1.Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder
Brian MCCARTHY ; Hannah BUNN ; Morgan SANTALUCIA ; Charlotte WILMOUTH ; Andrew MUZYK ; Colin M. SMITH
Clinical Psychopharmacology and Neuroscience 2023;21(4):609-616
Depression is a significant cause of morbidity and mortality globally. Although various pharmacologic options exist for depression, treatments are limited by delayed or incomplete therapeutic response, low rates of remission, and adverse effects necessitating effective, fast-acting, and better tolerated alternatives. The purpose of this review is to describe the safety and efficacy of dextromethorphan-bupropion (Auvelity), a Food and Drug Administration approved treatment for major depressive disorder in adults. Dextromethorphan modulates glutamate signaling through uncompetitive antagonism of N-methyl-D-aspartate receptors and sigma-1 agonism, while bupropion increases the bioavailability of dextromethorphan by CYP2D6 inhibition. In a phase 3 trial with dextromethorphan-bupropion 45−105 mg for patients with major depressive disorder saw significant reductions in their Montgomery–Åsberg Depression Rating Scale total scores compared to placebo. A phase 2 trial comparing dextromethorphan-bupropion 45−105 mg to bupropion monotherapy led to significant reduction in Montgomery-Åsberg Depression Rating Scale score. Changes in Montgomery–Åsberg Depression Rating Scale with dextromethorphan-bupropion were seen within two weeks in both clinical trials. Remission and response rates were significantly higher with dextromethorphan-bupropion in both studies. The medication was well-tolerated in both trials, with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with dextromethorphan-bupropion saw large reductions in Montgomery–Åsberg Depression Rating Scale scores that were maintained through 12 and 15 months of treatment. In both long-term studies, remission rates approached 70%, while response rates were greater than 80%. These data suggest that dextromethorphan-bupropion is an effective, fast-acting, and well tolerated option for depression treatment and produced remission in a large percentage of patients.
2.Diagnosing ectopic pregnancy in the emergency setting.
Robert LEE ; Carolyn DUPUIS ; Byron CHEN ; Andrew SMITH ; Young H KIM
Ultrasonography 2018;37(1):78-87
Ectopic pregnancy is the implantation of a fertilized egg outside the uterine endometrial cavity. For women presenting to the emergency department with abdominal pain and/or vaginal bleeding, ectopic pregnancy is an important diagnostic consideration. The diagnosis is made based on laboratory values and ultrasound imaging findings. The ultrasound appearance of both normal early pregnancy and ectopic pregnancy are variable and often subtle, presenting diagnostic challenges for radiologists. This pictorial essay describes and illustrates the sonographic findings of ectopic pregnancy and reviews the differential diagnoses that can mimic ectopic pregnancy on ultrasound. With the possibility of medical management, the value of early detection and prompt initiation of treatment has increased in improving clinical outcomes and preventing the complications of ectopic pregnancy.
Abdominal Pain
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Diagnosis
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Diagnosis, Differential
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Emergencies*
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Emergency Service, Hospital
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Female
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Humans
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Methotrexate
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Pregnancy
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Pregnancy, Ectopic*
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Ultrasonography
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Uterine Hemorrhage
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Zygote
3.Sublingual Dexmedetomidine for the Treatment of Agitation in Patients with Schizophrenia and Bipolar Disorder
Colin M. SMITH ; Morgan SANTALUCIA ; Hannah BUNN ; Andrew MUZYK
Clinical Psychopharmacology and Neuroscience 2023;21(2):215-221
Acute agitation is common amongst individuals with bipolar disorder and schizophrenia and represents a medical emergency. Commonly used medications for agitation, such as benzodiazepines and antipsychotics, are often delivered intramuscularly and may cause adverse effects. Non-invasive, effective, and safe alternative treatment options are needed.The purpose of this review article is to describe the efficacy and safety of sublingual formulation of dexmedetomidine (Igalmi), a selective α2-adrenergic receptor agonist, U.S. Food and Drug Administration approved for the treatment of acute agitation in adults with schizophrenia or bipolar I and II disorder. In two phase 3 trials, two dose strengths of sublingual dexmedetomidine 180 μg and 120 μg were safe and effective in managing acute agitation in patients with bipolar disorder or schizophrenia. Both doses significantly reduced Positive and Negative Syndrome Scale-Exited Component scores two hours after receiving a single dose as compared to placebo, indicating a substantial improvement in agitation. The beneficial effects of sublingual dexmedetomidine were achieved without serious adverse events with the most common side effect being mild somnolence. The clinical trial data suggest that sublingual dexmedetomidine represents a safe and effective treatment option in the armamentarium for acute agitation for people with schizophrenia or bipolar disorder.
4.Increased proportion of alcohol-related trauma in a South London major trauma centre during lockdown: A cohort study.
Oliver S BROWN ; Toby O SMITH ; Andrew J GAUKROGER ; Prodromos TSINASLANIDIS ; Caroline B HING
Chinese Journal of Traumatology 2022;25(5):277-282
PURPOSE:
Alcohol has been associated with 10%-35% trauma admissions and 40% trauma-related deaths globally. In response to the COVID-19 pandemic, the United Kingdom entered a state of "lockdown" on March 23, 2020. Restrictions were most significantly eased on June 1, 2020, when shops and schools re-opened. The purpose of this study was to quantify the effect of lockdown on alcohol-related trauma admissions.
METHODS:
All adult patients admitted as "trauma calls" to a London major trauma centre during April 2018 and April 2019 (pre-lockdown, n = 316), and 1st April-31st May 2020 (lockdown, n = 191) had electronic patient records analysed retrospectively. Patients' blood alcohol level and records of intoxication were used to identify alcohol-related trauma. Trauma admissions from pre-lockdown and lockdown cohorts were compared using multiple regression analyses.
RESULTS:
Alcohol-related trauma was present in a significantly higher proportion of adult trauma calls during lockdown (lockdown 60/191 (31.4%), vs. pre-lockdown 62/316 (19.6%); (odds ratio (OR): 0.83, 95% CI: 0.38-1.28, p < 0.001). Lockdown was also associated with increased weekend admissions of trauma (lockdown 125/191 weekend (65.5%) vs. pre-lockdown 179/316 (56.7%); OR: 0.40, 95% CI: 0.79 to -0.02, p = 0.041). No significant difference existed in the age, gender, or mechanism between pre-lockdown and lockdown cohorts (p > 0.05).
CONCLUSIONS
The United Kingdom lockdown was independently associated with an increased proportion of alcohol-related trauma. Trauma admissions were increased during the weekend when staffing levels are reduced. With the possibility of further global "waves" of COVID-19, the long-term repercussions of dangerous alcohol-related behaviour to public health must be addressed.
Adult
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COVID-19/epidemiology*
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Cohort Studies
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Communicable Disease Control
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Humans
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London/epidemiology*
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Pandemics
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Retrospective Studies
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Trauma Centers