Placebo Spray Research Articles

Evaluation of PHR160 Spray Effect on Improvement of Lung Function, Asthma Severity and Exacerbation in Severe Asthmatic Patients

Pinen Hydronoplacton Ribonucleic acid (PHR160) medicine contains compounds that can be useful in the recovery of respiratory patients. The aim of this study was to determine the effect of PHR spray on improving lung function, severity and asthma attacks in patients with severe asthma. This study is a pioneering interventional study (pilot study) conducted during the years 2021-2022 on patients with severe asthma resistant to treatment who referred to the lung clinic of Imam Khomeini, Golestan Hospitals and the private practice of lung specialists of this academic center. The study includes two groups of patients with asthma, both groups were given the usual treatment according to the stage of the disease, in addition, the intervention group was given two puffs of PHR spray every eight hours, and the control group was given a placebo spray with the same dose. Before and after the intervention, GSK 2002 questionnaire, six-minute walk distance (6MWD) and spirometry tests were completed. Among of 60 patients, 27 (45%) were male. The mean age of the patients was 44.33±6.94 years. Based on findings, the forced vital capacity (FVC) and forced expiratory flow between 25% and 75% (FEF 25-75%) were significantly better in the intervention group than the control group (P<0.001 and P=0.019, respectively), but there was a statistically remarkable difference between the two groups in terms of forced expiratory volume (FEV1) and FEV1/FVC (P=0.505, P=0.575, respectively). In addition, the GSK questionnaire score in the intervention group was higher than the control group (P<0.001), however there is no significant difference between the two intervention groups in terms of the 6MWD test and the number of exacerbation (P=0.114 and P=0.09, respectively). It is generally concluded that PHR160 spray can lead to improvement of spirometry parameters and severity of disease in severe asthma patients by affecting small airways.

Efficacy of Local Anesthesia for Radial Artery Puncture Pain: A Systematic Review and Network Meta-Analysis.

We performed a systematic review and network meta-analysis (NMA) to assist clinicians in determining the optimal patient-specific method of analgesia during radial artery puncture by comparing radial artery puncture procedural pain. We included randomized controlled trials that assessed the prophylactic efficacy of local anesthesia for radial artery puncture-associated pain. We searched the Medical Literature Analysis and Retrieval System Online in January 2023, the Cochrane Central Register of Controlled Trials in January 2023, the Excerpta Medica Database in December 2022, the World Health Organization International Clinical Trials Platform Search Portal in January 2023, and ClinicalTrials.gov in January 2023. We synthesized the pain scores (0-100 scale) using the frequentist random-effects NMA model. We evaluated the confidence in each outcome using the CINeMA tool (https://cinema.ispm.unibe.ch/). We conducted an NMA of 1,619 patients across 14 studies on pain scores during radial artery puncture-related procedures for 12 interventions. Compared with placebo, mepivacaine infiltration and lidocaine spray probably reduce pain (mean difference (MD): -47.67, 95% confidence interval (CI): -61.45 to -33.89, confidence rating (CR): moderate; MD: -27.38, 95% CI: -37.53 to -17.22, CR: moderate). Of the 32 studies included, none reported systemic adverse events, such as anaphylaxis or local anesthetic systemic toxicity, or severe local adverse events. In conclusion, mepivacaine infiltration and lidocaine spray probably reduce the pain associated with radial artery puncture more than other local anesthesia.

Effect of Coenzyme Q10 on early wound healing after recession coverage surgery with the modified coronally advanced tunnel technique and a connective tissue graft: A 6-month, triple-blinded, randomized, placebo-controlled pilot trial

ObjectivesCoenzyme Q10 (CoQ10) or ubiquinone is one of a cell’s most important electron carriers during oxidative phosphorylation and many other cellular processes. As a strong anti-oxidant with further anti-inflammatory effects CoQ10 is of potential therapeutical value. The aim of this randomized controlled clinical trial was to investigate the effect of topical CoQ10 on early wound healing after recession coverage surgery using the modified coronally advanced tunnel (MCAT) and palatal connective tissue graft (CTG).Materials and methodsThirty patients with buccal gingival recessions were evaluated after being randomly allocated to: 1) MCAT and CTG with topical application of a coenzyme Q10 spray for 21 days or 2) MCAT and CTG with placebo spray. Wound healing was evaluated by the early wound healing index (EHI). Patient-reported pain was analyzed by a 100-mm visual analogue scale (VAS) at day 2, 7, 14 and 21 post-surgically. Mean recession coverage, gain of keratinized tissue and esthetic outcomes were assessed at 6 months.ResultsEHI and pain scores showed no significant differences. Time to recovery defined as VAS<10 mm was shorter in the test group. Mean root coverage after 6 months was 84.62 ± 26.57% and 72.19 ± 26.30% for test and placebo, p=0.052. Complete root coverage was obtained in 9 (60%) test and in 2 (13.3%) placebo patients. Increase in keratinized tissue width and esthetical outcomes were similar for both groups.ConclusionCoQ10 had no significant effect on early wound healing and on mean root coverage after 6 months.Clinical relevanceEarly wound healing: in young healthy patients with no inflammatory oral conditions topical CoQ10 does not improve early healing.

Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase

Insulin action in the human brain modulates eating behaviour, whole-body metabolism and body fat distribution1,2. In particular, brain insulin action increases whole-body insulin sensitivity, but these studies were mainly performed in lean men3,4. Here we investigate metabolic and hypothalamic effects of brain insulin action in women with a focus on the impact of menstrual cycle (ClinicalTrials.gov registration: NCT03929419).Eleven women underwent four hyperinsulinemic–euglycemic clamps, two in the follicular phase and two in the luteal phase. Brain insulin action was introduced using nasal insulin spray5–7 and compared to placebo spray in a fourfold crossover design with change in glucose infusion rate as the primary endpoint. Here we show that during the follicular phase, more glucose has to be infused after administration of nasal insulin than after administration of placebo. This remains significant after adjustment for blood glucose and insulin. During the luteal phase, no significant influence of brain insulin action on glucose infusion rate is detected after adjustment for blood glucose and insulin (secondary endpoint). In 15 other women, hypothalamic insulin sensitivity was assessed in a within-subject design by functional magnetic resonance imaging with intranasal insulin administration8. Hypothalamus responsivity is influenced by insulin in the follicular phase but not the luteal phase.Our study therefore highlights that brain insulin action improves peripheral insulin sensitivity also in women but only during the follicular phase. Thus, brain insulin resistance could contribute to whole-body insulin resistance in the luteal phase of the menstrual cycle.

Relieving psychological stress and improving sleep quality by bergamot essential oil use before bedtime and upon awakening: A randomized crossover trial

ObjectivesThe COVID-19 pandemic increased psychological stress and decreased sleep quality, especially among young people. Aromatherapy alleviates psychological stress, and bergamot essential oil helps improve depression. This study aimed to verify whether bergamot essential oil use alleviates psychological stress due to the COVID-19 pandemic and improves sleep quality and morning wakefulness. DesignA placebo-controlled, randomized, open-label, two-arm, two-period crossover trial. InterventionsEach intervention period was 1 week, with a 1-week washout period between the two periods. Participants used a bergamot or placebo spray before bedtime and upon awakening in each period. Main outcome measuresThe primary outcome measures were sleep quality and morning wakefulness, assessed using the Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). The secondary outcome measures were depression, anxiety, and stress, assessed using the Depression Anxiety Stress Scales-21 (DASS-21). ResultsA total of 48 university students participated in the study. A significant improvement was observed in “sleepiness on rising,” “refreshing on rising,” and “sleep length” in the bergamot group. Additionally, a significant improvement was observed in depression, anxiety, and stress. ConclusionUsing bergamot essential oil before bedtime helps relax the mind and body and provides sound sleep. It also improves mood and wakefulness when used upon awakening. Using aromatic essential oils is expected to relieve psychological stress and improve sleep quality and morning wakefulness.

Impact of Vitamin D Therapy on C-Reactive Protein, Ferritin, and IL-6 Levels in Hospitalised Covid-19 Patients

Abstract Vitamin D insufficiency is associated with poor prognosis in COVID-19 patients. Vitamin D supplementation is related to improved clinical outcomes in terms of intensive care unit admission and death, particularly in individuals with moderate-to-severe forms of COVID-19. The placebo-controlled five-day study was performed on 99 hospitalised COVID-19 patients with vitamin D insufficiency randomised into two groups. Vitamin D in the form of a sublingual sprayable microemulsion was given three times daily (daily dose 12,000 IU) to 51 patients with blood 25(OH)D levels below 30 ng/ml. Forty-eight patients in the control group received a placebo spray in the same daily regimen. Intention-to-treat (ITT) analysis and pre-protocol analysis were used to verify the impact of 25(OH)D level elevation on inflammatory markers. There was a statistically significant increase by 8.7 ± 7.6 ng/ml in 25(OH)D level from the baseline level of 15.6 ± 6.5 ng/ml in the case group. Individuals with moderately severe disease showed negative correlation between changes in 25(OH)D and C-reactive protein (CRP) levels in both ITT and pre-protocol analysis (p &lt; 0.05). Mild and severe cases showed no statistical significance in CRP levels. There were no statistically significant changes in ferritin and IL-6 levels in ITT and pre-protocol analysis. In conclusion, high-dose vitamin D therapy was accompanied by significant decrease in CRP levels in COVID-19 patients with a moderate to severe illness.

302-OR: How Menstrual Cycle Impacts Brain Insulin Action—Results from Young Women

The human brain is an insulin-sensitive organ that modulates whole-body glucose metabolism and adiposity. In case of brain insulin resistance, this regulation is disturbed. In the periphery, insulin sensitivity varies along the menstrual cycle, while the effects on brain insulin action are still unknown. We here investigated the impact of menstrual cycle on brain insulin sensitivity of the human hypothalamus and on brain-derived modulation of peripheral metabolism. In 26 naturally cycling women (age 19-29 years, BMI 18-24 kg/m2), brain insulin action was assessed in both the follicular and the luteal phase using nasal application of 160 U insulin. In fifteen women, we assessed hypothalamic insulin responsiveness by functional MRI combined with nasal insulin. In eleven women, brain-derived modulation of peripheral insulin sensitivity was studied by hyperinsulinemic euglycemic clamps combined with insulin vs placebo spray. Only in the follicular phase, nasal insulin significantly decreased hypothalamic blood flow (p=0.02), indicating proper brain insulin action. In the luteal phase, insulin induced no such effect (p=0.6). During hyperinsulinemic euglycemic clamps in the follicular phase, more glucose had to be infused after insulin compared to placebo spray. This difference remained significant after adjustment for circulating glucose and insulin (p&amp;lt;0.0001), which was not the case in the luteal phase (p=0.1). High estradiol/progesterone ratio, as present during the follicular phase, was linked to a stronger effect of insulin spray on glucose infusion rates than placebo. Brain insulin sensitivity is a regulated process that can rapidly adapt to changing physiologic requirements, as through the menstrual cycle. In the luteal phase, we detected hypothalamic insulin resistance, which likely contributed to the lacking modulation of peripheral insulin sensitivity through brain insulin delivery. Thus, brain insulin resistance could contribute to whole-body insulin resistance in the luteal phase. Disclosure J.Hummel: None. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. H.Häring: None. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. A.Peter: None. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. S.Kullmann: None. M.Heni: Advisory Panel; Boehringer-Ingelheim, Sanofi, Research Support; Boehringer Ingelheim Inc., Speaker's Bureau; Lilly, Bayer Inc., Sanofi, Boehringer-Ingelheim, Novo Nordisk, Amryt Pharma Plc. C.Benkendorff: None. L.Fritsche: None. K.Prystupa: Other Relationship; Berlin-Chemie AG. A.Vosseler: None. S.Gancheva: Consultant; Novo Nordisk, Bayer Inc. S.Trenkamp: None. A.L.Birkenfeld: None. H.Preissl: None. Funding German Federal Ministry of Education and Research

The effect of using vapocoolant spray for pain reduction in arteriovenous fistula cannulation among patients undergoing hemodialysis: A randomized control trial

AimThe aim of this study was to assess the effects of alkane vapocoolant spray in reducing pain during arteriovenous access cannulation in adult patients undergoing hemodialysis. BackgroundDeveloping and applying various approaches for pain relief remain important responsibility for nurses. MethodsThis study was designed as an experimental study with a cross-over design. Thirty-eight patients on hemodialysis volunteered to undergo cannulation of their arteriovenous access, after the application of vapocoolant or placebo spray or no intervention. Subjective and objective pain levels were assessed, along with various physiological parameters pre- and post-cannulation. ResultsStatistically significant between-group differences were observed in subjective pain at the venous (F = 4.97, p = 0.009) and arterial (F = 6.91, p = 0.001) puncture sites. The mean arterial site subjective pain scores were 4.45 ± 1.31 (no treatment), 4.04 ± 1.82 (placebo), and 2.98 ± 1.53 (vapocoolant spray). Significant between-group differences were observed in objective pain scores during arteriovenous fistula puncture (F = 5.13, p = 0.007). The mean objective pain scores after arteriovenous fistula puncture were 3.25 ± 2.66 (no treatment), 2.17 ± 1.76 (placebo), and 1.78 ± 1.66 (vapocoolant spray). Post-hoc test results indicated vapocoolant spray application was associated with significantly lower pain scores than no treatment or placebo. Patient blood pressure and heart rate recordings did not differ among the interventions. ConclusionVapocoolant application was significantly more effective than the placebo or no treatment in reducing the pain of cannulation in adult patients undergoing hemodialysis.

Cooling spray or lidocaine spray and needle insertion pain in hemodialysis patients: an open-label cross-over randomized clinical trial

BackgroundThe needle insertion pain to perform hemodialysis is the main challenge and a common problem that requires pain management techniques for patients’ comfort.AimThis study aimed to compare the effects of cooling and lidocaine sprays on needle insertion pain in hemodialysis patients.MethodsIn this randomized cross-over clinical trial study, the hemodialysis patients were selected through convenience sampling according to inclusion criteria and randomly assigned to three intervention groups using the block randomization method. Each patient received three interventions in a cross-over design: Cooling spray or 10% lidocaine spray or placebo spray. There was a 2-week wash-out time between each intervention. The pain score was measured four times for each patient by the Numerical Rating Scale.ResultsForty-one hemodialysis patients were included. The results showed a significant interaction between time and group (p < 0.05), so only observations of time 1 with adjustment for baseline values were used to evaluate the effect of the intervention. Patients receiving cooling spray reported 2.29 less pain score on average compared to placebo (B=-2.29, 95% CI: -4.17 to -0.43; p < 0.05); Also, patients receiving cooling spray reported a 1.61 lower pain score than those receiving lidocaine spray, but this difference was not statistically significant (95% CI: -0.26 to 3.48; p > 0.05).ConclusionThe cooling spray was effective in reducing the needle insertion pain. Although it was impossible to compare the pain scores at different times and following different interventions, the present study results can help supplement the existing knowledge regarding cooling and lidocaine sprays.

Comparison of the Effect of Injectable Tranexamic Acid and Inhaled Desmopressin in Controlling Bleeding and Ecchymosis in Open Rhinoplasty.

Bleeding during rhinoplasty surgery has a negative effect on the quality of surgery; so, it is important to reduce bleeding during rhinoplasty. We aimed to evaluate the effect of injectable tranexamic acid (TXA) and nasal spray of desmopressin (DDAVP) on reduction in intraoperative bleeding and ecchymosis after open rhinoplasty. In a Randomized Clinical Trial ( RCT) prepared since 2020 to 2021 in Razi Hospital and Imam Khomeini Hospital, Tehran, Iran on 42 patients who underwent open rhinoplasty were divided into three groups. In the first group, TXA was injected one hour before surgery at a dose of 10 mg / kg with a placebo inhalation spray. In the second group, DDAVP was administered as a nasal spray at a dose of 40 mcg with a placebo injection. The third group received a placebo spray and placebo injection. All required data were gathered and analyzed. In TXA group and DDAVP groups, the volume of bleeding during surgery significantly (P=0.022) decreased compared to placebo group, also, the quality of the surgical field and the surgeon's satisfaction significantly (P=0.007) improved compared to the placebo group but not with each other. Unlike placebo group, there were no reports of postoperative bleeding in the TXA and DDAVP groups. Duration of surgery, ecchymosis on the day after surgery and coagulation tests before and after surgery were not significantly different in three groups. Use of DDAVP and TXA can both reduce the amount of bleeding during surgery and postoperative bleeding in rhinoplasty and improve the quality of the surgical field and the surgeon 's satisfaction during surgery.

Sex differences in central insulin action: Effect of intranasal insulin on neural food cue reactivity in adults with normal weight and overweight

Background/ObjectivesCentral insulin action influences cognitive processes, peripheral metabolism, and eating behavior. However, the contribution of obesity and sex on central insulin-mediated neural food cue processing still remains unclear.Subjects/MethodsIn a randomized within-participant design, including two visits, 60 participants (30 women, BMI 18–32 kg/m2, age 21–69 years) underwent a functional MRI task measuring blood oxygen level-dependent (BOLD) signal in response to visual food cues after intranasal insulin or placebo spray administration. Central insulin action was defined as the neural BOLD response to food cues after insulin compared to placebo administration. Afterwards, participants were asked to rate the food cues for desire to eat (i.e., wanting rating). For statistical analyses, participants were grouped according to BMI and sex.ResultsFood cue reactivity in the amygdala showed higher BOLD activation in response to central insulin compared to placebo. Furthermore, women with overweight and obesity and men of normal weight showed higher BOLD neural food cue responsivity to central insulin compared to placebo. Higher central insulin action in the insular cortex was associated with better peripheral insulin sensitivity and higher cognitive control. Moreover, central insulin action in the dorsolateral prefrontal cortex (DLPFC) revealed significant sex differences. In response to central insulin compared to placebo, men showed lower DLPFC BOLD activity, whereas women showed higher DLPFC activity in response to highly desired food cues. On behavioral level, central insulin action significantly reduced hunger, whereas the desire to eat, especially for low caloric food cues was significantly higher with central insulin than with placebo.ConclusionsObesity and sex influenced the central insulin-mediated neural BOLD activity to visual food cues in brain regions implicated in reward and cognitive control. These findings show that central insulin action regulates food response differentially in men and women, which may have consequences for metabolism and eating behavior.

Comparison of cold spray and shotblocker to reduce intramuscular injection pain: A randomized controlled trial.

It is important to identify effective, easy-to-use and cost-effective non-pharmacological methods in the management of pain caused by medical interventions. The purpose of this study is to compare the effects of cold spray and ShotBlocker on pain in adults in reducing pain caused by intramuscular injection in the adult emergency department. This is a randomized controlled trial with two experimental groups, two placebo groups and a control group. The study was conducted on 195 adults who received diclofenac sodium injections. In the study, the injection procedure was performed by following the same injection protocol in all five groups. In the injection process, cold spray or ShotBlocker was used in the intervention groups based on the group, and cold spray with distilled water or the smooth surface of the ShotBlocker was used in the placebo groups. Following the injection, the pain caused by the injection was evaluated using the Visual Analog Scale. The study was completed with the remaining 195 patients. In the study, the average pain scores due to injection of the individuals in the cold spray group were lower than those of the control group (p<0.05). There was no statistically significant difference between the pain score averages due to injection of the individuals in the ShotBlocker group and cold spray, control, ShotBlocker placebo and cold spray placebo groups. The routine use of a fast-acting, cost-effective and easy-to-use method, cold spray, to reduce pain in the intramuscular injection will be beneficial in increasing patient satisfaction and quality of care.

ON-ICE trial: Investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder–Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial

IntroductionAlthough alcohol dependence (AD) is highly prevalent, only few medications are approved for its treatment. While currently approved medications, such as naltrexone (NTX), reduce craving and relapse risk to a...

Throat Spray With Blended Essential Oils Promotes Healthy Lung Function Among Women: A Randomized, Double Blinded, Placebo Controlled Clinical Trial.

IntroductionThere are numerous internal and external environmental threats to lung health. Compromised respiratory health can affect a person's quality of life. This clinical trial evaluated the effects of Teramune Bronchus on lung health among healthy adult women.MethodsThe participants were women, aged 18 - 60 years old (n = 35). They sprayed either the proprietary essential oil based blended product (Teramune Bronchus) or a placebo into their throats 4-6 times per day during waking hours for 3 days. There was a baseline survey before using the spray and then follow-up data were collected at the end of day 3. The three primary outcomes for this study include a total bronchial symptom score, the chest domain in the Wisconsin Upper Respiratory Symptom Scale (WURSS), and subjective bronchial wellbeing.ResultsOn day 3, the bronchial health of the participants who received the throat spray had significantly larger change scores when compared those with the placebo spray. All chest-related symptoms were resolved fully by the end of the trial for the participants who used Teramune. Participants using the intervention were almost twice as likely to say they felt better and believed the product helped them achieve lung health.ConclusionThis study provides evidence that the use of Teramune Bronchus supports respiratory health. Teramune Bronchus boosts respiratory health among healthy women through the use of plant-based essential oils.

Effectiveness of lidocaine spray on radial arterial puncture pain: A randomized double-blind placebo controlled trial.

Radial arterial puncture is a painful procedure. The aim of this study was to evaluate the effect of lidocaine spray (10%) on pain associated with radial artery blood withdrawal for arterial blood gas analysis. This randomized, controlled, double-blind study was performed between December 2018 and September 2019. Before radial arterial puncture, 10% lidocaine or placebo spray was applied to each patient by the attending physician, who was blinded with regard to random assignment. The spray was administered six times on the site from a distance of 5cm. After waiting for 5min, a radial arterial puncture was performed routinely. The pain levels of patients during radial arterial puncture and 5min after puncture were evaluated with the visual analog scale (VAS). The Wilcoxon test was used to compare pain scores during puncture. The research was performed with 67 patients (34 patients in the lidocaine group, 33 patients in the placebo group) who were admitted to the emergency department and required ABG analysis. Forty-three patients were men, and 24 were women. The ages of the patients ranged between 19 and 86years, and the mean (± standard deviation) age was 56.3±16.6years. Pain levels, as measured by VAS, were significantly lower in the lidocaine group (24.00mm IQR:[14.75-33.75]) compared with the placebo group (33.00mm IQR:[22.00-61.50]) during radial arterial puncture (p=0.011). The level of pain perceived during radial arterial puncture was significantly lower in those who were administered lidocaine spray. Lidocaine spray application can be used in pain management related to radial arterial puncture.

Effect of Sleep Disturbance on Efficacy of Esketamine in Treatment-Resistant Depression: Findings from Randomized Controlled Trials.

PurposeTo evaluate the relationship of sleep disturbance to the antidepressant effects of esketamine.Materials and MethodsTwo double-blind, 4-week studies randomized adults with treatment-resistant depression (TRD) to placebo or esketamine nasal spray, each with newly initiated antidepressant. Sleep was assessed using Montgomery–Åsberg Depression Rating Scale (MADRS) item 4. Change in response (≥50% decrease in MADRS total score) and remission (total MADRS score ≤12) at day 28 was examined by presence/absence of baseline sleep disturbance using logistic regression models. Impact on reported sleep disturbance (MADRS item 4 score) was examined using ANCOVA models.ResultsAt baseline, most patients reported disturbed sleep – moderate/severe (65.3%, 369/565), mild (25.3%, 143/565), or none/slightly (9.4%, 53/565) – with similar distribution between treatment groups. A higher proportion of esketamine-treated patients achieved response (OR = 2.05; 95% CI: 1.40–3.02; P < 0.001) and remission (OR = 1.81; 95% CI: 1.23–2.66; P = 0.003) at day 28 compared to antidepressant plus placebo, regardless of presence/severity of sleep disturbance. Consistent with this, sleep (MADRS item 4 score) improved in both groups after the first dose, more so with esketamine by day 8 (between-group difference: P ≤ 0.02 at all time points). Across both treatment groups, 1-point improvement in sleep at day 8 increased the probability of antidepressant response on day 28 by 26% (OR = 1.26, 95% CI: 1.12–1.42; P < 0.001), and remission by 28% (OR = 1.28, 95% CI: 1.14–1.43; P < 0.001).ConclusionAntidepressant efficacy of esketamine was demonstrated in patients with TRD, regardless of the presence of sleep disturbance. After 8 days of treatment and thereafter, significantly more esketamine-treated patients reported improvement in sleep versus antidepressant plus placebo.

Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study

BackgroundEsketamine nasal spray (Spravato) in conjunction with oral antidepressants (ADs) is approved in the European Union, United States, and other markets for treatment-resistant depression (TRD). Efficacy, safety, and tolerability of esketamine nasal spray in Japanese patients with TRD needs to be assessed.MethodsThis Phase 2b, randomized, double-blind (DB), placebo-controlled study was conducted in adult Japanese patients with TRD meeting the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) criteria of major depressive disorder with nonresponse to ≥ 1 but < 5 different ADs in the current episode at screening. Patients were treated with a new oral AD for 6 weeks (prospective lead-in phase); nonresponders were randomized (2:1:1:1) to placebo or esketamine (28-, 56-, or 84-mg) nasal spray along with the continued use of AD for 4 weeks (DB induction phase). Responders (≥50% reduction from baseline in the Montgomery-Asberg Depression Rating Scale [MADRS] total score) from the DB induction phase continued into the 24-week posttreatment phase and patients who relapsed could participate in a 4-week open-label (OL) second induction (flexibly-dosed esketamine). The primary efficacy endpoint, change from baseline in the MADRS total score at Day 28 in the DB induction phase, was based on mixed-effects model using repeated measures pairwise comparisons using a Dunnett adjustment.ResultsOf the 202 patients randomized in the DB induction phase (esketamine [n = 122] or placebo [n = 80]), the MADRS total scores decreased from baseline to Day 28 of the DB induction phase (− 15.2, − 14.5, − 15.1, and − 15.3 for esketamine 28 mg, 56 mg, 84 mg, and placebo groups, respectively), indicating an improvement in depressive symptoms; however, the difference between the esketamine and placebo groups was not statistically significant. The most common treatment-emergent adverse events during the DB induction phase in the combined esketamine group (incidences ranging from 12.3 to 41.0%) were blood pressure increased, dissociation, dizziness, somnolence, nausea, hypoaesthesia, vertigo, and headache; the incidence of each of these events was > 2-fold higher than the corresponding incidence in the placebo group.ConclusionsEfficacy of esketamine plus oral AD in Japanese TRD patients was not established; further investigation is warranted. All esketamine doses were safe and tolerated.Trial registrationClinicalTrials.gov Identifier: NCT02918318. Registered: 28 September 2016.

A randomized placebo-controlled intranasal oxytocin study on first impressions and reactions to social rejection

Oxytocin is central to pair-bonding in non-human animals. We assessed effects of intranasal oxytocin on bond formation between two opposite-sex strangers. In a double-blind placebo-controlled design, 50 pairs of one man and one woman received oxytocin or placebo spray intranasally. After treatment, they played a social interaction game, followed by tasks designed to measure first impressions of the opposite-sex co-participant, and a virtual ball-tossing game (cyberball), designed to measure reactions to rejection by the co-participant. We found no evidence that intranasal oxytocin can improve first impressions of an opposite-sex stranger, and some Bayesian support against this hypothesis. For rejection sensitivity, we observed a sex-and-context-dependent drug effect on post-ostracism mood ratings, consistent with recent studies indicating that interindividual variation and social context can interact with intranasal oxytocin effects. Further research is needed to determine the generalisability of these findings, i.e. if oxytocin can improve first impressions in humans under different conditions.

The effect of esketamine in patients with treatment-resistant depression with and without comorbid anxiety symptoms or disorder.

BackgroundComorbid anxiety is generally associated with poorer response to antidepressant treatment. This post hoc analysis explored the efficacy of esketamine plus an antidepressant in patients with treatment‐resistant depression (TRD) with or without comorbid anxiety.MethodsTRANSFORM‐2, a double‐blind, flexible‐dose, 4‐week study (NCT02418585), randomized adults with TRD to placebo or esketamine nasal spray, each with a newly‐initiated oral antidepressant. Comorbid anxiety was defined as clinically noteworthy anxiety symptoms (7‐item Generalized Anxiety Disorder scale [GAD‐7] score ≥10) at screening and baseline or comorbid anxiety disorder diagnosis at screening. Treatment effect based on change in Montgomery–Åsberg Depression Rating Scale (MADRS) total score, and response and remission were examined by presence/absence of comorbid anxiety using analysis of covariance and logistic regression models.ResultsApproximately 72% (162/223) of patients had baseline comorbid anxiety. Esketamine‐treated patients with and without anxiety demonstrated significant reductions in MADRS (mean [SD] change from baseline at day 28: −21.0 [12.51] and −22.7 [11.98], respectively). Higher rates of response and remission, and a significantly greater decrease in MADRS score at day 28 were observed compared to antidepressant/placebo, regardless of comorbid anxiety (with anxiety: difference in LS means [95% CI] −4.2 [−8.1, −0.3]; without anxiety: −7.5 [−13.7, −1.3]). There was no significant interaction of treatment and comorbid anxiety (p = .371). Notably, in the antidepressant/placebo group improvement was similar in those with and without comorbid anxiety.ConclusionPost hoc data support efficacy of esketamine plus an oral antidepressant in patients with TRD, regardless of comorbid anxiety.

10% lidocaine spray for pain control during intrauterine device insertion: a randomised, double-blind, placebo-controlled trial

BackgroundVarious medications have been investigated for their efficacy in pain reduction during intrauterine device (IUD) insertion, but there is currently no standard recommendation. This study aimed to investigate the efficacy...