Tag: antidepressants

SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression

Abstract:

Background Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.

Methods In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and pre-existing major depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use at the time of COVID-19 infection and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before COVID-19 infection and not ending before COVID-19 infection. To minimize bias, we estimated the causal associations of interest using a nonparametric approach, targeted maximum likelihood estimation, to aggressively adjust for high-dimensional covariates.

Results We analyzed a sample (n = 506,903) of patients with a diagnosis of major depressive disorder before COVID-19 diagnosis, where 124,928 (25%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.90, 95% CI (0.86, 0.94)).

Conclusion These findings suggest that SSRI use during COVID-19 infection may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

Source: Zachary Butzin-Dozier, Yunwen Ji, Sarang Deshpande, Eric Hurwitz, Jeremy Coyle, Junming (Seraphina) Shi, Andrew Mertens, Mark J. van der Laan, John M. Colford Jr., Rena C. Patel, Alan E. Hubbard, the National COVID Cohort Collaborative (N3C) Consortium. SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression. medRxiv 2024.02.05.24302352; doi: https://doi.org/10.1101/2024.02.05.24302352 https://www.medrxiv.org/content/10.1101/2024.02.05.24302352v1.full-text (Full text) 

Low-Dose Naltrexone Improves post-COVID-19 condition Symptoms

Abstract:

Purpose: Treatments for myalgic encephalomyelitis and chronic fatigue syndrome can be adapted for post-COVID-19 condition. Our aim was to compare treatments in patients from our post-COVID-19 clinic.

Methods: We conducted a retrospective cohort study and included consecutive patients enrolled in our post-COVID-19 clinic. We included patients who received low-dose naltrexone, amitriptyline, duloxetine, and physical therapy, and evaluated improvements in fatigue, pain, dyspnea, and brain fog recorded in the electronic health record. We calculated the adjusted relative hazard of improvement using Cox proportional models. We adjusted for demographic characteristics, comorbidities, and prior COVID-19 hospitalization.

Findings: We included the first 108 patients with post-COVID-19 enrolled in the clinic. Most of the patients received amitriptyline. The relative hazard of improvement for those taking low-dose naltrexone was 5.04 (95% CI, 1.22-20.77; P = 0.02) compared with physical therapy alone. Both fatigue and pain were improved in patients taking low-dose naltrexone; only fatigue was improved in patients taking amitriptyline.

Implications: Post-COVID-19 condition symptoms may improve in patients taking medications adapted from myalgic encephalomyelitis and chronic fatigue syndrome. Randomized controlled trials should evaluate these medications and translational studies should further evaluate their mechanisms of action.

Source: Tamariz L, Bast E, Klimas N, Palacio A. Low-Dose Naltrexone Improves post-COVID-19 condition Symptoms. Clin Ther. 2024 Jan 23:S0149-2918(24)00003-1. doi: 10.1016/j.clinthera.2023.12.009. Epub ahead of print. PMID: 38267326. https://pubmed.ncbi.nlm.nih.gov/38267326/

Treatment of 95 post-Covid patients with SSRIs

Abstract:

After Covid-19 infection, 12.5% develops post-Covid-syndrome (PCS). Symptoms indicate numerous affected organ systems. After a year, chronic fatigue, dysautonomia and neurological and neuropsychiatric complaints predominate. In this study, 95 PCS patients were treated with selective serotonin reuptake inhibitors (SSRIs). This study used an exploratory questionnaire and found that two-thirds of patients had a reasonably good to strong response on SSRIs, over a quarter of patients had moderate response, while 10% reported no response.

Overall, patients experienced substantial improved well-being. Brainfog and sensory overload decreased most, followed by chronic fatigue and dysautonomia. Outcomes were measured with three different measures that correlated strongly with each other. The response to SSRIs in PCS conditions was explained by seven possible neurobiological mechanisms based on recent literature on PCS integrated with already existing knowledge.

Important for understanding these mechanisms is the underlying biochemical interaction between various neurotransmitter systems and parts of the immune system, and their dysregulation in PCS. The main link appears to be with the metabolic kynurenine pathway (KP) which interacts extensively with the immune system. The KP uses the same precursor as serotonin: tryptophan. The KP is overactive in PCS which maintains inflammation and which causes a lack of tryptophan. Finally, potential avenues for future research to advance this line of clinical research are discussed.

Source: Rus CP, de Vries BEK, de Vries IEJ, Nutma I, Kooij JJS. Treatment of 95 post-Covid patients with SSRIs. Sci Rep. 2023 Nov 2;13(1):18599. doi: 10.1038/s41598-023-45072-9. PMID: 37919310; PMCID: PMC10622561. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622561/ (Full text)

Long Covid & Antidepressants

Abstract:

Three years into this historic pandemic, the scientific and healthcare communities continue to learn agreat deal regarding COVID-19, the disease that is produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most urgent and immediate focus has been on vaccine development for diseaseprevention/mitigation and on identification of effective therapeutic interventions for acute phase of illness. However, attention is increasingly being placed on formulating treatment strategies for individuals who arepost-COVID-19 and experiencing a syndrome of persistent cognitive, somatic and behavioral symptoms that is being referred to as long COVID.

In addition to identifying novel compounds that may improve outcome ineither acute or residual COVID-19, an alternate and parallel strategy is to repurpose or reposition drugs which have been approved for other conditions and subsequently assess their safety and efficacy when applied toCOVID-19. In this light, antidepressant medications, particularly serotonin reuptake inhibitors, have garnered attention amidst evidence supporting their anti-inflammatory and anti-viral properties. Results from several preliminary studies suggest that early administration of antidepressants may prevent clinical deterioration and even death in patients with acute COVID-19.

In this article, we present purported anti-inflammatory mechanisms of the antidepressants, review results from studies that have appeared in the literature to date regarding antidepressants and acute COVID-19, and discuss the possible utility of antidepressants as a potential therapeutic resource for long COVID.

Source: Rivas-Vázquez R, Carrazana EJ, Blais MA, Rey GJ, Rivas-Vázquez E. Long Covid & Antidepressants. Med Discoveries. 2023; 2(3): 1023.  https://meddiscoveries.org/pdf/1023.pdf (Full text)

Treatment and outcomes of 95 post-Covid patients with an antidepressant and neurobiological explanations

Abstract:

After Covid-19 infection, 12.5% develop a post-Covid-syndrome. Symptoms affect numerous organ systems, but after one year they are mainly neurological and neuropsychiatric in nature. There is evidence that treatment with selective serotonin reuptake inhibitors (SSRIs) during Covid-19 infection decreases the likelihood of a post-Covid condition, but there is no known research on treating post-Covid syndrome itself with SSRIs.

This study used an exploratory questionnaire and found that 63,4% of 95 post-Covid syndrome patients reported a reasonably good to strong response to an SSRI. Outcomes were measured with three different measures that correlated strongly with each other. Brainfog and sensory overload decreased the most. Patients experienced improved well-being. The response to SSRIs in post-Covid conditions was explained by seven possible neurobiological mechanisms as reported in the recent literature. The promising results of this study should be followed by a randomized controlled trial.

Source: Rus CC, de Vries B, Vries IE, Nutma I, Kooij JJS. Treatment and outcomes of 95 post-Covid patients with an antidepressant and neurobiological explanations. Research Square; 2023. DOI: 10.21203/rs.3.rs-3153645/v1. https://assets.researchsquare.com/files/rs-3153645/v1/ffdd7433-9013-41d5-9f16-154074f3a204.pdf (Full text)

Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan

Abstract:

Objective: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan.

Methods: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls.

Results: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04-1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59-2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09-1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs.

A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women.

Conclusion: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.

Source: Chen C, Yip HT, Leong KH, Yao WC, Hung CL, Su CH, Kuo CF, Tsai SY. Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan. J Transl Med. 2023 Feb 8;21(1):98. doi: 10.1186/s12967-023-03886-1. PMID: 36755267; PMCID: PMC9907887. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907887/ (Full text)

Long COVID: Is There a Role for Antidepressants?

Abstract:

Two years into this historic pandemic, the scientific and healthcare communities continue to learn a great deal regarding COVID-19. The most urgent and immediate focus has been on vaccine development for disease prevention/mitigation and on identification of effective therapeutic interventions for acute phase of illness. However, attention is increasingly being placed on formulating treatment strategies for individuals who are post-COVID-19 and experiencing a syndrome of persistent symptoms that is being referred to as long COVID.

One strategy is to repurpose drugs which have been approved for other conditions and subsequently assess their safety and efficacy when applied to COVID-19. In this light, antidepressant medications have garnered attention amidst evidence supporting anti-inflammatory and anti-viral properties.

In this article, we present purported anti-inflammatory mechanisms of antidepressants, review studies appearing in the literature to date regarding antidepressants and acute COVID-19, and discuss the utility of antidepressants as a potential therapeutic resource for long COVID.

Source: Rivas-Vázquez R, Carrazana EJ, Blais MA, Rey GJ, RivasVázquez E, Quintana AA. Long COVID: Is There a Role for Antidepressants? Neurol Curr Res. 2022;2(3):1019. https://www.medtextpublications.com/open-access/long-covid-is-there-a-role-for-antidepressants-1249.pdf (Full text)

Challenges of memory enhancers

Abstract:

40 per cent of people over the age of 65 experience some form of memory loss, called as the age related memory impairment. This might be due to hormone and proteins (Growth factors) which repair the brain cells decline with age. Certain conditions such as age, stress, disease and excessive emotional response may lead to loss of memory, loss of learning ability and altered mood and behaviour. These conditions may be treated by using nootropic agents which can help to improve learning abilities and memory.

Source: Chaudhry, Sunil. Challenges of memory enhancers. Annals of Geriatric Education and Medical Sciences; 2020/08/22. https://www.agems.in/article-details/11990 (Full text)

Treatments of chronic fatigue syndrome and its debilitating comorbidities: a 12-year population-based study

Abstract:

Background: This study aims to provide 12-year nationwide epidemiology data to investigate the epidemiology and comorbidities of and therapeutic options for chronic fatigue syndrome (CFS) by analyzing the National Health Insurance Research Database.

Methods: 6306 patients identified as having CFS during the 2000-2012 period and 6306 controls (with similar distributions of age and sex) were analyzed.

Result: The patients with CFS were predominantly female and aged 35-64 years in Taiwan and presented a higher proportion of depression, anxiety disorder, insomnia, Crohn’s disease, ulcerative colitis, renal disease, type 2 diabetes, gout, dyslipidemia, rheumatoid arthritis, Sjogren syndrome, and herpes zoster. The use of selective serotonin receptor inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), Serotonin antagonist and reuptake inhibitors (SARIs), Tricyclic antidepressants (TCAs), benzodiazepine (BZD), Norepinephrine-dopamine reuptake inhibitors (NDRIs), muscle relaxants, analgesic drugs, psychotherapies, and exercise therapies was prescribed significantly more frequently in the CFS cohort than in the control group.

Conclusion: This large national study shared the mainstream therapies of CFS in Taiwan, we noticed these treatments reported effective to relieve symptoms in previous studies. Furthermore, our findings indicate that clinicians should have a heightened awareness of the comorbidities of CFS, especially in psychiatric problems.

Source: Leong KH, Yip HT, Kuo CF, Tsai SY. Treatments of chronic fatigue syndrome and its debilitating comorbidities: a 12-year population-based study. J Transl Med. 2022 Jun 11;20(1):268. doi: 10.1186/s12967-022-03461-0. PMID: 35690765. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03461-0  (Full study)

Comments to “Fluvoxamine and long COVID-19: a new role for sigma-1 receptor (S1R) agonists” by Khani and Entezari-Maleki

To the Editor:

The coronavirus disease 2019 (COVID-19) pandemic causes short-term and long-term health problems in survivors after infection of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2). A recent systematic review using 57 studies with 250,351 survivors of COVID-19 shows that the median proportion of COVID-19 survivors experiencing at least 1 PASC (post-acute sequelae of COVID-19) was 54% at 1 month (short-term), 55% at 2–5 months (intermediate-term), and 54% at 6 or more months (long-term) [1]. The most common sequelae involved neurologic symptoms (i.e., headaches, memory deficits, difficulty concentrating, cognitive impairment), psychiatric symptoms (i.e., depression, anxiety, sleep disorders), pulmonary abnormalities (i.e., dyspnea, cough, increased oxygen requirement, pulmonary diffusion abnormalities, chest imaging abnormalities), and functional mobility impairment (i.e., impairment in general functioning, mobility decline, reduced exercise tolerance). However, there are no therapeutic drugs for long-term symptoms in survivors of COVID-19.

The precise mechanisms underlying SARS-CoV-2 induced long-term detrimental effects remain unclear. Infection of SARS-CoV-2 can damage endothelial cells leading to inflammation, thrombi and brain damage. SARS-CoV-2-associated systemic inflammation leads to decreased monoamines and neurotrophic factors, and microglial activation in the brain, resulting in long-term neurological and psychiatric symptoms in COVID-19 survivors [2]. A retrospective study of Wuhan University (Wuhan, China) reported that patients with Epstein-Barr virus (EBV)/SARS-CoV-2 coinfection have about 3-fold risk of having a fever symptom than patients with SARS-CoV-2 infection alone, and that levels of C-reactive protein and aspartate aminotransferase in patients with EBV/SARS-CoV-2 coinfection were higher than those in patients with SARS-CoV-2 infection alone [3]. This report suggests that EBV reactivation may be associated with the severity of clinical symptoms after SARS-CoV-2 infection.

Interestingly, approximately 67% of patients (20/30) with long-term sequelae of COVID-19 were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse IgG or EBV viral capsid antigen IgM [4]. Thus, EBV reactivation may play a role in long-term symptoms in COVID-19 survivors although further study using a large sample size is needed. The authors suggest that most of long-lasting symptoms in COVID-19 survivors following the recovery from SARS-CoV-2 infection might not be directly affected by the virus but probably result from SARS-CoV-2-associated inflammation and EBV reactivation [4].

In the issue, Khani and Entezari-Maleki proposed that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), may be a new therapeutic drug for long-term consequences of COVID-19 survivors [5]. Fluvoxamine has been demonstrated to prevent clinical deterioration in early-stage subjects with COVID-19 [6]. In addition of serotonin transporter inhibition, sigma-1 receptor chaperone in the endoplasmic reticulum (ER) and acid sphingomyelinase might play a role in the mechanisms of beneficial action of fluvoxamine for patients with SARS-CoV-2 infection [6,7,8]. It is also reported that sigma-1 receptor agonists such as fluvoxamine could produce potent anti-inflammatory actions by the prevention of inositol requiring enzyme 1α (IRE1) and X-box binding protein-1 (XBP-1) pathway [9]. Collectively, it is likely that sigma-1 receptor agonists such as fluvoxamine could produce potent anti-inflammatory effects through sigma-1 receptor/IRE1/XBP-1 pathway in the ER [6,7,8,9].

Among the SSRIs, fluvoxamine was the most potent at sigma-1 receptor in the brain [6,7,8]. Given the link between EBV reactivation and XBP-1 [10], it is possible that the potent sigma-1 receptor agonist fluvoxamine may have beneficial effects for long-term consequences in COVID-19 survivors through sigma-1 receptor/IRE1/XBP-1 pathway [4]. Therefore, it is of great interest to examine whether fluvoxamine can improve long-term sequelae in COVID-19 survivors.

Source: Hashimoto Y, Suzuki T, Hashimoto K. Comments to “Fluvoxamine and long COVID-19: a new role for sigma-1 receptor (S1R) agonists” by Khani and Entezari-Maleki. Mol Psychiatry. 2022 Apr 6:1–2. doi: 10.1038/s41380-022-01546-2. Epub ahead of print. PMID: 35388183; PMCID: PMC8985059. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985059/ (Full text)