NEI 2022 Abstracts

The proceedings contain 96 papers. The topics discussed include: practical pharmacotherapy for opioid use disorder in the age of fentanyl;can COVID-19 cause acute psychosis in pediatric patients? a case report;a survey of bullying experiences in a child and adolescent psychiatric clinic population;acute emergence of suicidal thoughts following Lemborexant initiation: an adverse reaction case report;assessing the unmet clinical need and opportunity for digital therapeutic intervention in schizophrenia: perspective from people with schizophrenia;rapid antidepressant effects and MADRS item improvements with AXS-05 (DEXTROMETHORPHAN-BUPROPION), an oral NMDA receptor antagonist in major depressive disorder: results from two randomized double-blind, controlled trials;targeting lncRNA NEAT1 impedes Alzheimers disease progression via MicroRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways;and impact of AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA receptor antagonist, on Anhedonic symptoms in major depressive disorder.

Self-medication Practices for COVID-19 Prevention: A Study among Medical Students in Yogyakarta, Indonesia

The corona virus disease 2019 (COVID-19) pandemic has increased the interest in self-care strategies, including self-medication. Medical students, as future health practitioners, learn more about medications than other students. This study aimed to describe self-medication practices for preventing COVID-19 among medical students at Universitas Islam Indonesia. This observational study used a cross-sectional design and was undertaken in November- December 2020. The study sample included 336 undergraduate medical students determined using a consecutive sampling technique based on inclusion and exclusion criteria. Data were collected using an online questionnaire about self-medication practices in the preceding 3 months. Among a total of 336 students, 137 (41%) reported using self-medication intending to prevent COVID-19, and 126 (92%) of these 137 took preventive supplements, mainly vitamins C, D, and E, and omega-3. Seven students reported the use of zinc, mainly in combination with other vitamins. Students who practiced self-medication lived closer to people confirmed with COVID-19, washed their hands more often, and desinfected their belongings more frequently than their counterparts (p<0.05). The mean duration for consuming vitamins was 11-16 days. Forty students (29%) used herbal medicine to prevent COVID-19;ginger, turmeric, honey, black seed, cutcherry, and Curcuma were the most often consumed herbal remedies. Fourteen students (10%) reported taking over-the-counter medications to relieve symptoms related to COVID-19, including antipyretic, analgesic, antiseptic, antihistamine, decongestant, antitussive, and expectorant medications. Most respondents (82%) purchased their medications at pharmacies, and 11 (9%) obtained them from online shops. These findings show the high rate of self-medication using vitamins and herbal remedies for COVID-19 prevention among university medical students. Further studies are needed to explore students' knowledge about the risks of self-medication including the use of herbal medicines.Copyright © 2022 Marmara University Press.

Pharmacovigilance practices in South Asian Association for Regional Cooperation countries: the need for collaboration

Objectives: One-fifth of the world's population lives in eight countries that constitute the South Asian Association for Regional Cooperation (SAARC). There is very little coordination among SAARC countries regarding the harmonization of pharmaceutical regulations and medicines safety. Pakistan, India and Bangladesh have experienced medicine-related tragedies where many patients have died. This study aims to examine current pharmacovigilance activity in the SAARC region to improve pharmacovigilance practices and to make recommendations for building a platform for collaboration to improve the safety monitoring of medicines in the region. The current review utilized secondary data. We reviewed the official websites of all SAARC countries' national regulatory authorities for pharmacovigilance-related information. A data set with eleven pharmacovigilance indicators were gathered and synthesized. Key Findings: All eight SAARC member countries have pharmacovigilance systems with full membership in the WHO Program for International Drug Monitoring. Out of eleven pharmacovigilance indicators, India met ten;Pakistan, Bangladesh and Bhutan nine;Maldives and Afghanistan seven;Nepal and Sri Lanka five. The SAARC countries do not have a harmonized pharmacovigilance system or centralized database. Due to positioning in different WHO regions, it is proposed to create a consortium on medicine safety among SAARC countries like other regional organizations of the world to strengthen the pharmacovigilance systems and harmonize the pharmacovigilance practices among member countries. Summary: To improve the quality of medicines and to strengthen regional medicine safety, the SAARC secretariat should consider forming a technical group of all member countries' regulatory authorities.Copyright © 2022 The Author(s). Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved.

Two Cases of Dextromethorphan Overdose Reversed by Naloxone.

We present two rare cases highlighting the rare toxicological manifestation of dextromethorphan (DXM). The DXM toxicity profile is predominantly hallucinations, agitation, irritability with seizures, and coma in severe overdose. The cases that follow are unique in the sense that both patients had features of opioid toxidrome, rarely manifested in DXM abuse. A young male and female in their mid-20s and early 30s, respectively, were brought to the emergency room for their excessive somnolence; both had reduced respiratory rate, bilaterally small pupils (sluggish reactive to light), and the rest of their examination findings were unremarkable. Primary stabilization in the form of noninvasive ventilation (NIV) trial and subsequent rapid sequence intubation (RSI) for persistent respiratory depression. Followed by the exhaustive exclusion of differentials, opioid-like toxidrome was treated with naloxone, and both patients made a good recovery and were discharged home in good health. The emergency physician should be prepared for the rare toxicological manifestations of commonly available over-the-counter medications among the youth. These case reports highlight the role of naloxone in DXM toxicity reversal.

Effectiveness of antitussives, anticholinergics, and honey versus usual care in adults with uncomplicated acute bronchitis: a multiarm randomized clinical trial.

BACKGROUND: Despite the frequent use of symptomatic therapies in cough, evidence of their benefits is lacking. OBJECTIVE: We compared the effectiveness of 3 symptomatic therapies and usual care in acute bronchitis. METHODS: Multicenter, pragmatic, multiarm parallel group, open randomized trial in primary care (ClinicalTrials.gov, Identifier: NCT03738917) was conducted in Catalonia. Patients ≥18 with uncomplicated acute bronchitis, with cough<3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough (7-point Likert scale), were randomized to usual care, dextromethorphan 15 mg t.i.d., ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or 30 mg of honey t.i.d., all taken for up to 14 days. The main outcome measure was the number of days with moderate-to-severe cough. A symptom diary was given. A second visit was scheduled at days 2-3 for assessing evolution, with 2 more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance, and complications. RESULTS: We failed to achieve the sample size scheduled due to the COVID-19 pandemic. We finally recruited 194 patients. The median number of days with moderate-to-severe cough (score ≥ 3) in the usual care arm was 5 (interquartile range [IQR], 4, 8.75), 5 in the ipratropium bromide arm (IQR, 3, 8), 5 in the dextromethorphan arm (IQR, 4, 9.75), and 6 in the honey arm (IQR, 3.5, 7). The same results were obtained in the Kaplan-Meier survival analysis for the median survival time of each arm with the usual care as the reference group. CONCLUSION: The symptomatic treatment evaluated has shown to be ineffective against cough.

Cough is the most frequent symptom reported by patients with lower respiratory tract infections. Despite being a defense mechanism, cough is unpleasant and negatively affects sleep and overall well-being. Accordingly, many patients with acute cough seek medical help to mitigate symptoms and reduce their duration despite the typically self-limiting nature of the condition. In this randomized clinical trial, we explored the benefit of 3 common symptomatic treatments recommended in some guidelines for relieving this symptom during the course of uncomplicated acute bronchitis, a cough suppressant, an inhaler, and honey intake. Although the total number of patients initially expected could not be achieved due to the disruption caused by the COVID-19 pandemic, the results of our study demonstrate a lack of efficacy of these products as the number of days of severe-to-moderate cough was similar in the 3 arms and comparable to the group of patients allocated to usual care.

Misuse of prescription and over-the-counter drugs to obtain illicit highs: how pharmacists can prevent abuse

There have been increasing reports of misuse of a range of prescription and over-the-counter (OTC) drugs for recreational purposes. The use of psychoactive pharmaceuticals and 'pharming' are new, widespread phenomena involving the non-medical use of prescription and OTC drugs, which are recreationally used to achieve psychoactive effects either on their own or in combination with other substances. This article provides an overview of the topic, focusing on a range of medicines (e.g. prescription medicines such as quetiapine, gabapentinoids, Z-drugs, bupropion, venlafaxine and over-the-counter medicines such as loperamide, dextromethorphan, benzydamine, promethazine, chlorphenamine, diphenhydramine and hyoscine butylbromide) that have emerged as misused and diverted, or are already described through the literature, as well as recorded by drug users' online websites reporting new trends and experimentations of drug abuse. This rapidly changing drug scenario represents a challenge for pharmacy, psychiatry, public health and drug control policies. Moreover, possibly resulting from the COVID-19 pandemic, drug use habits and availability have changed, causing a shift in behaviours relating to both prescription and OTC medicines. Healthcare professionals should be aware of potential prescription drugs diversion, recognise misuse cases, consider the possibility of polydrug misuse, and prevent it where possible. Pharmacists can prevent and reduce drug abuse, and should be involved in evidence-based actions to detect, understand and prevent drug diversion activities and the adverse effects of drug misuse. Copyright © 2020 Pharmaceutical Press. All rights reserved.

COVID-19 Amyotrophic Lateral Sclerosis(ALS) Registry NCT04559009

Objective: To capture the impact of COVID-19 on ALS by creating a patient-facing observational registry. Background: This observational registry is aimed to assess the impact of COVID-19 on ALS disease trajectory to help guide future directions of care, especially the role of COVID-19 on respiratory compromise and corroborate other demographic features. Design/Methods: ALS patients, and/or caregivers invited to report demographics, COVID-19 diagnosis and treatment details via a secure registry questionnaire through a REDCap Database. Patients are recruited by open announcement/email invitations via Center for Disease Control (CDC), National ALS Registry, ALS Association (national), ALS patient support organizations, Letter to MDA, ALSA and Northeast ALS Consortium Centers as well as ClinicalTrials.gov. Results: Registered ALS patients with documented COVID-19 infection [14] completed the survey to date: 9 - males;5- females. All participants were Caucasian. Mean BMI was 26.31. 62.5% had no history of tobacco use. Concomitant ALS medications included: riluzole - 60%, edaravone -13.3%, dextromethorphan/quinidine -13.3%, no medications - 33.3 %. COVID-19 infection interrupted clinical trial participation - 20.0%. COVID-19 infection was treated at home in 73.3% while 26.7% were hospitalized. 13.3% were on NIV while 86.7% were not. Concomitant COVID-19 medications included Remdesivir - 14.3%, Azithromycin - 21.4%, Corticosteroids 28.6%, no COVID-19 directed therapies - 57.1%. All of the 26.7 % hospitalized patients were discharged home. Pre COVID-19 total ALSFRS R scores (28 to 47) changed minimally during COVID-19 (27 to 47). Conclusions: In this COVID 19 ALS Registry participants to date, there were no COVID-19 related deaths in all Caucasian, predominately riluzole treated cohort and all have returned to home care with no significant change in ALSFRS R Scores post COVID. Further recruitment is ongoing to enrich COVID-19 infected ALS patients on wider range of ALS modifying therapies and expanding spectrum of COVID-19 modifying therapies from different periods of this ongoing pandemic to define in more detail their experience.

Acute psychosis and serotonin syndrome in the setting of "Triple-C" overdose: a case report.

BACKGROUND: Over-the-counter medication overdose is a difficult diagnostic challenge for many physicians as common drug screening assays cannot detect these substances. We present a case of acute psychosis, serotonin syndrome, and anticholinergic overdose-like properties in the setting of Coricidin HBP Cough & Cold tablets, known by their street name Triple-C. This is the first case report we are aware of involving a patient presenting with these symptoms and requiring critical-care-level support. CASE PRESENTATION: A 31-year-old African American female with a past medical history of anxiety, childhood asthma, previous methamphetamine abuse, and coronavirus disease 2019 infection in August 2020 was brought to the emergency department by the local police department with altered mental status. Initial blood work, including extended drug screens, were unremarkable for a definitive diagnosis. This patient required critical-care-level support and high sedation because of her symptoms. Collateral history revealed the patient regularly consumed Triple-C daily for the 6 weeks prior to admission. A trial off sedation was attempted after 24 hours with no complications. The patient admitted to regular Triple-C consumption and auditory hallucinations since adolescence. She was discharged safely after 48 hours back into the community. She was lost to follow-up with psychiatry and internal medicine; however, she was evaluated in the emergency room 1 month later with a similar psychiatric presentation. CONCLUSION: Overdose of Triple-C should be kept in the differential diagnosis of patients presenting with a triad of psychosis, serotonin syndrome, and anticholinergic overdose, in the setting of unknown substance ingestion.

In silico screening predicts common cold drug Dextromethorphan along with Prednisolone and Dexamethasone can be effective against novel Coronavirus disease (COVID-19).

The ongoing outbreak of Coronavirus disease 2019 (COVID-19) is a matter of great concern. Although the mortality rate caused by this virus is less than that of SARS and MERS, it is showing higher efficacy in terms of human-to-human transmission. Several strategies have been taken by scientists and researchers worldwide to combat this virus. Numerous phytochemicals and synthesized chemicals are under incessant inspection to obtain a potent anti-covid drug. Since, till now no precise therapy is available for covid patients, researchers are trying to categorize all possible anti-covid substances. Repurposing of drugs and combined drug therapy are becoming popular in treating such viral diseases. In this study, we are proposing the repurposing of three chemicals-Dextromethorphan, Prednisolone and Dexamethasone as anti-covid agents. We have used the tertiary structure of Coronavirus main protease (Mpro) with PDB ID 6LU7 as the target protein in this analysis. Molecular docking and dynamics study further revealed their synergistic effect against the COVID-19 protease protein.Communicated by Ramaswamy H. Sarma.

Insights into the biased activity of dextromethorphan and haloperidol towards SARS-CoV-2 NSP6: in silico binding mechanistic analysis.

The outbreak of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus continually led to infect a large population worldwide. SARS-CoV-2 utilizes its NSP6 and Orf9c proteins to interact with sigma receptors that are implicated in lipid remodeling and ER stress response, to infect cells. The drugs targeting the sigma receptors, sigma-1 and sigma-2, have emerged as effective candidates to reduce viral infectivity, and some of them are in clinical trials against COVID-19. The antipsychotic drug, haloperidol, exerts remarkable antiviral activity, but, at the same time, the sigma-1 benzomorphan agonist, dextromethorphan, showed pro-viral activity. To explore the potential mechanisms of biased binding and activity of the two drugs, haloperidol and dextromethorphan towards NSP6, we herein utilized molecular docking-based molecular dynamics simulation studies. Our extensive analysis of the protein-drug interactions, structural and conformational dynamics, residual frustrations, and molecular switches of NSP6-drug complexes indicates that dextromethorphan binding leads to structural destabilization and increase in conformational dynamics and energetic frustrations. On the other hand, the strong binding of haloperidol leads to minimal structural and dynamical perturbations to NSP6. Thus, the structural insights of stronger binding affinity and favorable molecular interactions of haloperidol towards viral NSP6 suggests that haloperidol can be potentially explored as a candidate drug against COVID-19. KEY MESSAGES: •Inhibitors of sigma receptors are considered as potent drugs against COVID-19. •Antipsychotic drug, haloperidol, binds strongly to NSP6 and induces the minimal changes in structure and dynamics of NSP6. •Dextromethorphan, agonist of sigma receptors, binding leads to overall destabilization of NSP6. •These two drugs bind with NSP6 differently and also induce differences in the structural and conformational changes that explain their different mechanisms of action. •Haloperidol can be explored as a candidate drug against COVID-19.