Effects of sex and hydration status on kappa opioid receptor-mediated diuresis in rats.

Understanding the function of the kappa opioid receptor (KOP) is crucial for the development of novel therapeutic interventions that target KOP for the treatment of pain, stress-related disorders and other indications. Activation of KOP produces diuretic effects in rodents and man. Sex is a vital factor to consider when assessing drug response in pre-clinical and clinical studies. In this study, the diuretic effect of the KOP agonist, U50488 (1-10 mg/kg), was investigated in both adult female and male Wistar rats that were either normally hydrated or water-loaded. The KOP antagonist norbinaltorphimine (norBNI, 10 mg/kg) was administered 24 h prior to U50488 to confirm the involvement of KOP. U50488 elicited a significant diuretic response at doses ≥ 3 mg/kg in both female and male rats independent of hydration status. U50488 diuretic effects were inhibited by norBNI pre-administration. Water-loading reduced data variability for urine volume in males, but not in females, compared with normally hydrated rats. Sex differences were also evident in U50488 eliciting a significant increase in sodium and potassium ion excretion only in males. This may suggest different mechanisms of U50488 diuretic action in males where renal excretion mechanisms are directly affected more than in females.

An analysis of antidepressant prescribing trends in England 2015-2019.

Background Growing concerns about the impact of coronavirus disease 2019 (COVID-19) will likely lead to increased mental health diagnoses and treatment. To provide a pre-COVID-19 baseline, we have examined antidepressant prescribing trends for 5 years preceding COVID-19. Methods A retrospective analysis of anonymised data on medicines prescribed by GPs in England from the Open-Prescribing Database (January 2015 to December 2019) identified the 10 most prescribed antidepressant and, for comparison, cardiovascular medicines. Results Prescription items for the 10 most prescribed antidepressants rose 25% from 58 million (2015) to 72 million (2019). Citalopram was the most prescribed antidepressant; prescriptions for sertraline rose fastest at 2 million items year on year. Over the same period, costs for antidepressant prescribing fell 27.8%. Across all Clinical Commissioning Groups (CCGs) in England, antidepressant prescribing levels, adjusted for population were positively correlated with the index of multiple deprivation (IMD) score. In comparison, prescribing for the top 10 most prescribed cardiovascular medicines increased by 2.75% from 207 million (2015) to 213 million (2019) items. Limitations Anonymised data in the Open-Prescribing Database means no patient diagnoses or treatment plans are linked to this data. Conclusion Antidepressant prescribing, particularly sertraline, is increasing. Prescribing is higher in more deprived regions, but costs are falling to < 2% of all items prescribed. Absolute numbers of prescriptions for cardiovascular medicines are higher, likely reflecting the greater prevalence of cardiovascular disease, and are rising more slowly. This study will enable future work to look at the impact of COVID-19 on prescribing for mental health.