Two Way Street Between Medicine and Psychiatry in Covid-19

I just found out that, as of the middle of this month, a new category, mental health disorders, has been added to the CDC list of medical conditions associated with higher risk for severe Covid-19 disease and thus, qualifies those in the category for receiving the COVID-19 vaccines . It makes sense. Mood, anxiety, and other neuropsychiatric disorders are known to be connected to a variety of medical conditions, such as diabetes mellitus, thyroid disease, and heart disease. Substance use disorders was already on the list previously. There are medical literature references supporting this:

Fond G, Nemani K, Etchecopar-Etchart D, Loundou A, Goff DC, Lee SW, Lancon C, Auquier P, Baumstarck K, Llorca PM, Yon DK, Boyer L. Association Between Mental Health Disorders and Mortality Among Patients With COVID-19 in 7 Countries: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021 Jul 27:e212274. doi: 10.1001/jamapsychiatry.2021.2274. Epub ahead of print. PMID: 34313711; PMCID: PMC8317055. https://pubmed.ncbi.nlm.nih.gov/34313711/

Ceban F, Nogo D, Carvalho IP, Lee Y, Nasri F, Xiong J, Lui LMW, Subramaniapillai M, Gill H, Liu RN, Joseph P, Teopiz KM, Cao B, Mansur RB, Lin K, Rosenblat JD, Ho RC, McIntyre RS. Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and Death: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021 Oct 1;78(10):1079-1091. doi: 10.1001/jamapsychiatry.2021.1818. PMID: 34319365; PMCID: PMC8319830. https://pubmed.ncbi.nlm.nih.gov/34319365/

It’s also interesting that a large randomized controlled trial of the antidepressant fluvoxamine showed that the agent reduced the need for hospitalization in high-risk outpatients diagnosed with early Covid-19:

Gilmar Reis, Eduardo Augusto dos Santos Moreira-Silva, Daniela Carla Medeiros Silva, Lehana Thabane, Aline Cruz Milagres, Thiago Santiago Ferreira, Castilho Vitor Quirino dos Santos, Vitoria Helena de Souza Campos, Ana Maria Ribeiro Nogueira, Ana Paula Figueiredo Guimaraes de Almeida, Eduardo Diniz Callegari, Adhemar Dias de Figueiredo Neto, Leonardo Cançado Monteiro Savassi, Maria Izabel Campos Simplicio, Luciene Barra Ribeiro, Rosemary Oliveira, Ofir Harari, Jamie I Forrest, Hinda Ruton, Sheila Sprague, Paula McKay, Alla V Glushchenko, Craig R Rayner, Eric J Lenze, Angela M Reiersen, Gordon H Guyatt, Edward J Mills,

Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial,

The Lancet Global Health, 202, ISSN 2214-109X, https://doi.org/10.1016/S2214-109X(21)00448-4.

(https://www.sciencedirect.com/science/article/pii/S2214109X21004484)

Abstract: Summary

Background

Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER trial for acutely symptomatic patients with COVID-19, we aimed to assess the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19.

Methods

This placebo-controlled, randomised, adaptive platform trial done among high-risk symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients from 11 clinical sites in Brazil with a known risk factor for progression to severe disease. Patients were randomly assigned (1:1) to either fluvoxamine (100 mg twice daily for 10 days) or placebo (or other treatment groups not reported here). The trial team, site staff, and patients were masked to treatment allocation. Our primary outcome was a composite endpoint of hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19 up to 28 days post-random assignment on the basis of intention to treat. Modified intention to treat explored patients receiving at least 24 h of treatment before a primary outcome event and per-protocol analysis explored patients with a high level adherence (>80%). We used a Bayesian analytic framework to establish the effects along with probability of success of intervention compared with placebo. The trial is registered at ClinicalTrials.gov (NCT04727424) and is ongoing.

Findings

The study team screened 9803 potential participants for this trial. The trial was initiated on June 2, 2020, with the current protocol reporting randomisation to fluvoxamine from Jan 20 to Aug 5, 2021, when the trial arms were stopped for superiority. 741 patients were allocated to fluvoxamine and 756 to placebo. The average age of participants was 50 years (range 18–102 years); 58% were female. The proportion of patients observed in a COVID-19 emergency setting for more than 6 h or transferred to a teritary hospital due to COVID-19 was lower for the fluvoxamine group compared with placebo (79 [11%] of 741 vs 119 [16%] of 756); relative risk [RR] 0·68; 95% Bayesian credible interval [95% BCI]: 0·52–0·88), with a probability of superiority of 99·8% surpassing the prespecified superiority threshold of 97·6% (risk difference 5·0%). Of the composite primary outcome events, 87% were hospitalisations. Findings for the primary outcome were similar for the modified intention-to-treat analysis (RR 0·69, 95% BCI 0·53–0·90) and larger in the per-protocol analysis (RR 0·34, 95% BCI, 0·21–0·54). There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group in the primary intention-to-treat analysis (odds ratio [OR] 0·68, 95% CI: 0·36–1·27). There was one death in the fluvoxamine group and 12 in the placebo group for the per-protocol population (OR 0·09; 95% CI 0·01–0·47). We found no significant differences in number of treatment emergent adverse events among patients in the fluvoxamine and placebo groups.

Interpretation

Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital.

Funding

FastGrants and The Rainwater Charitable Foundation.

Translation

For the Portuguese translation of the abstract see Supplementary Materials section.

Covid-19 pneumonia affects the brain by causing hypoxia and inflammatory reactions, leading to neurologic dysfunction. Mental health disorders may be partly caused by inflammation. Depressed persons may not protect themselves from Covid-19 because they’re apathetic and hopeless. It’s a two-way street. It’s like Dr. Wes Ely, MD, MPH says:

The lung bone is connected to the brain bone

E. Wesley Ely, MD, MPH

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