RESUMO
Evidence suggests that spironolactone, a nonselective mineralocorticoid receptor (MR) antagonist, modulates alcohol seeking and consumption. Therefore, spironolactone may represent a novel pharmacotherapy for alcohol use disorder (AUD). In this study, we tested the effects of spironolactone in a mouse model of alcohol drinking (drinking-in-the-dark) and in a rat model of alcohol dependence (vapor exposure). We also investigated the association between spironolactone receipt for at least 60 continuous days and change in self-reported alcohol consumption, using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), in a pharmacoepidemiologic cohort study in the largest integrated healthcare system in the US. Spironolactone dose-dependently reduced the intake of sweetened or unsweetened alcohol solutions in male and female mice. No effects of spironolactone were observed on drinking of a sweet solution without alcohol, food or water intake, motor coordination, alcohol-induced ataxia, or blood alcohol levels. Spironolactone dose-dependently reduced operant alcohol self-administration in dependent and nondependent male and female rats. In humans, a greater reduction in alcohol consumption was observed among those who received spironolactone, compared to propensity score-matched individuals who did not receive spironolactone. The largest effects were among those who reported hazardous/heavy episodic alcohol consumption at baseline (AUDIT-C ≥ 8) and those exposed to ≥ 50 mg/day of spironolactone. These convergent findings across rodent and human studies demonstrate that spironolactone reduces alcohol use and support the hypothesis that this medication may be further studied as a novel pharmacotherapy for AUD.
Assuntos
Alcoolismo , Humanos , Masculino , Feminino , Ratos , Animais , Camundongos , Alcoolismo/tratamento farmacológico , Espironolactona/uso terapêutico , Espironolactona/farmacologia , Roedores , Estudos de Coortes , Consumo de Bebidas Alcoólicas/tratamento farmacológico , EtanolRESUMO
OBJECTIVES: Recent research has focused on the inflammatory cascade as a key culprit in the etiology of bipolar disorder. We hypothesized that celecoxib, via its anti-inflammatory properties, may have a therapeutic role in mood disorder. METHODS: Forty-six inpatients with the diagnosis of acute bipolar mania without psychotic features participated in a parallel, randomized, double-blind, placebo-controlled trial, and underwent six weeks of treatment with either celecoxib (400 mg daily) or placebo as an adjunctive treatment to sodium valproate. Patients were evaluated using the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS). The primary outcome measure with respect to efficacy was the mean decrease in YMRS score from baseline to the study endpoint, which was compared between the two groups. RESULTS: A significant difference was observed in the change in YMRS scores on Day 42 compared to baseline in the two groups (p < 0.001). The changes at the endpoint compared to baseline were -29.78 ± 21.78 (mean ± standard deviation) and -21.78 ± 7.16 for the celecoxib and placebo groups, respectively. A significantly higher remission rate was observed in the celecoxib group (87.0%) than the placebo group (43.5%) at Week 6 (p = 0.005). General linear model repeated measures demonstrated a significant effect for the time × treatment interaction on the YMRS scores [F(2.27,99.98) = 6.67, p = 0.001]. CONCLUSIONS: Celecoxib is an effective adjuvant therapy in the treatment of manic episodes (without psychotic features) of bipolar mood disorder. The mood-stabilizing role of the drug might be mediated via its action on the inflammatory cascade.
Assuntos
Transtorno Bipolar , Celecoxib/administração & dosagem , Inflamação/tratamento farmacológico , Ácido Valproico/administração & dosagem , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Ácido Valproico/uso terapêuticoRESUMO
OBJECTIVES: According to the proposed interference of N-acetylcysteine (NAC) with pathophysiologic processes of autistic disorders (ADs), we aimed to assess the effectiveness and safety of NAC as an adjunct to risperidone in the treatment of ADs in a randomized, double-blind, clinical trial. METHODS: The participants were referred outpatients between 4 and 12 years of age with the diagnosis of ADs and a score of more than 12 on Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale score. The participants were randomized into 2 groups. One group received risperidone plus NAC, and the other group received risperidone plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and the dose of NAC was 600 to 900 mg/d. The main outcome was mean decrease in the ABC-C irritability subscale score from baseline at 5 and 10 weeks. Changes in other subscales were considered as secondary outcome measures. RESULTS: Forty patients completed the 10-week trial. Baseline characteristics including age, sex and body weight, as well as baseline scores in 5 subscales did not demonstrate statistically significant difference between the 2 groups. Repeated-measures analysis showed significant effect for time × treatment interaction in irritability (P = 0.01) and hyperactivity/noncompliance (P = 0.02) subscales. By week 10, the NAC group showed significantly more reduction in irritability (P = 0.02) and hyperactivity/noncompliance (P = 0.01) subscales scores. CONCLUSIONS: N-acetylcysteine can be considered as an adjuvant therapy for ADs with beneficial therapeutic outcomes.
Assuntos
Acetilcisteína/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Autístico/fisiopatologia , Sequestradores de Radicais Livres/uso terapêutico , Humor Irritável/efeitos dos fármacos , Risperidona/uso terapêutico , Transtorno Autístico/tratamento farmacológico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
OBJECTIVES: Limited pharmacological options are available for the management of Alzheimer's disease (AD) in severe stages. Cognitive-enhancing properties of saffron, the dried stigma of Crocus sativus L., have been evidenced in different studies. We aimed to compare the efficacy and safety of saffron extract versus memantine in reducing cognitive deterioration of patients with moderate to severe AD. METHODS: In this randomized double-blind parallel-group study, 68 patients with moderate to severe AD (Mini-Mental State Examination score of 8-14) received memantine (20 mg/day) or saffron extract (30 mg/day) capsules for 12 months. Participants were evaluated every month by Severe Cognitive Impairment Rating Scale (SCIRS) and Functional Assessment Staging (FAST) in addition to recording the probable adverse events. RESULTS: Both treatment groups showed similar outcomes as demonstrated by insignificant effect for time × treatment interaction on SCIRS scores [F(2.95, 194.78) = 2.25, p = 0.08]. There was no significant difference between the two groups in the scores changes from baseline to the endpoint on SCIRS (p = 0.38) and FAST (p = 0.87). The frequency of adverse events was not significantly different between the two groups as well. CONCLUSIONS: In addition to its favorable safety profile, 1-year administration of saffron extract capsules showed to be comparable with memantine in reducing cognitive decline in patients with moderate to severe AD. Confirmatory studies with larger sample sizes and longer follow-up periods are warranted.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Crocus , Memantina/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Humanos , Irã (Geográfico) , Masculino , Memantina/efeitos adversos , Fitoterapia/efeitos adversos , Extratos Vegetais/efeitos adversos , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
OBJECTIVE: A significant correlation exists between coronary artery diseases and depression. The aim of this trial was to compare the efficacy and safety of saffron versus fluoxetine in improving depressive symptoms of patients who were suffering from depression after performing percutaneous coronary intervention (PCI). METHODS: In this randomized double-blind parallel-group study, 40 patients with a diagnosis of mild to moderate depression who had undergone PCI in the last six months were randomized to receive either fluoexetine (40mg/day) or saffron (30mg/day) capsule for six weeks. Participants were evaluated by Hamilton depression rating scale (HDRS) at weeks 3 and 6 and the adverse events were systemically recorded. RESULTS: By the study endpoint, no significant difference was detected between two groups in reduction of HDRS scores (P=0.62). Remission and response rates were not significantly different as well (P=1.00 and P=0.67; respectively). There was no significant difference between two groups in the frequency of adverse events during this trial. LIMITATIONS: Relatively small sample size and short observational period were the major limitations of this study. CONCLUSION: Short-term therapy with saffron capsules showed the same antidepressant efficacy compared with fluoxetine in patients with a prior history of PCI who were suffering from depression.