Neuropsychiatric drugs against COVID-19: What is the clinical evidence?

Since the beginning of the coronavirus disease (COVID)-19 pandemic, the need for effective treatments for COVID-19 led to the idea of "repurposing" drugs for antiviral treatment. Several antipsychotics and antidepressants have been tested for in vitro activity against the severe acute respiratory syndrome coronavirus 2. Chlorpromazine, other phenothiazine antipsychotics, and the antidepressant fluoxetine were found to be rather potent in these studies. However, whether effective plasma concentrations can be obtained with clinically accepted doses of these drugs is not clear. Data of COVID-19 patients are not yet available but several clinical studies are currently underway. The specific serotonin reuptake inhibitor fluvoxamine is a potent Sigma-1 receptor agonist and reduces inflammation in animal models of cytokine-stress. Accordingly, fluvoxamine treatment was superior to placebo in reducing impaired respiratory function and other symptoms of inflammation in COVID-19 patients in a placebo-controlled clinical study and another open clinical trial. The beneficial effects of fluvoxamine on the course of COVID-19 were recently confirmed in a large placebo-controlled double-blind trial with several hundred patients. Inflammation represents a major risk factor for many psychiatric disorders which explains the high susceptibilitiy of COVID- 19 patients for psychiatric diseases. Many antidepressants and antipsychotics possess anti-inflammatory properties independent of sigma-1 activity which might be important to reduce psychiatric symptoms of COVID-19 patients and to improve respiratory dysfunction and other consequences of inflammation. This might explain the rather unspecific benefit which has been reported for several cohorts of COVID-19 patients treated with different psychotropic drugs. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

New NICE draft guidance encourages less use of SSRIs for mild to moderate depression

Sarah Jane Palmer uses her personal experience of mental health conditions to explore the new draft guidance on mild to moderate depression

Differential Molecular Responses of Zebrafish Larvae to Fluoxetine and Norfluoxetine

The occurrence of psychopharmaceuticals in aquatic ecosystems is a growing problem. Fluoxetine (FL) and its metabolite norfluoxetine (NF) are selective serotonin reuptake inhibitors. Although they may be potentially harmful to non-target species, available knowledge on the effects of NF is sparse, relative to FL. This study aimed at contributing to the body of knowledge about the modes-of-action (MoA) of these compounds and their underlying mechanisms eliciting hazardous effects during the early development of the teleost model zebrafish (Danio rerio). One hour post-fertilisation (hpf), embryos were exposed up to 80 hpf to these compounds at levels found in surface waters and higher (FL, 0.0015 and 0.05 µM;NF, 0.00006 and 0.0014 µM). Developmental anomalies were observed at 8, 32 and 80 hpf. Larvae were collected at 80 hpf to assess the expression of 34 genes related to FL and NF MoA and metabolism, using qPCR (quantitative reverse transcription PCR). Results showed that both compounds elicited an increased frequency of embryos exhibiting abnormal pigmentation, relative to controls. Gene expression alterations were more pronounced in FL- than in NF-exposed larvae. Cluster Analysis revealed two groups of genes discriminating between the drugs. for their marked opposing responses. Globally, downregulation of gene expression was typical of FL, whilst upregulation or no alteration was found for NF. These clusters identified were linked to the adrenergic pathway and to the retinoid and peroxisome proliferator-activated nuclear receptors. Overall, our data contradict the prevailing notion that NF is more toxic than FL and unveiled the expression levels of genes drd2b, 5-ht2c and abcc2 as possible markers of exposure to FL.

Trazodone Add-on in COVID-19-related Selective Serotonin Reuptake Inhibitor-resistant Post-traumatic Stress Disorder in Healthcare Workers: Two Case Reports.

COVID-19 represents a significant stress factor for all people worldwide due to several factors, including quarantine, lockdowns, fear of contagion, deaths, and other traumatic events. However, the healthcare workers (HCWs) have paid the higher price of this pandemic in terms of fatalities, contagions, and psychological well-being. Studies suggest that this particular population is at increased risk of developing a severe post-traumatic stress disorder (PTSD). The early diagnosis and timely treatment of PTSD in HCWs may restore well-being and significantly impact health services functioning, reducing burnout, days spent far from work, disrupted personal and team empowerment, and worse job performances. In the present article, we reported on two cases of HCWs directly involved in the treatment of COVID-19 patients who showed selective serotonin reuptake inhibitor-resistant PTSD, which was successfully treated with extended-release trazodone TRZ ContramidⓇ add-on.

Rapid response to selective serotonin reuptake inhibitors in post-COVID depression.

The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. After COVID-19, depression was reported in 40% of patients at one-, three-, and six-months follow-up. Emerging literature suggests anti-inflammatory and antiviral properties of antidepressants in the treatment of SARS-CoV-2. We aim to investigate the efficacy of Selective Serotonin Reuptake Inhibitor (SSRI) in treating post-COVID depression. We included 60 patients affected by a major depressive episode and treated with SSRI in the six months following recovery from COVID. The severity of depression was rated at baseline and after four weeks on the Hamilton Depression Rating Scale (HDRS). Response to treatment was considered when the patients achieved a 50% HDRS reduction. To investigate changes of depressive symptomatology over time, repeated measures ANOVAs according to clinical variables were performed. We found that 55 (92%) patients showed a clinical response to antidepressant. Patients showed a significant decrease over time of HDRS score (baseline HDRS = 23.37 ± 3.94, post-treatment HDRS = 6.71±4.41, F = 618.90, p < 0.001), irrespectively of sex, previous psychiatric history, previous history of mood disorder, and SSRI type. This is the first study to explore the SSRI efficacy in post-COVID depression, suggesting rapid antidepressant effects in most patients. SSRIs treatment could contribute to the rapid antidepressant response by directly targeting the neuroinflammation triggered by SARS-CoV-2. We suggest screening psychopathology of COVID-19 survivors to diagnose emergent depression and pharmacologically treat it to reduce the disease burden and related years of life lived with disability.