Safety and tolerability of edivoxetine as adjunctive treatment to selective serotonin reuptake inhibitor antidepressants for patients with major depressive disorder

Objective: The aim of this analysis was to assess the safety profile of edivoxetine as adjunctive treatment to selective serotonin reuptake inhibitor (SSRI) antidepressants. Methods: A pooled analysis was conducted on data obtained from the integrated safety database of edivoxetine as adjunctive treatment to SSRIs. Safety and tolerability assessments included discontinuation rates, spontaneously reported treatment-emergent adverse events (TEAEs), clinical laboratory tests, blood pressure (BP) and pulse, and electrocardiograms (ECGs). Results: The analysis included 1260 patients treated with adjunctive edivoxetine and 806 treated with adjunctive placebo. Study completion rates were 85.2% and 84.5% (p=0.994), respectively. Discontinuations due to adverse events were 4.9% and 3.5% (p=0.07), respectively. Significantly more patients in the adjunctive edivoxetine group compared with adjunctive placebo group reported at least one TEAE (56.8 vs 43.7%, p<0.001). The most common TEAEs (occurred ≥5% frequency) were hyperhidrosis, nausea, and tachycardia. Mean changes in sitting BP and pulse at the last visit were increased significantly in patients treated with adjunctive edivoxetine compared with adjunctive placebo (SBP: 2.7 vs 0.5 mm Hg, p<0.001; DBP: 4.1 vs 0.8 mm Hg, p<0.001; pulse: 8.8 vs –1.3 bpm, p<0.001). There were no clinically significant changes in laboratory measures. Conclusions: The tolerability and safety profile of edivoxetine as adjunctive treatment to SSRI antidepressants was consistent with its norepinephrine reuptake inhibitor mechanism of action, and was comparable with edivoxetine monotherapy treatment in patients with major depressive disorder

Challenges and complexities in designing cluster headache prevention clinical trials:A narrative review

OBJECTIVE: To provide a review of challenges in clinical trials for the preventive treatment of cluster headache (CH) and highlight considerations for future studies. BACKGROUND: Current guidelines for preventive treatment of CH are largely based on off‐label therapies supported by a limited number of small randomized controlled trials. Guidelines for clinical trial design for CH treatments from the International Headache Society were last issued in 1995. METHODS/RESULTS: Randomized controlled clinical trials were identified in the European and/or United States clinical trial registries with a search term of “cluster headache,” and manually reviewed. Cumulatively, there were 27 unique placebo‐controlled prevention trials for episodic and/or chronic CH, of which 12 were either ongoing, not yet recruiting, or the status was unknown. Of the remaining 15 trials, 5 were terminated early and 7 of the 10 completed trials enrolled fewer patients than planned or did not report the planned sample size. A systematic search of PubMed was also utilized to identify published manuscripts reporting results from placebo‐controlled preventive trials of CH. This search yielded 16 publications, of which 7 were registered. Through critical review of trial data and published manuscripts, challenges and complexities encountered in clinical trials for the preventive treatment of CH were identified. For example, the excruciating pain associated with CH demands a suitably limited baseline duration, rapid treatment efficacy onset, and poses a specific issue regarding duration of investigational treatment period and length of exposure to placebo. In episodic CH, spontaneous remission as part of natural history, and the unpredictability and irregularity of cluster periods across patients present additional key challenges. CONCLUSIONS: Optimal CH trial design should balance sound methodology to demonstrate efficacy of a potential treatment with patient needs and the natural history of the disease, including unique outcome measures and endpoint timings for chronic versus episodic CH

Stress and human health in diabetes: A report from the 19^th Chicago Biomedical Consortium symposium

Stress and diabetes coexist in a vicious cycle. Different types of stress lead to diabetes, while diabetes itself is a major life stressor. This was the focus of the Chicago Biomedical Consortium’s 19th annual symposium, “Stress and Human Health: Diabetes,” in November 2022. There, researchers primarily from the Chicago area met to explore how different sources of stress – from the cells to the community – impact diabetes outcomes. Presenters discussed the consequences of stress arising from mutant proteins, obesity, sleep disturbances, environmental pollutants, COVID-19, and racial and socioeconomic disparities. This symposium showcased the latest diabetes research and highlighted promising new treatment approaches for mitigating stress in diabetes