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Bipolar disorder (BD) is a chronic and refractory disease with high probability of morbidity and mortality. Although epidemiological studies have established a strong association between BD and immune dysfunction, the precise etiology is still debatable, and the underpinning mechanism remains poorly investigated and understood. In the present study, manic-like symptoms of BD were induced in rats after intracerebroventricular administration of ouabain. Aspirin, a commonly used anti-inflammatory agent, was used to treat the induced manic-like symptoms and inflammation. Concentrations of a spectrum of inflammatory cytokines were examined by enzyme-linked immunosorbent assay in both plasma and brain tissues, and expression of Toll-like receptors 3 and 4 were determined in rat brains. Locomotor activity was monitored with open-field test to assess the effects of ouabain challenge and to evaluate the treatment efficacy of aspirin. Ouabain administration recapitulated many mania-like features such as increased stereotypic counts, traveling distance in open-field test, and decreased expression of brain-derived neurotrophic factor, interferon gamma, and Toll-like receptor 3, which were frequently found in patients with BD. These abnormalities could be partially reversed by aspirin. Our findings suggest that aspirin could be used as a promising adjunctive therapy for BD.
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Background: The relation between the ATP-binding cassette subfamily B member 1 (ABCB1) gene and major depressive disorder (MDD) has been studied in a local Chinese Han population. MDD is associated with the rs2032582 (G2677T) and rs1128503 (C1236T) single-nucleotide polymorphisms (SNPs) of ABCB1 but not with rs1045642, rs2032583, rs2235040, and rs2235015. This study aims to explore the potential correlations of therapeutic responses with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in a local Chinese Han population. Methods: The study population included 292 patients with MDD. All patients were assessed at baseline and at first, second, fourth, and sixth weeks according to the 17-item Hamilton Rating Scale for Depression (HAM-D17) to determine their therapeutic responses to SSRIs and SNRIs. Results: In the SSRI therapy group, the genotype or allele distribution of six SNPs was not significantly different between responders and nonresponders. In the SNRI therapy group, only rs2032583 was associated with a therapeutic response to SNRIs. The C allele of the ABCB1 rs2032583 polymorphism was negatively correlated with therapeutic responses according to logistic regression analysis. Conclusion: The ABCB1 gene polymorphisms may not be associated with therapeutic responses to SSRIs but not with SNRIs. The TT genotype of rs2032583 could be a predictive factor of improved treatment responses to SNRIs in the Chinese population. These findings should be replicated in future studies with larger patient groups.
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BACKGROUND: Human P-glycoprotein encoded by the ATP-binding cassette sub-family B member 1 (ABCB1) gene is expressed in the blood-brain barrier. ABCB1 protects the brain from many drugs and toxins such as glucocorticoids through the efflux pump. Recent evidence suggests that a specific allele of the ABCB1 gene confers susceptibility to major depressive disorder (MDD) in the Japanese population. The aim of this study was to explore the association of ABCB1 gene polymorphisms with MDD in a local Chinese Han population. METHODS: Two hundred and ninety-two MDD patients and 208 unrelated individuals were matched by age and sex and examined using a case-control design. Six single nucleotide polymorphisms (SNPs) of the ABCB1 gene, including rs1045642, rs2032583, rs2032582, rs2235040, rs1128503, and rs2235015, were genotyped by ligase detection reaction and multiplex polymerase chain reaction. Linkage disequilibrium and haplotype analysis were investigated in the two study groups. RESULTS: Significant protection for MDD individuals carrying the TG haplotype of rs1045642-rs2032582 was observed (odds ratio 0.470, 95% confidence interval 0.251-0.897, P=0.01). The rs2032582 (G2677T) and rs1128503 (C1236T) SNPs of ABCB1 showed nominal associations with MDD; the other four SNPs of the ABCB1 gene were not associated with MDD. CONCLUSION: Chinese individuals carrying the TG haplotype of rs1045642-rs2032582 had a nearly 53% lower risk of developing MDD. To the best of our knowledge, this is the first report to analyze the effect of ABCB1 polymorphism on the risk of MDD in a Chinese population.
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OBJECTIVE: To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS: In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for 6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of the study. The secondary efficacy measurements were the response and remission rates, the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end of the study, and the change of the HAMD-14 total score and quality of sleep [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study period. RESULTS: The mean maximum daily dose was 273.11 mg for the trazodone group and 290.92 mg for the placebo group. At the end of the study, there was a significant difference between the two groups in the HAMD-17 change score (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages at 1 week of treatment, and the effect lasted until the end of the study (week 6). The response and remission rates of the trazodone group were significantly higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001; remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions of trazodone were mild to moderate, and the most frequent adverse reactions (≥5%) were dizziness, dry mouth, somnolence, and nausea. CONCLUSIONS: Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated.
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Antidepresivos de Segunda Generación/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trazodona/uso terapéutico , Adulto , Antidepresivos de Segunda Generación/administración & dosificación , Antidepresivos de Segunda Generación/efectos adversos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trazodona/administración & dosificación , Trazodona/efectos adversos , Resultado del TratamientoRESUMEN
This randomized, parallel-group, open study investigated the efficacy and safety of risperidone oral solution (RIS-OS) in combination with clonazepam and intramuscular haloperidol for the treatment of acute agitation in patients with schizophrenia, and the study explored the possibility of decreasing the efficacy of an acute 6-week treatment by switching intramuscular haloperidol injection to RIS-OS. Two hundred and five agitation-exhibiting schizophrenic inpatients at six hospitals were originally included in the study. The 47-day trial consisted of 5 days (session I) of receiving either oral treatment (RIS-OS plus clonazepam) or intramuscular treatment (intramuscular haloperidol) and a 42-day (session II) period of either withdrawing from clonazepam or shifting from intramuscular haloperidol to a RIS-OS period. The primary efficacy outcome was measured as the change in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) in session I and the change in the PANSS in session II. Safety was assessed by the frequency of the adverse events. Mean PANSS-EC improvement was significant after 5 days of treatment in both groups (P>0.05) and was similar between the two treatment groups (P<0.01). Most patients' PANSS-EC scores improved or remained stable during the drawback/shift treatment period. Efficacy was not significantly different between the two treatment groups after the 6-week treatment (P>0.05). However, combination treatment exhibited greater efficacy, and adverse events, especially extrapyramidal symptoms, were lower with the oral treatment than with the intramuscular treatment in session I. These results show that RIS-OS in combination with clonazepam is an effective treatment, comparable with intramuscular haloperidol, and is well-tolerated for acute agitation in patients with schizophrenia.
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Antipsicóticos/uso terapéutico , Haloperidol/efectos adversos , Agitación Psicomotora/tratamiento farmacológico , Risperidona/uso terapéutico , Esquizofrenia/fisiopatología , Administración Oral , Adulto , Acatisia Inducida por Medicamentos/prevención & control , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , China , Clonazepam/administración & dosificación , Clonazepam/efectos adversos , Clonazepam/uso terapéutico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Monitoreo de Drogas , Quimioterapia Combinada/efectos adversos , Femenino , Haloperidol/administración & dosificación , Haloperidol/uso terapéutico , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/uso terapéutico , Inyecciones Intramusculares , Masculino , Agitación Psicomotora/etiología , Agitación Psicomotora/fisiopatología , Risperidona/administración & dosificación , Risperidona/efectos adversos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
RATIONALE: S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD). OBJECTIVE: The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients. METHODS: In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10-20 mg/d) or citalopram (20-40 mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator. RESULTS: Two hundred and three (85%) patients completed the trial. The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study. CONCLUSIONS: The study suggests that escitalopram 10-20 mg/d are as effective and safe as citalopram 20-40 mg/d in the short-term treatment for Chinese MDD patients.
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Antidepresivos de Segunda Generación/uso terapéutico , Citalopram/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Adulto , Antidepresivos de Segunda Generación/administración & dosificación , Antidepresivos de Segunda Generación/efectos adversos , Pueblo Asiatico , China , Citalopram/administración & dosificación , Citalopram/efectos adversos , Trastorno Depresivo Mayor/fisiopatología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Inducción de Remisión , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to assess the efficacy of metformin in preventing olanzapine-induced weight gain. METHOD: Forty patients with schizophrenia were randomly assigned to treatment for 12 weeks with olanzapine, 15 mg/day, plus metformin, 750 mg/day (N=20), or olanzapine, 15 mg/day, plus placebo (N=20). This investigation was conducted in a double-blind fashion. Planned assessments included body weight, body mass index, proportion of patients who gained more than 7% of their baseline weight at the end of the 12-week treatment, waist circumference, waist-to-hip ratio, fasting glucose and insulin, insulin resistance index, and scores on the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). RESULTS: Of the 40 patients who were randomly assigned, 37 (92.5%) completed treatments. The weight, body mass index, waist circumference, and waist-to-hip ratio levels increased less in the olanzapine plus metformin group relative to the olanzapine plus placebo group during the 12-week follow-up period. The insulin and insulin resistance index values of the olanzapine plus placebo group increased significantly at weeks 8 and 12. In contrast, the insulin and insulin resistance index levels of the olanzapine plus metformin group remained unchanged. Significantly fewer patients in the olanzapine plus metformin group relative to patients in the olanzapine plus placebo group increased their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight gain. There was a significant decrease in SAPS and SANS scores within each group from baseline to week 12, with no between-group differences. Metformin was tolerated well by all patients. CONCLUSIONS: Metformin was effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drug-naive first-episode schizophrenia patients. Patients displayed good adherence to this type of preventive intervention.
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Antipsicóticos/efectos adversos , Benzodiazepinas/efectos adversos , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Obesidad/prevención & control , Esquizofrenia/tratamiento farmacológico , Aumento de Peso/efectos de los fármacos , Adolescente , Adulto , Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Índice de Masa Corporal , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Estudios de Seguimiento , Humanos , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Persona de Mediana Edad , Obesidad/inducido químicamente , Olanzapina , Placebos , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Esquizofrenia/diagnóstico , Resultado del Tratamiento , Relación Cintura-CaderaRESUMEN
CONTEXT: Weight gain, a common adverse effect of antipsychotic medications, is associated with medical comorbidities in psychiatric patients. OBJECTIVE: To test the efficacy of lifestyle intervention and metformin alone and in combination for antipsychotic-induced weight gain and abnormalities in insulin sensitivity. DESIGN, SETTING, AND PATIENTS: A randomized controlled trial (October 2004-December 2006) involving 128 adult patients with schizophrenia in the Mental Health Institute of the Second Xiangya Hospital, Central South University, China. Participants who gained more than 10% of their predrug weight were assigned to 1 of 4 treatment groups. INTERVENTIONS: Patients continued their antipsychotic medication and were randomly assigned to 12 weeks of placebo, 750 mg/d of metformin alone, 750 mg/d of metformin and lifestyle intervention, or lifestyle intervention only. MAIN OUTCOME MEASURES: Body mass index, waist circumference, insulin levels, and insulin resistance index. RESULTS: All 128 first-episode schizophrenia patients maintained relatively stable psychiatric improvement. The lifestyle-plus-metformin group had mean decreases in body mass index (BMI) of 1.8 (95% confidence interval [CI], 1.3-2.3), insulin resistance index of 3.6 (95% CI, 2.7-4.5), and waist circumference of 2.0 cm (95% CI, 1.5-2.4 cm). The metformin-alone group had mean decreases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 3.5 (95% CI, 2.7-4.4), and waist circumference of 1.3 cm (95% CI, 1.1-1.5 cm). The lifestyle-plus-placebo group had mean decreases in BMI of 0.5 (95% CI, 0.3-0.8) and insulin resistance index of 1.0 (95% CI, 0.5-1.5). However, the placebo group had mean increases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 0.4 (95% CI, 0.1-0.7), and waist circumference of 2.2 cm (95% CI, 1.7-2.8 cm). The lifestyle-plus-metformin treatment was significantly superior to metformin alone and to lifestyle plus placebo for weight, BMI, and waist circumference reduction. CONCLUSIONS: Lifestyle intervention and metformin alone and in combination demonstrated efficacy for antipsychotic-induced weight gain. Lifestyle intervention plus metformin showed the best effect on weight loss. Metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone. Trial Registration clinicaltrials.gov Identifier: NCT00451399.