Use of Psychotropics in COVID-19: Another Anti-inflammatory Pathway

The emergence of the novel coronavirus SARS-CoV-2 has significantly impacted the world's population, disrupting healthcare systems around the globe and leading to human and material losses. While different vaccines have been approved in record time, there continues to be a high number of daily new cases, and patients face a wide range of presentations of the disease, from asymptomatic to potentially fatal. Therefore, the search for therapeutic agents that can aid in the management and control of the disease has become one of the main goals for researchers and clinicians. As an inflammatory disease, targets for the treatment of COVID-19 have largely involved the immune system. Inflammation has also been associated with mental health disorders, and studies have shown the potential involvement of inflammatory pathways in the pathophysiology of depression. As a consequence, the hypothesis of using antidepressants and other psychotropics for the treatment of COVID-19 has emerged. In this review, we aim to summarize the molecular pathways that could be involved as well as the emergent evidence that has been reported by studies performed since the appearance of SARS-CoV-2 in 2019. While it has been observed that there are potential therapeutic pathways for the use of antidepressants in the treatment of COVID-19, additional studies are needed to evaluate the feasibility, safety, and efficacy of psychotropics in this disease.Copyright © 2023 Bentham Science Publishers.

Use of psychotropic drugs in the elderly in France: Are we condemned to remain at high tide?

Psychotropics are widely used drugs, especially in the elderly, especially in France. This, and the risks associated to their use, logically led to concerns that resulted in numerous studies, reports, and regulatory actions intending to limit this use. This review objective was to provide an overview of psychotropic use in elderly subjects in France for antipsychotics, antidepressants, and benzodiazepines and related drugs. The narrative review performed is structured in two parts. The first reminds the initial steps of psychotropic use monitoring in the general French population. The second provides information on psychotropic use in elderly in France using the latest open data released by the French Health Insurance system and processed using the dedicated DrugSurv tool developed within the DRUGS-SAFE® and DRUGS-SAFE® programs. This was completed examining the most recent studies regarding psychotropic use in elderly in France, whether they consisted in publications or reports. At least before the COVID-19 epidemic, decreases in psychotropic prevalence of use among the elderly in France could be observed, mostly for antipsychotics or benzodiazepines (e.g. antipsychotics, 2006-2013: 10.3% decrease and benzodiazepines 2012-2020: decrease from 30.6% to 24.7% in subjects aged ≥65). Psychotropic prevalence of use remained however very high overall (e.g. antidepressants, 2013: 13% in subjects aged 65-74 and 18% in aged ≥65), exceeding that of most other countries, with a significant proportion of inappropriate use (e.g. in 30% of benzodiazepine users, all ages) carrying a clearly identified risks for uncertain benefit. Initiatives have been multiplied at the national level to reduce psychotropic overuse in the elderly. The reported prevalences demonstrate their effectiveness is obviously insufficient. This limited effectiveness is not specific to psychotropics and might reside in a failure to create strong adherence to messages and recommendations. Other levels should be considered, especially regional, for interventions coupled with pharmacoepidemiologic monitoring allowing impact assessment.

Sales trends of psychotropic drugs in the COVID-19 pandemic: A national database study in Brazil.

Background: The social restrictions among coronavirus disease 2019 (COVID-19) pandemic have posed a thoughtful risk to mental health and have implications in the use of drugs, including antidepressants, anxiolytics and other psychotropics. Objective: This study analyzed the sales data of the psychotropics prescribed in Brazil, in order to verify the change in consumption trends of these drugs during the COVID-19 pandemic. Methods: This interrupted time-series analyzed psychotropic sales data, between January 2014 and July 2021, using the National System of Controlled Products Management from The Brazilian Health Regulatory Agency. The monthly mean DDDs per 1,000 inhabitants per day of psychotropic drugs was evaluated by analysis of variance (ANOVA) followed by Dunnett Multiple Comparisons Test. The changes in monthly trends in the use of the psychotropic studied were evaluated by Joinpoint regression. Results: During the period studied, clonazepam, alprazolam, zolpidem and escitalopram were the most sold psychotropic drugs in Brazil. According to Joinpoint regression, an upward trend was observed in sales during the pandemic of pregabalin, escitalopram, lithium, desvenlafaxine, citalopram, buproprion and amitriptyline. An increase in psychotropic consumption was noted throughout the pandemic period, with the maximum consumption (2.61 DDDs) occurring in April 2021, with a downward trend in consumption that accompanied the drop in the number of deaths. Conclusions: The increase in sales, mainly of antidepressants during the COVID-19 pandemic, draws attention to issues related to the mental health of the Brazilian population and on the need for greater monitoring in the dispensing of these drugs.

Dispensing patterns of mental health medications before and during the COVID-19 pandemic in Alberta, Canada: An interrupted time series analysis.

BACKGROUND: The COVID-19 pandemic has negatively impacted the general population in all aspects of life. Estimates of mental health medication dispensing in Alberta were investigated to elucidate areas of need within mental health and pharmacy practice during the pandemic. METHODS: We employed an interrupted time series analysis using linear regression models to estimate community and outpatient medication dispensing trends of 46 medications used to treat mental health disorders. Three parameters were examined. The first was the medication dispensing slope before COVID-19. The second was the immediate effect of COVID-19 on dispensing (i.e., the difference in dispensing rate between the month before and after the first case of COVID-19) and the third was the medication dispensing slope during COVID-19. RESULTS: Dispensing rates of 61% (n = 34) of the examined medications remained similar before and during the COVID-19 pandemic. However, eight medications (i.e., amitriptyline, escitalopram, fluoxetine, paroxetine, bupropion, desvenlafaxine, venlafaxine, and oxazepam) showed an immediate and significant increase in dispensing rate following the onset of the pandemic that was sustained over the first 13-months of the pandemic. CONCLUSION: Initial increases in dispensing patterns of antidepressants may be attributed to a "stockpiling phenomenon" but the sustained higher levels of dispensing suggest an unfavorable shift in the population's mental health. Monitoring of medication dispensing patterns during COVID-19 may serve as a useful indicator of the population's mental health during the current pandemic and better prepare community pharmacists in future pandemic planning, medication dispensing strategies, and care of chronic medical conditions.

Effect of psychotropics on the risk of COVID-19 in middle-aged and older adults.

Older adults have been markedly impacted by the coronavirus disease 19 (COVID-19) pandemic, and many reports have cited concerns regarding potential psychiatric sequelae of coronavirus disease (COVID-19), but the actual effects of psychotropics on the COVID-19 are unclear. In this study, multivariate logistic regression was used to evaluate associations between the prescription of psychotropics and the risk of SARS-CoV-2 infection, and COVID-19-related death among the participants who were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) before October 18, 2021, in UK Biobank. The psychotropics included 18 types of medications. Among 168,173 participants who underwent testing for SARS-CoV-2 RNA, 30,577 (18.2%) were positive, and 14,284 (8.5%) participants used psychotropics. Among 30,577 participants who were infected with SARS-CoV-2, 1,181 (3.9%) were COVID-19-related deaths, and 2,542 (8.3%) participants used psychotropics. In multivariate logistic regression, psychotropics use was significantly associated with the risk of SARS-CoV-2 infection (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.88-0.98), and COVID-19-related death (OR, 0.78; 95% CI, 0.64-0.98). Interestingly, the use of diazepam was significantly associated with a 31% lower risk of SARS-CoV-2 infection (OR, 0.69; 95% CI, 0.53-0.88). The use of sertraline was significantly associated with a 89% lower risk of COVID-19-related death (OR, 0.11; 95% CI, 0.02-0.39). In conclusion, our findings suggested that the use of psychotropics was associated with a lower risk of SARS-CoV-2 infection and COVID-19-related deaths.

First-generation antipsychotics use and reduced risk of pneumonia—Clinical implications in SARS-CoV2 treatment: A systematic review and meta-analysis of observational studies

The use of antipsychotics (AP) has been linked to nearly 60% increase in the incidence of pneumonia. The study purposes to devise safest treatment regimens for psychiatric patients with underlying respiratory comorbidities. A systematic literature search was conducted. A total of 41 studies were evaluated, which included 33 articles for metaanalysis. The quality of retrieved articles was screened by reviewing independently. The risk of bias in each study was assessed using the Newcastle–Ottawa Scale. Inter-rater agreement calculation was performed using Rayyan QCRI. Statistical analysis was performed using R 4.0.3. The meta-analysis conducted revealed that the risk of pneumonia (OR = 1.66;95% CI = 1.64–1.68) and respiratory failure (OR = 1.79;95% CI = 1.61–2.00) were higher in psychotropic users compared to nonusers. Pneumonia risk was higher in second-generation antipsychotic users (OR = 1.12;95% CI = 1.01–1.25) compared to other antipsychotic users. However, no association was found between firstgeneration antipsychotics and pneumonia compared to other psychotropic exposure (OR = 0.93;95% CI = 0.86–0.99). Chlorpromazine, sulpiride, and aripiprazole were found to be statistically safer compared to other AP. AP should be of appropriate choice in patients with SARS-CoV-2 infection, recurrent pneumonia history or those with opportunistic infections. © 2022 Abhirami Eby et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

CHALLENGES REGARDING THE INTERACTION BETWEEN PSYCHOTROPICS AND COVID-19 CO-MEDICATION

Coronavirus disease 19 (COVID-19) pandemic is at the moment the main topic of interest regarding medical science and research. Responsible for the disease is a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accountable for over 118 million cases and a total of 2.61 million deaths worldwide (July 2020). Drug treatment for infected COVID-19 patients represents a difficult task, since there is no currently licensed specific antiviral for SARS-CoVs, the clinical approach of these patients remains the symptomatic one and also providing supportive care if needed. The clinical approach becomes more of a challenge especially if one has a co-existing psychiatric illness under psychotropic treatment. This concern is raised due to potential drug-to-drug interactions (DDIs) between antiviral agents and psychotropics, not only by common metabolic pathways regarding P450 cytocromial enzymes but also by pharmacological synergism regarding common adverse effects. Thus, we searched to identify studies published in PubMed medical database to support clinical practice in these situations and found that mostly all main psychotropics are implied in DDIs with the antivirals used to treat COVID-19 infection. Therefore, the clinical approach in treating COVID-19 patients with antiviral agents remains a challenge especially for those who have a comorbid psychiatric illness and are under treatment with psychotropics.

New-Onset Catatonia and Delirium in a COVID-Positive Patient.

Coronavirus disease (COVID-19) is a strain of coronavirus family, which was initially found in China in late 2019 and subsequently spread to rest of the world. COVID-19 has led to physical and mental health complications since its onset. In addition to the pandemic-associated social stresses, biological complications include direct viral encephalitis, autoimmune-mediated responses, medication side effects, hypoxic brain injury, and delirium, which can collectively cause varied presentations of neuropsychiatric symptoms. Neuropsychiatric complications have been reported in the acute stages of COVID-19 and post-infection period. Here we report our experience treating a patient who initially presented with a severe depressive episode and subsequently developed catatonia and delirium following hospital-acquired COVID-19 infection.

Psychotropics and COVID-19: An analysis of safety and prophylaxis.

The use of psychotropics during the COVID-19 pandemic has raised two questions, in order of importance: first, what changes should be made to pharmacological treatments prescribed to mental health patients? Secondly, are there any positive side effects of these substances against SARS-CoV-2? Our aim was to analyze usage safety of psychotropics during COVID-19; therefore, herein, we have studied: (i) the risk of symptomatic complications of COVID-19 associated with the use of these drugs, notably central nervous system activity depression, QTc interval enlargement and infectious and thromboembolic complications; (ii) the risk of mistaking the iatrogenic impact of psychotropics with COVID-19 symptoms, causing diagnostic error. Moreover, we provided a summary of the different information available today for these risks, categorized by mental health disorder, for the following: schizophrenia, bipolar disorder, anxiety disorder, ADHD, sleep disorders and suicidal risk. The matter of psychoactive substance use during the pandemic is also analyzed in this paper, and guideline websites and publications for psychotropic treatments in the context of COVID-19 are referenced during the text, so that changes on those guidelines and eventual interaction between psychotropics and COVID-19 treatment medication can be reported and studied. Finally, we also provide a literature review of the latest known antiviral properties of psychotropics against SARS-CoV-2 as complementary information.

Reviewing the physiology, pharmacology and therapeutic uses of ketamine.

Ketamine is a synthetic drug with unique properties which started to be used therapeutically in humans in the 1970s and is now widely used in all fields of nursing. Ketamine acts on the central nervous system, primarily through inhibiting N-methyl-D-aspartate receptors. However, the precise understanding of its mechanisms of action remains elusive in many respects. Ketamine is frequently used as an anaesthetic in medical and surgical procedures and as an analgesic in children and adults. It is increasingly used in mental health settings to treat depression. It has potential to be used more often in areas such as palliative care and mental health care. This article reviews the physiological and pharmacological properties of ketamine, explores its main therapeutic uses, and considers the associated implications for nursing practice.

[Challenges for psychotropics in the context of the SARS-Cov-2 pandemic]. / Enjeux de l'utilisation des psychotropes dans le cadre de la pandémie au SARS-Cov-2.

French recommendations have been proposed for psychotropics use and possible adaptations during the SARS-CoV-2 epidemic. Between uncertainties linked to the lack of data and speculations about possible benefits of psychotropics against the coronavirus, we propose here elements allowing to base the pharmacotherapeutic decisions potentially useful in Covid+ patients with psychiatric disorders.

[Informations on psychotropics and their adaptations for patients suffering from mental disorders in France during the SARS-CoV-2 epidemic]. / Informations relatives aux psychotropes et à leurs adaptations éventuelles pour les patients souffrant de troubles psychiques en France pendant l'épidémie à SARS-CoV-2.

The 2019-20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage - in case of minimal infectious signs and in a situation, which does not allow rapid control - should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.