A Comparison of Pediatric Mental Health Diagnoses and Selective Serotonin Reuptake Inhibitor Prescribing Before and During the COVID-19 Pandemic.

PURPOSE: To assess the rate of mental health diagnoses and selective serotonin reuptake inhibitor (SSRI) prescribing before and during the Coronavirus Disease 2019 pandemic. METHODS: We conducted a cross-sectional study at an ambulatory pediatric clinic. A prepandemic (June 2018 to June 2019) and intrapandemic (June 2020 to June 2021) cohort were reviewed. The rate of mental health visits and new SSRI prescriptions were compared. Chi-squared analyses demonstrated a variance of statistical significance. RESULTS: From 15,414 encounters (9,791 prepandemic and 5,623 intrapandemic), 397 mental health encounters were identified. 231 (4.1%) encounters occurred during the pandemic (vs. 1.7% prepandemic) and 63 (27.3%) SSRIs were prescribed (vs. 5.4% prepandemic). Mental health encounters (prevalence ratio 2.42, 95% confidence interval, 1.99-2.95, p < .001) and SSRI prescriptions (prevalence ratio 5.03, 95% confidence interval, 2.58-9.82, p < .001) were higher during the pandemic. DISCUSSION: Our findings demonstrate increased rates of SSRI prescribing and mental health diagnoses during the Coronavirus Disease 2019 pandemic, suggesting an increased incidence of these conditions. Clinicians should be prepared to manage and screen for mental health conditions.

Antidepressant use and risk of intubation or death in hospitalized patients with COVID-19: A retrospective cohort study of clinical effectiveness.

Initial controlled trials of the serotonergic antidepressant fluvoxamine showed promise for treatment of mild to moderate COVID-19 in outpatients, although more recent outpatient data have been less encouraging. Turning to studies of hospitalized patients, a retrospective cohort study by Hoertel and associates in 2021 found a markedly reduced risk of intubation or death among patients hospitalized with COVID-19 who were receiving serotonergic antidepressants at the time of admission vs. those not receiving antidepressants. In an attempt to replicate these latter findings, we performed a similarly designed study of 500 individuals hospitalized with COVID-19 in a large academic hospital system who were taking a serotonergic antidepressant at the time of admission compared with two groups (N = 573 and N = 593) not receiving an antidepressant. In analyses controlling for demographic and clinical variables, we found no significant difference in effect between the antidepressant group and either of the two comparison groups [hazard ratios (95% CI) for intubation or death 1.1 (0.83-1.5) and 1.1 (0.86-1.5); and for death alone 1.3 (0.93-1.8) and 1.1 (0.85-1.7)]. Examining the results of our study, along with those of Hoertel et al. and three additional retrospective cohort studies in inpatients published in the interim, the data permit only very limited conclusions, with the findings on the effect of serotonergic antidepressants ranging from a strongly protective effect to no effect. Although there are numerous threats to validity that might account for this wide range of findings, we could not identify any principal factor or set of factors that could clearly explain the differences.

The effect of selective serotonin and norepinephrine reuptake inhibitors on clinical outcome of COVID-19 patients: A systematic review and meta-analysis.

Background and Aim: Due to the high social and economic burden and also mortality and morbidity caused by coronavirus disease 2019 (COVID-19) in the past few years, researchers have aimed at finding solutions to suppressing the severity of infection. Recently, selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) have been investigated as an adjuvant treatment for COVID-19. The aim of the current study was to investigate the impact of SSRI/SNRIs on outcomes of COVID-19 patients. Methods: In this systematic review and meta-analysis, a comprehensive search strategy consisting of relevant words was performed by two researchers in PubMed, Scopus and EMBASE libraries. Studies reporting the effect of SSRI and/or SNRI use in COVID-19 patients' outcome were included. Hospitalization, mortality, hospitalization event, and length of hospital stay were considered as main outcomes of this study. Analysis was carried out using Comprehensive Meta-Analysis (CMA-version 2) and final data were reported as odds ratio (OR) and 95% confidence interval (CI). Results: Our search led to the final selection of 9 articles including 15,287 patients. The effect of fluvoxamine, fluoxetine, and the overall effect of SSRI/SNRI use on mortality of COVID-19 patients were investigated in 3, 2, and 7 articles, respectively. The results of our analyses showed that these medications could significantly decrease mortality of COVID-19 patients (OR and 95% [CI]: 0.595 [0.467-0.758], 0.620 [0.469-0.821], and 0.596 [0.437-0.813]). The effect of SSRI/SNRIs on hospitalization events of COVID-19 patients was not significant (OR: 0.240% and 95% CI: 0.041-1.4). Also, length of hospital stay was longer in patients who administrated SSRIs. Conclusion: According to this study's results, SSRI/SNRIs may be effective in reducing mortality of COVID-19 patients, suggesting the superiority of fluvoxamine to fluoxetine. The safety profile and affordable cost of SSRI/SNRIs for a short-term use may be other reasons to propose them as beneficial medications in preventing mortality in COVID-19.

Psychedelic science in post-COVID-19 psychiatry.

The medium- to long-term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science shows that psilocybin therapy offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder. The COMPASS Pathways (COMPASS) phase 2b double-blind trial of psilocybin therapy in antidepressant-free, treatment-resistant depression (TRD) is underway to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of psilocybin therapy to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of psilocybin therapy in conjunction with SSRIs in TRD is not yet known. An additional COMPASS study, with a centre in Dublin, will begin to address this question, with potential implications for the future delivery of psilocybin therapy. While at a relatively early stage of clinical development, and notwithstanding the immense challenges of COVID-19, psilocybin therapy has the potential to play an important therapeutic role for various psychiatric disorders in post-COVID-19 clinical psychiatry.

Difficulty in Repurposing Selective Serotonin Reuptake Inhibitors and Other Antidepressants with Functional Inhibition of Acid Sphingomyelinase in COVID-19 Infection.

The rapid spread of COVID-19 has become a health emergency causing an urgent need for drug treatments to control the outbreak, especially in more vulnerable individuals. This is reinforced by the fact that prophylactic vaccines and neutralizing monoclonal antibodies may not be fully effective against emerging variants. Despite all efforts made by the scientific community, efficient therapeutic options currently remain scarce, either in the initial, as well as in the advanced forms of the disease. From retrospective observational studies and prospective clinical trials, selective serotonin reuptake inhibitors (SSRIs), and other antidepressants with functional inhibition of acid sphingomyelinase (FIASMAs), have emerged as potential treatments of COVID-19. This has led to some prematurely optimistic points of view, promoting a large prescription of fluvoxamine in patients with COVID-19, that we think should be reasonably tempered.

Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives?

The current 2019 novel coronavirus disease (COVID-19), an emerging infectious disease, is undoubtedly the most challenging pandemic in the 21st century. A total of 92,977,768 confirmed cases of COVID-19 and 1,991,289 deaths were reported globally up to January 14, 2021. COVID-19 also affects people's mental health and quality of life. At present, there is no effective therapeutic strategy for the management of this disease. Therefore, in the absence of a specific vaccine or curative treatment, it is an urgent need to identify safe, effective and globally available drugs for reducing COVID-19 morbidity and fatalities. In this review, we focus on selective serotonin reuptake inhibitors (SSRIs: a class of antidepressant drugs with widespread availability and an optimal tolerability profile) that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials. We also summarize the existing literature on what is known about the link between serotonin (5-HT) and the immune system. From the evidence reviewed here, we propose fluoxetine as an adjuvant therapeutic agent for COVID-19 based on its known immunomodulatory, anti-inflammatory and antiviral properties. Fluoxetine may potentially reduce pro-inflammatory chemokine/cytokines levels (such as CCL-2, IL-6, and TNF-α) in COVID-19 patients. Furthermore, fluoxetine may help to attenuate neurological complications of COVID-19.

Fluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection.

Hyperinflammatory response caused by infections such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) increases organ failure, intensive care unit admission, and mortality. Cytokine storm in patients with Coronavirus Disease 2019 (COVID-19) drives this pattern of poor clinical outcomes and is dependent upon the activity of the transcription factor complex nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and its downstream target gene interleukin 6 (IL6) which interacts with IL6 receptor (IL6R) and the IL6 signal transduction protein (IL6ST or gp130) to regulate intracellular inflammatory pathways. In this study, we compare transcriptomic signatures from a variety of drug-treated or genetically suppressed (i.e. knockdown) cell lines in order to identify a mechanism by which antidepressants such as fluoxetine demonstrate non-serotonergic, anti-inflammatory effects. Our results demonstrate a critical role for IL6ST and NF-kappaB Subunit 1 (NFKB1) in fluoxetine's ability to act as a potential therapy for hyperinflammatory states such as asthma, sepsis, and COVID-19.