RESUMO
INTRODUCTION: Despite possible risks of mania switching with the long-term use of antidepressants in patients with bipolar disorder (BD), these drugs may help in depressive episodes. Alterations in neurotrophic factor levels seem to be involved in the pathophysiology of BD. The present study aimed to evaluate the effect of acute treatment of imipramine on behavior and neurotrophic levels in rats submitted to the animal model for BD induced by ouabain. METHODS: Wistar rats received a single intracerebroventricular (ICV) injection of artificial cerebrospinal fluid or ouabain (10-3 M). Following the ICV administration, the rats were treated for 14 days with saline (NaCl 0.9%, i.p.), lithium (47.5 mg/kg, i.p.), or valproate (200 mg/kg, i.p.). On the 13th and 14th days of treatment, the animals received an additional injection of saline or imipramine (10 mg/kg, i.p.). Behavior tests were evaluated 7 and 14 days after ICV injection. Adrenal gland weight and concentrations of ACTH were evaluated. Levels of neurotrophins BDNF, NGF, NT-3, and GDNF were measured in the frontal cortex and hippocampus by ELISA test. RESULTS: The administration of ouabain induced mania- and depressive-like behavior in the animals 7 and 14 days after ICV, respectively. The treatment with lithium and valproate reversed the mania-like behavior. All treatments were able to reverse most of the depressive-like behaviors induced by ouabain. Moreover, ouabain increased HPA-axis parameters in serum and decreased the neurotrophin levels in the frontal cortex and hippocampus. All treatments, except imipramine, reversed these alterations. CONCLUSION: It can be suggested that acute administration of imipramine alone can be effective on depressive-like symptoms but not on neurotrophic factor alterations present in BD.
Assuntos
Transtorno Bipolar , Animais , Ratos , Antimaníacos/farmacologia , Antimaníacos/uso terapêutico , Transtorno Bipolar/induzido quimicamente , Fator Neurotrófico Derivado do Encéfalo/uso terapêutico , Modelos Animais de Doenças , Imipramina/farmacologia , Imipramina/uso terapêutico , Lítio/farmacologia , Lítio/uso terapêutico , Mania , Fatores de Crescimento Neural , Ouabaína/farmacologia , Ouabaína/uso terapêutico , Ratos Wistar , Ácido ValproicoRESUMO
Children are more prone to adverse effects of selective serotonin reuptake inhibitors than adults. The aim of this study is to review the bibliography on mania and hypomania induced by these antidepressants. Most of the young people diagnosed with bipolar disorder had been exposed to this type of drug. The hypomania associated with these antidepressants in children with anxiety disorders is as relevant as that of those who had previously received a diagnosis of depression. As a limitation, in the selected papers, the activation syndrome could or could not include (hypo) mania. When indicating an antidepressant, we must be extremely prudent and place special emphasis on the risk-benefit analysis. It is essential to conduct a thorough search of family history of bipolar disorder together with a personal history investigation and a meticulous analysis of the semiology of our patients due to the risks of (hypo) mania.
Assuntos
Transtorno Bipolar , Mania , Adolescente , Adulto , Antidepressivos/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Criança , Humanos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêuticoRESUMO
In rats, lisdexamfetamine (LDX) induces manic-like behaviors such as hyperlocomotion and increases in appetitive 50-kHz ultrasonic vocalizations (USV), which are prevented by antimanic drugs, such as lithium. Inhibition of glycogen synthase kinase 3 beta (GSK3ß) and antioxidant activity have been associated with antimanic effects. Thus, the aim of the present study was to evaluate the possible antimanic-like effects of andrographolide (ANDRO), a GSK3ß inhibitor, on LDX-induced hyperlocomotion and 50-kHz USV increases. In addition, the effect of ANDRO was studied on LDX-induced oxidative stress. Lithium was used as positive control. Adult Wistar rats were treated with vehicle, lithium (100 mg/kg i.p., daily) or ANDRO (2 mg/kg i.p., 3 times a week) for 21 days. On the test day, either 10 mg/kg LDX or saline was administered i.p. and USV and locomotor activity were recorded. LDX administration increased the number of 50-kHz calls, as well as locomotor activity. Repeated treatment with lithium or ANDRO prevented these effects of LDX on 50-kHz USV and locomotor activity. LDX increased lipid peroxidation (LPO) levels in rat striatum and both lithium and ANDRO prevented this effect. LPO levels in rat striatum were positively correlated with increases in 50-kHz USV emission as well as hyperlocomotion. In conclusion, the present results indicate that ANDRO has antimanic-like effects, which may be mediated by its antioxidant properties.
Assuntos
Transtorno Bipolar , Ultrassom , Animais , Antimaníacos/farmacologia , Antimaníacos/uso terapêutico , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Modelos Animais de Doenças , Diterpenos , Mania , Estresse Oxidativo , Ratos , Ratos Wistar , Vocalização AnimalRESUMO
This paper discusses essential issues related to long-term lithium therapy and presents a case of successful 50-year lithium treatment. Lithium is currently regarded as the drug of choice for preventing manic and depressive recurrences in bipolar disorder. In 1/3 of patients with bipolar disorder, long-term monotherapy with lithium can completely prevent recurrences of abnormal mood. Numerous clinical and psychosocial factors associated with a good response to lithium have been described. Lithium is more efficacious than other mood stabilizers, and its long-term treatment significantly exceeds them. Lithium also exerts antisuicidal, immunomodulatory, and neuroprotective effects. The main problems associated with long-term lithium treatment include kidney, thyroid, and probably cognitive issues. In this paper, a case of successful continuous lithium treatment for 50 years in a 79-year-old female patient is presented. In this patient, apart from maintaining a euthymic state, long-term lithium treatment also exerted a favorable effect on general health, especially the elimination of viral and other respiratory infections. It is concluded that ultra-long term lithium therapy can enable good professional and psychosocial functioning for many patients, and the possible somatic side effects are manageable.
Assuntos
Transtorno Bipolar , Lítio , Anticonvulsivantes/uso terapêutico , Antimaníacos/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Feminino , Humanos , Lítio/uso terapêutico , Compostos de Lítio/efeitos adversosRESUMO
Objectives: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. Methods: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). Results: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. Conclusions: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.
Assuntos
Humanos , Criança , Adolescente , Adulto , Adulto Jovem , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior , Pais , Estudos Prospectivos , Manual Diagnóstico e Estatístico de Transtornos MentaisRESUMO
OBJECTIVES: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. METHODS: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). RESULTS: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. CONCLUSIONS: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Adulto , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Pais , Estudos Prospectivos , Adulto JovemRESUMO
Metabolic and psychiatric disorders present a bidirectional relationship. GLP-1 system, known for its insulinotropic effects, has also been associated with numerous regulatory effects in cognitive and emotional processing. GLP-1 receptors (GLP-1R) agonists present neuroprotective and antidepressant/anxiolytic properties. However, the effects of GLP-1R agonism in bipolar disorder (BD) mania and the related cognitive disturbances remains unknown. Here, we investigated the effects of the GLP-1R agonist liraglutide (LIRA) at monotherapy or combined with lithium (Li) against D-amphetamine (AMPH)-induced mania-like symptoms, brain oxidative and BDNF alterations in mice. Swiss mice received AMPH 2 mg/kg or saline for 14 days. Between days 8-14, they received LIRA 120 or 240 µg/kg, Li 47.5 mg/kg or the combination Li + LIRA, on both doses. After behavioral evaluation the brain areas prefrontal cortex (PFC), hippocampus and amygdala were collected. AMPH induced hyperlocomotion, risk-taking behavior and multiple cognitive deficits which resemble mania. LIRA reversed AMPH-induced hyperlocomotion, working and recognition memory impairments, while Li + LIRA240 rescued all behavioral changes induced by AMPH. LIRA reversed AMPH-induced hippocampal oxidative and neurotrophic changes. Li + LIRA240 augmented Li antioxidant effects and greatly reversed AMPH-induced BDNF changes in PFC and hippocampus. LIRA rescued the weight gain induced by Li in the course of mania model. Therefore, LIRA can reverse some mania-like behavioral alterations and combined with Li augmented the mood stabilizing and neuroprotective properties of Li. This study points to LIRA as a promising adjunctive tool for BD treatment and provides the first rationale for the design of clinical trials investigating its possible antimanic effect.
Assuntos
Transtorno Bipolar/tratamento farmacológico , Dextroanfetamina/toxicidade , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Liraglutida/administração & dosagem , Lítio/administração & dosagem , Mania/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Animais , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/psicologia , Sinergismo Farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Mania/induzido quimicamente , Mania/psicologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/psicologia , CamundongosRESUMO
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.