortical gray matter volume and ameliorative white matter microstructure. 7-lithium spectroscopy showed a significant difference in brain-lithium concentrations between remitted and non-remitted patients.There are preclinical studies reporting induction of promitotic and antiapoptotic effects by lithium. This literature underpins the hypothesis of lithium-induced neurogenesis. However, osmotic and physical effects of lithium could also explain the demonstrated volume gain in bipolar human brain.Cross-sectional design and small patient groups are typical limitations of numerous studies included in this review.Notably, with the 7-lithium spectroscopy of the central nervous system, new perspectives in clinical research to clarify pharmacokinetic differences between remitted and non-remitted bipolar patients can be established in future.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/patologia , Compostos de Lítio/uso terapêutico , Indução de Remissão , Antimaníacos/análise , Antimaníacos/química , Antimaníacos/uso terapêutico , Antipsicóticos/análise , Antipsicóticos/química , Antipsicóticos/uso terapêutico , Transtorno Bipolar/psicologia , Estudos Transversais , Humanos , Compostos de Lítio/análise , Compostos de Lítio/química
20.
Osteoporos Int ; 30(2): 257-266, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30374598

RESUMO

This systematic review and meta-analysis summarized the results from nine eligible observational studies. Lithium use was significantly associated with a decrease risk of fractures. INTRODUCTION: The association between lithium use and risk of fracture is uncertain. To date, there have been no meta-analyses that have studied the association between the two. We conducted a systematic review and meta-analysis to examine the effect of lithium medication on the risk of fracture. METHODS: A comprehensive literature search was performed in PubMed, Embase, and MEDLINE to include eligible observational studies. Three reviewers conducted the literature search, study selection, study appraisal, and data abstraction independently. Random effects models were used to obtain the overall estimate for meta-analysis. Cochran's Q and Higgins' I2 were used to assess heterogeneity. A funnel plot and Egger's regression test were employed to assess publication bias. RESULTS: Of the 3819 studies that were identified by our search strategy, eight were eligible for the systematic review, while seven of them qualified for the meta-analysis. In studies that reported risk ratio (RR) of fracture as an outcome (five studies [n = 1,134,722]), lithium use was associated with a 20% decrease in risk of fracture (RR = 0.80; 95% CI, 0.73-0.87; p < 0.01). A decreased risk of fracture associated with lithium was also observed in studies that adjusted for previous fractures (RR = 0.81; 95% CI, 0.73-0.89; p < 0.01). The decreased risk of fracture associated with lithium use remained consistent in all the analyses with different inclusion criteria. Neither significant heterogeneity nor significant publication bias was observed. CONCLUSION: The present systematic review and meta-analysis demonstrated that lithium use was associated with a significant decreased risk of fracture.


Assuntos
Antimaníacos/uso terapêutico , Compostos de Lítio/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Antimaníacos/farmacologia , Densidade Óssea/efeitos dos fármacos , Humanos , Compostos de Lítio/farmacologia , Estudos Observacionais como Assunto , Medição de Risco/métodos , Fatores de Risco
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