Reboxetine 4mg tablets

Post-stroke depression (PSD) is a common neuropsychiatric complication that adversely affects rehabilitation outcomes, cognitive recovery, and quality of life in stroke survivors. While selective serotonin reuptake inhibitors (SSRIs) are widely used as first-line treatment, serotonin-norepinephrine reuptake inhibitors (SNRIs) have emerged as potential alternatives with broader neurochemical targets. This systematic review aimed to compare the efficacy of SSRIs and SNRIs in the treatment and prevention of PSD. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Google Scholar in accordance with PRISMA guidelines, applying filters for English-language clinical trials. Five randomized controlled trials met the inclusion criteria and were analyzed. The findings revealed that both SSRIs and SNRIs significantly improved depressive symptoms, with escitalopram showing early and superior antidepressant effects compared to sertraline. SNRIs like duloxetine and reboxetine demonstrated added benefits in cognitive outcomes, prevention of PSD, and symptom subtype-specific efficacy, particularly in retarded depression. While the overall risk of bias was low in most studies, limitations such as small sample sizes and limited direct head-to-head comparisons were noted. These results support the clinical utility of both drug classes and emphasize the need for individualized pharmacologic strategies based on patient characteristics and symptom profiles.

Abstract licence: CC BY

AIM: Whether histamine H3 receptor antagonists (H3R-ANTs)/inverse agonists (H3R-IAs) provides benefit for the treatment of schizophrenia remains unclear. This meta-analysis was conducted to address the above clinical question. METHODS: Cognitive Function Scale's composite score (primary), seven domains of cognitive function (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, and social cognition) score, University of California San Diego Performance-Based Skills Assessment score, psychopathology scales score, discontinuation rate, and incidence of individual adverse events were among the study outcomes. The standardized mean differences (SMD) or risk ratios (RR) with 95% confidence intervals (CIs) were calculated. RESULTS: Our meta-analysis included 11 double-blind, randomized, placebo-controlled trials (n = 754). Our study evaluated ABT-288, betahistine, betahistine+reboxetine, GSK239512, MK-0249, and pitolisant. Betahistine has an H1-receptor agonistic reaction and H3-receptor antagonistic reaction, while other drugs only have an H3-receptor antagonistic/inverse agonistic reaction. Hence, we conducted a meta-analysis for all outcomes divided by betahistine or other pooled H3R-ANTs/H3R-IAs. The study results show that betahistine outperformed placebo in the improvement of overall cognitive symptoms (SMD [95% CI] = -0.61 [-1.03, -0.18]), speed of processing (-0.44 [-0.87, -0.02]), attention/vigilance (-0.43 [-0.85, -0.01]), working memory (-0.48 [-0.90, -0.06]), verbal learning (-0.62 [-1.04, -0.19]), visual learning (-0.57 [-1.00, -0.15]), and betahistine+reboxetine was superior in the improvement of depressive symptoms (-4.04 [-5.10, -2.97]). Pitolisant outperformed placebo in depressive symptom improvement (-3.24 [-4.22, -2.26]). However, the results were derived from one betahistine, betahistine+reboxetine, or pitolisant study. Other pooled H3R-ANTs/H3R-IAs revealed risk of insomnia (RR [95% CI] = 2.18 [1.05, 4.55]). However, no differences were observed in other any outcomes between betahistine or other pooled H3R-ANTs/H3R-IAs and placebo. CONCLUSIONS: Some H3R-ANTs/H3R-IAs might provide benefit for the treatment of cognitive symptoms and depressive symptoms in individuals afflicted with schizophrenia.

Abstract licence: CC BY

BACKGROUND: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. RESEARCH QUESTION: Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? STUDY DESIGN AND METHODS: A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. RESULTS: completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P < .001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P < .001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P < .001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. INTERPRETATION: The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04449133; URL: www.clinicaltrials.gov.

Abstract licence: CC BY

Establishing regulatory limits for Drug Substance-Related Impurities (NDSRIs) is challenging due to the limited genotoxicity and carcinogenicity data available for many of these impurities, often leading to conservative approaches. In this study, we evaluated the genotoxic potential of two structurally related nitrosamines: N-nitrosomorpholine (NMOR) and N-nitroso reboxetine. Compared to the well-studied NMOR, there is little toxicological information available for N-nitroso reboxetine. Currently, both compounds have an acceptable intake value of 127 ng/day, based on a read-across using the available carcinogenicity data of NMOR. While both compounds tested positive in a series of in vitro and in vivo assays, we found that the mutagenic potential of N-nitroso reboxetine was significantly lower than that of NMOR. The benchmark dose (BMD) analysis of in vivo mutagenicity data supports an acceptable intake of 24,000 ng/day for N-nitroso reboxetine. Computational studies, carried out using the quantum-mechanical CADRE program, were consistent with in vitro and in vivo outcomes, suggesting an acceptable intake at or above 1500 ng/day for N-nitroso reboxetine. In comparison to NMOR, this prediction is supported by lower computed reactivity in the hydroxylation step, greater steric hindrance of the alpha carbons, and more facile proton transfer in the heterolysis toward the aldehyde metabolite. The data presented in this work can be used to refine and improve the Carcinogenic Potency Categorization Approach (CPCA). It also underscores the importance of collaboration between regulatory authorities, the pharmaceutical industry, and scientific researchers to address potential risks while avoiding overestimation of the acceptable intake limits for certain NDSRIs.

Abstract licence: CC BY-NC-ND

Reboxetine (REB) and sertraline (SER) are antidepressants. The antifungal potential of these drugs against planktonic Candida has been recently reported with limited data about their effects on Candidal biofilms. Biofilms are self-derived extracellular matrixes produced by the microbial population that is attached to biotic surfaces, such as vaginal and oral mucosa, or abiotic surfaces, such as biomedical devices, resulting in persistent fungal infections. The commonly prescribed antifungals, azoles, are usually less effective when biofilms are formed, and most of the prescribed antifungals are only fungistatic. Therefore, the current study investigates the antifungal potentials of REB and SER, alone and in combination with fluconazole (FLC) and itraconazole (ITR) against Candidal biofilms. Using proper controls, Candida species (Candida albicans, C. albicans; Candida krusei, C. krusei; and Candida glabrata, C. glabrata) were used to form biofilms in 96-well microplates. Serial dilutions corresponding to concentrations ranging from 2 to 4096 µg/mL of the target drugs (REB, SER, FLC, ITR) were prepared and added to the plates. Impairment of the biofilm biomass and biofilm metabolic viability was detected using the crystal violet (CV) assay and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. In the checkerboard assay, the sessile fractional inhibitory concentration index (SFICI) was calculated to evaluate the effects of drug combinations. SER was more effective in reducing the biomass than REB for C. albicans and C. glabrata, but both were equal for C. krusei. For the reduction in metabolic activity in C. albicans and C. glabrata, SER had a slight advantage over REB. In C. krusei, REB was slightly more potent. Overall, FLC and ITR were almost equal and produced more significant reductions in metabolic activity when compared to SER and REB, except for C. glabrata, where SER was almost equal to FLC. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of C. albicans. Synergism was detected between REB + ITR against biofilm cells of C. krusei. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of C. albicans, C. krusei, and C. glabrata. The results of the present study support the potential of SER and REB as anti-Candidal biofilm agents that are beneficial as a new antifungal to combat Candidal resistance.

Abstract licence: CC BY