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1.
JAMA Netw Open ; 4(11): e2133090, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1516696

ABSTRACT

Importance: Antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)-specifically fluoxetine hydrochloride and fluvoxamine maleate-with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size. Objective: To investigate the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs). Design, Setting, and Participants: This retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-treated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centers across the US. Exposures: Selective serotonin reuptake inhibitors and specifically (1) fluoxetine, (2) fluoxetine or fluvoxamine, and (3) other SSRIs (ie, not fluoxetine or fluvoxamine). Main Outcomes and Measures: Death. Results: A total of 3401 adult patients with COVID-19 prescribed SSRIs (2033 women [59.8%]; mean [SD] age, 63.8 [18.1] years) were identified, with 470 receiving fluoxetine only (280 women [59.6%]; mean [SD] age, 58.5 [18.1] years), 481 receiving fluoxetine or fluvoxamine (285 women [59.3%]; mean [SD] age, 58.7 [18.0] years), and 2898 receiving other SSRIs (1733 women [59.8%]; mean [SD] age, 64.7 [18.0] years) within a defined time frame. When compared with matched untreated control patients, relative risk (RR) of mortality was reduced among patients prescribed any SSRI (497 of 3401 [14.6%] vs 1130 of 6802 [16.6%]; RR, 0.92 [95% CI, 0.85-0.99]; adjusted P = .03); fluoxetine (46 of 470 [9.8%] vs 937 of 7050 [13.3%]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = .03); and fluoxetine or fluvoxamine (48 of 481 [10.0%] vs 956 of 7215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06). Conclusions and Relevance: These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.


Subject(s)
Antidepressive Agents , COVID-19/mortality , Fluoxetine , Fluvoxamine , Serotonin Uptake Inhibitors , Severity of Illness Index , Adult , Aged , Antidepressive Agents/pharmacology , COVID-19/metabolism , Citalopram/pharmacology , Cytokines/metabolism , Female , Fluoxetine/pharmacology , Fluvoxamine/pharmacology , Humans , Male , Middle Aged , Prescription Drugs , Retrospective Studies , Risk , SARS-CoV-2 , Serotonin Uptake Inhibitors/pharmacology , Sertraline , United States
2.
Biomed Pharmacother ; 144: 112291, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1466070

ABSTRACT

BACKGROUND: Oxytocin (OXT), a neuropeptide involved in mammal reproductive and prosocial behaviors, has been reported to interact with various stressor-provoked neurobiological changes, including neuroendocrine, neurotransmitter, and inflammatory processes. In view of disturbances in psychosocial relationships due to social isolation and physical distancing measures amid the COVID-19 pandemic, being one of the triggering factors for the recent rise in depression and anxiety, OXT is a potential candidate for a new antidepressant. METHODS: In this present study, we have aimed to investigate the effects of oral administration of Rosmarinus officinalis extract (RE), extracted from distillation residue of rosemary essential oil, on central OXT level in the context of other stress biomarkers and neurotransmitter levels in mice models. Tail suspension test (TST) and elevated plus maze test (EPMT) following LPS injection were employed to assess depressive- and anxiety-like behavior in mice, respectively. FINDINGS: Pretreatment with RE for seven days significantly improved behavior in TST and EPMT. Whole-genome microarray analysis reveals that RE significantly reversed TST stress-induced alterations in gene expressions related to oxytocinergic and neurotransmitter pathways and inflammatory processes. In both models, RE significantly increased central Oxt and Oxtr expressions, as well as OXT protein levels. RE also significantly attenuated stress-induced changes in serum corticosterone, brain and serum BDNF levels, and brain neurotransmitters levels in both models. INTERPRETATION: Altogether, our study is the first to report antidepressant- and anxiolytic-like activities of RE through modulating oxytocinergic system in mice brain and thus highlights the prospects of RE in the treatment of depressive disorders of psychosocial nature.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Oxytocin/metabolism , Plant Extracts/therapeutic use , Receptors, Oxytocin/metabolism , Rosmarinus , Animals , Anti-Anxiety Agents/isolation & purification , Anti-Anxiety Agents/pharmacology , Antidepressive Agents/isolation & purification , Antidepressive Agents/pharmacology , Anxiety/drug therapy , Anxiety/metabolism , Brain/drug effects , Brain/metabolism , Depression/drug therapy , Depression/metabolism , Dose-Response Relationship, Drug , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Male , Mice , Mice, Inbred ICR , Oxytocin/agonists , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Receptors, Oxytocin/agonists
3.
Nurs Stand ; 36(9): 77-81, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1369911

ABSTRACT

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.


Subject(s)
Analgesics , Anesthetics , Ketamine , Analgesics/pharmacology , Analgesics/therapeutic use , Anesthetics/pharmacology , Anesthetics/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Humans , Ketamine/pharmacology , Ketamine/therapeutic use
4.
Pharmacopsychiatry ; 54(5): 215-223, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1217715

ABSTRACT

INTRODUCTION: Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods. METHODS: WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H2DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (ser-1, ser-4, ser-7) and serotonin transporter (mod-5). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6. RESULTS: WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5. LIMITATIONS: Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings. CONCLUSION: WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression.


Subject(s)
Depression , Receptors, Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Synaptic Transmission/drug effects , Withanolides/pharmacology , Animals , Animals, Genetically Modified , Antidepressive Agents/pharmacology , COVID-19/psychology , Caenorhabditis elegans , Depression/drug therapy , Depression/metabolism , Fluoxetine/pharmacology , Humans , Longevity/drug effects , Oxidative Stress/drug effects , SARS-CoV-2
5.
Molecules ; 26(7)2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1167670

ABSTRACT

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.


Subject(s)
Antidepressive Agents/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Aging/drug effects , Aging/physiology , Animals , Antioxidants/pharmacology , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Gene Knockout Techniques , Heat-Shock Response/drug effects , Longevity/drug effects , Longevity/genetics , Longevity/physiology , Mutation , Osmotic Pressure/drug effects , Oxidative Stress/drug effects , Plant Extracts/chemistry , Reactive Oxygen Species/metabolism
6.
Int J Mol Sci ; 22(5)2021 Mar 03.
Article in English | MEDLINE | ID: covidwho-1129729

ABSTRACT

Depression coexists with epilepsy, worsening its course. Treatment of the two diseases enables the possibility of interactions between antidepressant and antiepileptic drugs. The aim of this review was to analyze such interactions in one animal seizure model-the maximal electroshock (MES) in mice. Although numerous antidepressants showed an anticonvulsant action, mianserin exhibited a proconvulsant effect against electroconvulsions. In most cases, antidepressants potentiated or remained ineffective in relation to the antielectroshock action of classical antiepileptic drugs. However, mianserin and trazodone reduced the action of valproate, phenytoin, and carbamazepine against the MES test. Antiseizure drug effects were potentiated by all groups of antidepressants independently of their mechanisms of action. Therefore, other factors, including brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) modulation, should be considered as the background for the effect of drug combinations.


Subject(s)
Anticonvulsants/pharmacology , Antidepressive Agents/pharmacology , Drug Interactions/physiology , Animals , Disease Models, Animal , Electroshock/methods , Humans , Mice
7.
Med Hypotheses ; 146: 110468, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-988863

ABSTRACT

Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials.


Subject(s)
COVID-19/drug therapy , Tramadol/pharmacology , Analgesics, Opioid/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Antidepressive Agents/pharmacology , Antioxidants/pharmacology , COVID-19/complications , COVID-19/physiopathology , Drug Repositioning , Humans , Immunologic Factors/pharmacology , Models, Biological , Pandemics , SARS-CoV-2
8.
Emerg Microbes Infect ; 9(1): 2245-2255, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-795734

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Related Coronavirus 2 (SARS-CoV-2) is a global health emergency. As only very limited therapeutic options are clinically available, there is an urgent need for the rapid development of safe, effective, and globally available pharmaceuticals that inhibit SARS-CoV-2 entry and ameliorate COVID-19 severity. In this study, we explored the use of small compounds acting on the homeostasis of the endolysosomal host-pathogen interface, to fight SARS-CoV-2 infection. We find that fluoxetine, a widely used antidepressant and a functional inhibitor of acid sphingomyelinase (FIASMA), efficiently inhibited the entry and propagation of SARS-CoV-2 in the cell culture model without cytotoxic effects and also exerted potent antiviral activity against two currently circulating influenza A virus subtypes, an effect which was also observed upon treatment with the FIASMAs amiodarone and imipramine. Mechanistically, fluoxetine induced both impaired endolysosomal acidification and the accumulation of cholesterol within the endosomes. As the FIASMA group consists of a large number of small compounds that are well-tolerated and widely used for a broad range of clinical applications, exploring these licensed pharmaceuticals may offer a variety of promising antivirals for host-directed therapy to counteract enveloped viruses, including SARS-CoV-2.


Subject(s)
Antidepressive Agents/pharmacology , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/virology , Enzyme Inhibitors/pharmacology , Fluoxetine/pharmacology , Pneumonia, Viral/virology , Betacoronavirus/physiology , COVID-19 , Cell Line , Endosomes/virology , Humans , Pandemics , SARS-CoV-2 , Sphingomyelin Phosphodiesterase/antagonists & inhibitors , Virus Replication/drug effects
9.
Med Hypotheses ; 144: 110140, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-670383

ABSTRACT

While researchers are struggling to develop a vaccine for coronavirus disease, it is important to evolve effective therapeutic strategies to save lives. The majority of coronavirus disease deaths are due to pneumonia. Mostly, stress and depression are associated with coronavirus disease infection and thus, resulting in weakening of patients' immune response and hence, more severe respiratory symptoms or even death. We propose using a class of antidepressants named selective serotonin reuptake inhibitors for their reported potential antiviral effect, modulatory effect of respiratory symptoms, antioxidant properties and immunoregulatory effects beside their main action as antidepressant. In addition, the low cost of selective serotonin reuptake inhibitors might add a benefit for coronavirus disease patients.


Subject(s)
Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Serotonin Uptake Inhibitors/pharmacology , Anticoagulants/pharmacology , Antidepressive Agents/pharmacology , Antioxidants/pharmacology , Antiviral Agents/pharmacology , Cytokines/metabolism , Depression/drug therapy , Humans , Immune System , Inflammation , Lung/drug effects , Models, Theoretical , Risk , Serotonin/metabolism , Sertraline/pharmacology , Stress, Psychological
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