Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers.

OBJECTIVE: Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory-amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EGNR) and autonomic nervous system (ANS) responses versus steroidal hormones and controls in healthy adults is reported. METHODS: Eight males and 8 females randomly received aerosolized control (propylene glycol) and study drugs (fasedienol, 17ß-estradiol, progesterone, cortisol, and testosterone, 0.4 µg each in propylene glycol) onto the nasal septum mucosal lining at 30-min intervals over 2 sessions. EGNR was continuously monitored; autonomic parameters were recorded before and after administration. RESULTS: Fasedienol significantly increased EGNR amplitude (males: 5.0 vs. 0.6 mV, p < 0.001; females:5.7 vs. 0.6 mV, p < 0.001), and rapidly reduced respiratory rate (p < 0.05), heart rate (p < 0.01), and electrodermal activity (p < 0.05) versus control. EGNR and ANS responses after steroidal hormone administration were similar to control. 81% reported feeling less tense/more relaxed after receiving fasedienol, but not after receiving either control or steroidal hormones. CONCLUSIONS: Intranasal fasedienol, but not control or steroidal hormones, activated EGNR and rapidly reduced ANS responses, consistent with sympatholytic effects. Combined with subjective reports, results suggest fasedienol may provide acute relief in anxiety conditions.

Vortioxetine versus placebo in major depressive disorder comorbid with social anxiety disorder.

BACKGROUND: Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD) are highly comorbid, yet the combined condition has not been subject to any placebo-controlled treatment trials. This study reports a trial of vortioxetine, an antidepressant that has also shown benefit in Generalized Anxiety Disorder (GAD), in patients meeting DSM-5 criteria for both MDD and SAD. METHODS: The study was a 12-week double-blind, placebo-controlled comparison of vortioxetine 10-20 mg/day or placebo administered on a 1:1 ratio. The study was designed to include 40 male or female outpatients aged 18-70 years. The primary endpoint was the "composite" Clinical Global Impression of Improvement (CGI-I) responder rate, factoring in improvement in both MDD and SAD features. Major secondary outcome measures were changes on the Montgomery Asberg Depression Rating Scale (MADRS) and Liebowitz Social Anxiety Scale (LSAS). RESULTS: On the composite CGI-I, 10 of 20 (50%) vortioxetine and six of 20 (30%) placebo-treated patients were rated as responders, a non-significant difference. However, vortioxetine-treated patients did show significantly greater improvement than those on placebo on both the MADRS (effect size 0.672) and LSAS (effect size 0.714). Efficacy in depression was seen before improvement in SAD. Adverse effects were similar to those previously reported. CONCLUSIONS: In this preliminary trial vortioxetine appears safe and effective for patients with MDD comorbid with SAD, with robust effect sizes on dimensional measures of both depression and social anxiety, but failure to separate from placebo on the primary outcome measure of composite responder rate. More studies of patients with comorbid conditions are needed, as this mirrors what is often seen in clinical practice.

Effect of as-needed use of intranasal PH94B on social and performance anxiety in individuals with social anxiety disorder.

BACKGROUND: There are no medications approved for as-needed use for feared situations for individuals with social anxiety disorder (SAD). In the present study, intranasal PH94B was provided for use as needed during stressful events. METHODS: Twenty-two subjects were randomized (double-blind) to 2 weeks of treatment with intranasal PH94B or placebo. Following self-administration of medication prior to a feared event, peak levels of anxiety were recorded using the Subjective Units of Distress Scale (SUDS). After 2 weeks, subjects were crossed over to the opposite treatment for 2 weeks. Average peak SUDS during treatment with PH94B and placebo were compared using a paired t-test. RESULTS: Significant differences in favor of PH94B were found on the primary outcome measure: mean peak SUDS change from baseline for all subjects receiving PH94B was 15.6 points versus 8.3 points for placebo (paired t = 3.09, P = .006, effect size of .658). PH94B showed less superiority over placebo when placebo was given second rather than first, likely due to a carryover effect. Looking between groups at just the first 2 weeks of treatment, PH94B also showed trend superiority to placebo on the Liebowitz Social Anxiety Scale (LSAS) (P = .07) and a significant difference on the Patient Global Impression of Change (P = .024) and the LSAS Avoidance subtotal (P = .02). CONCLUSIONS: While further study is needed, these results, combined with earlier findings, suggest that PH94B could represent a useful as-needed treatment for SAD, and continue to validate the nasal chemosensory system as a novel mechanism for medication delivery.

Producing comparable cost and quality results from all-payer claims databases.

OBJECTIVES: To describe how all-payer claims databases (APCDs) can be used for multistate analysis, evaluating the feasibility of overcoming the common barrier of a lack of standardization across data sets to produce comparable cost and quality results for 4 states. This study is part of a larger project to better understand the cost and quality of healthcare services across delivery organizations. STUDY DESIGN: Descriptive account of the process followed to produce healthcare quality and cost measures across and within 4 regional APCDs. METHODS: Partners from Colorado, Massachusetts, Oregon, and Utah standardized the calculations for a set of cost and quality measures using 2014 commercial claims data collected in each state. This work required a detailed understanding of the data sets, collaborative relationships with each other and local partners, and broad standardization. Partners standardized rules for including payers, data set elements, measure specifications, SAS code, and adjustments for population differences in age and gender. RESULTS: This study resulted in the development of a Uniform Data Structure file format that can be scaled across populations, measures, and research dimensions to provide a consistent method to produce comparable findings. CONCLUSIONS: This study demonstrates the feasibility of using state-based claims data sets and standardized processes to develop comparable healthcare performance measures that inform state, regional, and organizational healthcare policy.

A 12-Week Double-Blind, Placebo-Controlled, Flexible-Dose Trial of Vilazodone in Generalized Social Anxiety Disorder.

OBJECTIVE: To examine the efficacy, safety, and tolerability of vilazodone for subjects (aged 18-75 years) with generalized social anxiety disorder. METHOD: Forty-four subjects with generalized social anxiety disorder (DSM-IV-TR criteria) were randomized to vilazodone or placebo in a 12-week double-blind, flexible-dose trial. Change from baseline to endpoint on the Liebowitz Social Anxiety Scale (LSAS) was the primary outcome measure. Secondary outcome measures included response and remission rates and changes in depression and anxiety. Data were collected between November 2012 and April 2014. The study was conducted at a private clinical trials facility in New York, New York. RESULTS: The mean baseline LSAS score was 91.9 (SD = 17.5) and the mean Clinical Global Impressions-Severity scale score was 5.3 (SD = 0.56), indicating marked to severe illness. There were no significant baseline differences in severity of social anxiety between the treatment groups. At the end of treatment, in the intent-to-treat sample (n = 39), the vilazodone group had improved significantly more than the placebo group by 14.3 points on the LSAS (t = 1.80, P = .04, one-tail test) (Cohen d = 0.58). CONCLUSIONS: The findings suggest that vilazodone may be a promising treatment for social anxiety disorder. Further study is needed given the limited sample size. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01712321.

Staying on track: a cluster randomized controlled trial of automated reminders aimed at increasing human papillomavirus vaccine completion.

OBJECTIVES: To evaluate whether automated reminders increase on-time completion of the three-dose human papillomavirus (HPV) vaccine series. METHODS: Ten reproductive health centers enrolled 365 women aged 19-26 to receive dose one of the HPV vaccine. Health centers were matched and randomized so that participants received either routine follow-up (control) or automated reminder messages for vaccine doses two and three (intervention). Intervention participants selected their preferred method of reminders - text, e-mail, phone, private Facebook message, or standard mail. We compared vaccine completion rates between groups over a period of 32 weeks. RESULTS: The reminder system did not increase completion rates, which overall were low at 17.2% in the intervention group and 18.9% in the control group (p=0.881). Exploratory analyses revealed that participants who completed the series on-time were more likely to be older (OR=1.15, 95% CI 1.01-1.31), report having completed a four-year college degree or more (age-adjusted OR=2.51, 95% CI 1.29-4.90), and report three or more lifetime sexual partners (age-adjusted OR=3.45, 95% CI 1.20-9.92). CONCLUSIONS: The study intervention did not increase HPV vaccine series completion. Despite great public health interest in HPV vaccine completion and reminder technologies, completion rates remain low.

Effect of an acute intranasal aerosol dose of PH94B on social and performance anxiety in women with social anxiety disorder.

OBJECTIVE: Although social anxiety disorder is a common and sometimes disabling condition, there are no approved treatments that can be used on an as-needed basis. The authors examined the acute use of PH94B, an intranasally administered neurosteroidal aerosol, for the acute management of the symptoms of social anxiety disorder. METHOD: The authors conducted a phase 2, multicenter, randomized, double-blind, placebo-controlled, single-dose study of PH94B. Ninety-one women 19-60 years of age with generalized social anxiety disorder received placebo intranasal spray (single-blind) 15 minutes before laboratory-simulated public speaking and social interaction challenges. Patients who experienced significant distress during at least one challenge returned 1 week later to receive either intranasal PH94B or placebo aerosol spray (double-blind) before repeat challenges. RESULTS: Patients who received PH94B during the second set of challenges had a significantly greater decrease in mean Subjective Units of Distress scores during the public speaking and social interaction challenges compared with the first set of challenges, than did patients who received placebo for both sets of challenges. A significantly greater proportion of the PH94B group were much or very much improved from the first to the second sets of challenges compared with the placebo group (75% and 37%, respectively). The side effects of PH94B were benign. CONCLUSIONS: PH94B may be a novel, effective, and well-tolerated acute treatment for performance and social anxiety in women with social anxiety disorder.