Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials

The objective of this analysis was to determine if there are sex differences with esketamine for treatment-resistant depression (TRD). Post hoc analyses of three randomized, controlled studies of esketamine in patients with TRD (TRANSFORM-1, TRANSFORM-2 [18–64 years], TRANSFORM-3 [≥ 65 years]) were performed. In each 4-week study, adults with TRD were randomized to esketamine or placebo nasal spray, each with a newly initiated oral antidepressant. Change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed by sex in pooled data from TRANSFORM-1/TRANSFORM-2 and separately in data from TRANSFORM-3 using a mixed-effects model for repeated measures. Use of hormonal therapy was assessed in all women, and menopausal status was assessed in women in TRANSFORM-1/TRANSFORM-2. Altogether, 702 adults (464 women) received ≥ 1 dose of intranasal study drug and antidepressant. Mean MADRS total score (SD) decreased from baseline to day 28, more so among patients treated with esketamine/antidepressant vs. antidepressant/placebo in both women and men: TRANSFORM-1/TRANSFORM-2 women—esketamine/antidepressant -20.3 (13.19) vs. antidepressant/placebo -15.8 (14.67), men—esketamine/antidepressant -18.3 (14.08) vs. antidepressant/placebo -16.0 (14.30); TRANSFORM-3 women—esketamine/antidepressant -9.9 (13.34) vs. antidepressant/placebo -6.9 (9.65), men—esketamine/antidepressant -10.3 (11.96) vs. antidepressant/placebo -5.5 (7.64). There was no significant sex effect or treatment-by-sex interaction (p > 0.35). The most common adverse events in esketamine-treated patients were nausea, dissociation, dizziness, and vertigo, each reported at a rate higher in women than men. The analyses support antidepressant efficacy and overall safety of esketamine nasal spray are similar between women and men with TRD. The TRANSFORM studies are registered at clinicaltrials.gov (identifiers: NCT02417064 (first posted 15 April 2015; last updated 4 May 2020), NCT02418585 (first posted 16 April 2015; last updated 2 June 2020), and NCT02422186 (first posted 21 April 2015; last updated 29 September 2021)).

VALIDATED NOVEL SPECTROSCOPIC METHOD FOR ESTIMATION OF TRIAMCINOLONE ACETONIDE IN NASAL SPRAY

A simple, sensitive, accurate, precise and cost-effective pH independent spectrophotometric method has been developed for the estimation of triamcinolone acetonide in nasal sprays. Estimation was carried out at the isosbestic point of drug solutions, Isosbestic point was measured by scanning equimolar solution of triamcinolone acetonide separately in phosphate buffer pH 3.0, phosphate buffer pH 7.0 and phosphate buffer pH 10.0 at a concentration of 10 µg mL-1. They were scanned in the wavelength range of 200-400 nm. The isosbestic point was found to be 230.0 nm in acidic, basic and neutral condition; hence pH independent wavelength 230 nm was used for estimation of triamcinolone acetonide. The method observed linear response in the concentration range of 3-18 µg mL-1 at 230 nm. Developed method has been validated in accordance with ICH guideline Q2 R1 for several parameters like linearity, precision, accuracy, limit of detection and limit of quantification. The developed and validated analytical method was successfully applied to the estimation of triamcinolone acetonide in marketed nasal spray formulations.

Iota-Carrageenan Prevents the Replication of SARS-CoV-2 in a Human Respiratory Epithelium Cell Line in vitro

Iota-carrageenan is a sulfated polysaccharide extracted from red seaweeds, which, formulated into a nasal spray, has already been proven safe and effective in viral upper respiratory infections. In Calu-3, a human respiratory epithelium cell line, we explored the activity of a formula of iota-carrageenan and sodium chloride against SARS-CoV-2. In this study, the assayed formula, already approved as a nasal spray for human use, effectively inhibited SARS-CoV-2 infection, providing a more substantial reference for clinical studies or developments.

Budesonide Use in the Outpatient Department in a Public Hospital in Al-Kharj

Aim: This study aimed to describe the prescribing pattern of budesonide nebulizer and budesonide nasal spray in a public hospital in Alkharj. Methodology: This retrospective study was conducted in a public hospital in Alkharj city. The outpatient prescriptions were reviewed to describe the use of budesonide in the period between 01-01- 2018 and 31-06-2018. The study included budesonide forms that are delivered directly to the respiratory system, so budesonide nebulizer and budesonide nasal spray were included in the study and other dosage forms were excluded. Results: About 53.12% of the prescribed budesonide was in the form of nebulizer and 46.88% was in the form of nasal spray. Most of them were males (62.50%) and about 43.75% of them were less than 10 years. More than 53% of the prescriptions were written by residents and 40.62% were written by consultants. The most commonly prescribed department was pediatrics department (43.75%) followed by Ear-Nose-Throat (E.N.T) department (18.75%) and emergency (18.75%). Conclusion: The present study showed that the use of budesonide was uncommon in the outpatient setting. More studies are needed to explore the frequency of prescribing other dosage forms of budesonide and to explore the frequency of prescribing other alternative agents.

TIMolol nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia (HHT) – study protocol of the prospective, randomized, double-blind, controlled cross-over TIM-HHT trial

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an inherited orphan disease, in which the absence of capillary beds between arterioles and venules lead to arteriovenous shunts. Epistaxis is the core symptom. Several case reports have described the nonselective beta-adrenergic receptor antagonist timolol as a successful treatment method of nosebleeds due in HHT patients. OBJECTIVE: TIM-HHT is a single-site, prospective, randomized, placebo-controlled, double-blind, cross-over study to investigate whether the efficacy of standard laser treatment of epistaxis in HHT patients can be increased by the additional use of timolol nasal spray (1 mg/d). METHODS: Twenty patients will be randomly allocated to one of two treatment sequences. Primary outcome is the severity of epistaxis determined by the Epistaxis Severity Score (ESS). Secondary outcomes are subjective satisfaction, quality of life, as well as the hemoglobin, ferritin, and transferrin levels of the participating patients. Safety outcome is assessed by means of pulse, blood pressure, and adverse events. CONCLUSION: TIM-HHT will evaluate the efficacy and safety of timolol as an additional treatment of epistaxis in HHT patients in a three-month trial period. Benzalkonium chloride is used as a placebo, which has no documented positive effect on the nasal mucosa and hence on epistaxis in HHT patients (in contrast to saline). TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00020994. Registered on 10 March 2020