Gustafsonmcdowell9055

ne (dose 56-84 mg once-weekly or once-every-other-week) plus an oral AD demonstrated NNT values less then 10 for relapse and/or maintenance of remission in favor of esketamine+AD vs AD+placebo, a NNT of 4 was observed for outcome of relapse in patients with stable response at the time of randomization (relapse rates were 25.8% vs 57.6%, respectively). In the maintenance study, discontinuation rates due to an AE (2.6% vs 2.1%) yielded a non-significant NNH value of 178. CONCLUSION The low NNT values less then 10 for efficacy outcomes suggest potential benefits of esketamine+AD for both acute and maintenance use. LHH was favorable esketamine+AD was 3 times more likely to result in acute remission vs discontinuation due to an AE. FUNDING ACKNOWLEDGEMENTS Janssen Global Services, LLC.BACKGROUND Opioid antagonists may mitigate medication-associated weight gain and/or metabolic dysregulation. ENLIGHTEN-2 evaluated a combination of olanzapine and the opioid antagonist samidorphan (OLZ/SAM) vs olanzapine for effects on weight gain and metabolic parameters over 24 weeks in adults with stable schizophrenia. Neratinib ic50 METHODS This phase 3, double-blind study (ClinicalTrials.gov NCT02694328) enrolled adults 18-55 yo with stable schizophrenia, randomized 11 to once-daily OLZ/SAM or olanzapine. Co-primary endpoints were percent change from baseline in body weight and proportion of patients with ≥10% weight gain at week 24. Waist circumference and fasting metabolic parameters were also measured. Completers could enter a 52-week open-label safety extension. RESULTS 561 patients were randomized 550 were dosed, 538 had ≥1 post-baseline weight assessment, and 352 (64%) completed; 10.9% discontinued due to AEs. At week 24, least squares mean (SE) percent weight change from baseline was 4.21 (0.68)% with OLZ/SAM and 6.59 (0.67)% with olanzapine (difference, -2.38 [0.76]%; P=0.003). Fewer patients treated with OLZ/SAM (17.8%) had ≥10% weight gain vs olanzapine (29.8%; odds ratio=0.50; P=0.003). The change from baseline in waist circumference was significantly smaller with OLZ/SAM (P less then 0.001). Common AEs (≥10%) with OLZ/SAM and olanzapine were weight increased (24.8%, 36.2%), somnolence (21.2%, 18.1%), dry mouth (12.8%, 8.0%), and increased appetite (10.9%, 12.3%), respectively. Metabolic parameter changes were generally small and remained stable with long-term OLZ/SAM treatment. DISCUSSION OLZ/SAM treatment limited weight gain associated with olanzapine. Metabolic parameter changes were generally small, similar between groups over 24 weeks, and remained stable over an additional 52 weeks of open-label OLZ/SAM treatment. FUNDING ACKNOWLEDGEMENTS This study was funded by Alkermes, Inc.INTRODUCTION Choreaform movements provoked by opiates is an infrequent adverse event. Buprenorphine induction of chorea has not heretofore been described. Such a case is presented. METHOD Case Study A 38-year-old female presented with a decade long history of alcohol, cocaine, benzodiazepine, and heroin abuse. The patient was insufflating 1.5 grams of heroin daily. On presentation, she was actively withdrawing, scoring 17 on the Clinical Opioid Withdrawal Scale. Urine toxicology screening was positive for opiates, cocaine, and cannabinoids. Buprenorphine 4 mg sublingual was initiated. Within one hour, she observed, "My legs were moving uncontrollably as if I was a marionette." These dance-like movements were isolated to both legs and gradually resolved after discontinuation of buprenorphine most of the movements manifested in the first 8 hours, and dissipated over the next 2 days. She did have similar movements after treatment with quetiapine during a previous hospitalization, years earlier. RESULTS Abnormaliar, 2017; Bonnet, 1998). The combination of simultaneous activity of these three opioid receptors may cause chorea, since they act to modulate dopamine, glutamate, and GABA in the direct and indirect pathways within the basal ganglia (Abin, 1989; Cui, 2013; Allouche, 2014; Trifilieff, 2013). This patient's history of heroin and cocaine use may have caused supersensitization of dopamine receptors (Memo, 1981), provoking hyperkinesia. Involvement of substance-induced sensitization with concurrent kappa-opioid receptor neurotransmitter augmentation in direct and indirect pathways in the basal ganglia may have primed our patient to the development of chorea after buprenorphine administration. Further investigation for the presence of extrapyramidal movements in those undergoing buprenorphine treatment is warranted.INTRODUCTION Post-traumatic dysgeusia with conversion of the taste of eggs rotten eggs has not heretofore been described. METHOD Case Report A 60 year old right handed female 6 months prior to presentation sustained head trauma. Three days later she noted reduced taste and smell dysgeusia to eggs. Eggs tasted distorted, like rotten eggs. Raw egg whites had no smell or taste. Cooked egg whites had faint sulfur smell for 2-3 seconds and the taste of sulfur. Yolk of soft-boiled eggs, had no smell or taste. The white had no smell but an unbearable sulfur taste. Raw eggs had no smell. The yolk of hardboiled eggs had no smell and taste, the whites smelled and tasted like sulfur. Sunny side up eggs with yolk and white segregated had no smell but tasted, as they should. Sunny side up eggs with yolk and white mixed together has no smell but strong sulfur taste. Scrambled eggs had no smell but mild sulfur taste, which changed over time to a rotten egg smell and taste. With nose clips, scrambled eggs had 0/10 taste, without the nose clips the smell of sulfur was 3/10. RESULTS Olfaction Normosmia to threshold and Retronasal Smell Index 2 (abnormal) Gustatation Normogeusia to all. Mild hypogeusia to sodium chloride. MRI Multiple foci of periventricular and deep white matter demyelization. DISCUSSION Rotten egg smell maybe mediated through retro-nasal pathways, since nasal obstruction eliminated the rotten egg taste. Eggs can possibly be developed as a home device to assess chemosensory function.STUDY OBJECTIVE SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P302) evaluated the efficacy and safety of once-daily SPN-812 at doses of 200 and 400 mg compared to placebo in adolescents ages 12-17yrs with ADHD. METHOD Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=310) were randomized 111 to placebo200 mg SPN-812400 mg SPN-812. The treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population N=301; placebo=104, 200 mg=94, 400 mg=103).