SSRIs show promise in easing post-COVID struggles, Dutch study reveals

In an exploratory study published in the journal Scientific Reports, researchers from the Netherlands investigated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of 95 patients with post-coronavirus disease 2019 (COVID-19) syndrome (PCS). They explored the neurobiological mechanisms underlying the response. They found that all the patients showed improved well-being and decreased symptoms, and about two-thirds of the patients showed a good-to-strong response to SSRIs.

Study: Treatment of 95 post-Covid patients with SSRIs. Image Credit: Natallia Boroda / ShutterstockStudy: Treatment of 95 post-Covid patients with SSRIs. Image Credit: Natallia Boroda / Shutterstock


PCS emerged in 2020 as a complex and poorly understood health concern, affecting about a hundred million individuals worldwide. Among the 200 different symptoms associated with PCS, the key ones are sensory overload, brain fog, headache, chronic fatigue, dyspnea, dysautonomia, muscle pain and weakness, palpitations, and disturbed sleep. As per the literature, these symptoms are attributed to increased pro-inflammatory cytokines, autoimmune reactions, microclot formation, neuroinflammation, as well as reactivation of certain viruses.

SSRIs are commonly indicated for mental disorders but can influence the immune system by modulating the hypothalamic–pituitary–adrenal (HPA) axis, interacting with the kynurenine pathway (KP), as well as by preventing inflammation. Evidence suggests that treatment with SSRIs during COVID-19 may reduce the severity of infection and help prevent PCS. Given the current lack of medications to treat PCS and the dearth of studies evaluating the potential of SSRIs in this regard, researchers in the present study aimed to evaluate the effect of SSRI treatment on patients with PCS and probe the underlying mechanisms.

About the study

In the prospective segment of the study, about 101 completed pretreatment questionnaires (on demographics, history, and symptoms) were collected from patients interested in SSRI treatment for PCS. The inclusion criteria were a history of transient COVID-19 proven by polymerase chain reaction or antigen test, followed by PCS symptoms. Patients on long-term SSRI treatment for depression, those involved in other drug studies, and those with severe SSRI-related adverse events were excluded from the study. Out of the 95 included patients, three developed PCS, as confirmed by their physician. The mean age of the participants was 43 years, and the females in the group were 5.8 times the number of men. In the retrospective segment of the study, completed questionnaires were obtained from 61 participants who were initiated on SSRIs prior to the commencement of the study.

The patients were advised to consult their physician for treatment initiation. The dose for depression was used as a guideline and was further varied on a case-to-case basis, considering the observed adverse effects and potential drug interactions. The recommended drugs included SSRIs such as fluvoxamine, citalopram, escitalopram, citalopram, and fluoxetine, as well as venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI). After four to six weeks of treatment, the participants filled out another questionnaire regarding the outcomes.

The treatment outcomes were evaluated using three measures: (i) open question outcomes (n=93), (ii) scoring list (n=77), and (iii) Bell’s functionality score (n=80). The answers to the open-ended question on SSRI treatment were rated as: strong improvement, good improvement, reasonably good improvement, moderate improvement, and no improvement. In the score list, patients were asked to grade the severity of PCS symptoms on a scale of 0 (least) to 10 (highest), both before and during treatment. Statistical analysis included the use of Bayes factor (BF), analysis of variance (ANOVA), and Spearman’s rank correlation, among other tools.

Results and discussion

As per the pretreatment score list, the patient-reported symptoms were as follows: brain fog (100%), fatigue (100%), sensory overload (98.7%), headache (90.9%), palpitations (88.3%), muscle weakness (85.7%), muscle pain and spasm (80.5%), post-exertional malaise (PEM, 100%), and dissociative symptoms (n=14). As per the post-treatment scores, SSRI treatment showed a reduction in symptoms, with a maximal reduction observed in brain fog, sensory overload, and PEM, while a minimal reduction was seen in muscle pain and weakness.

As per the open-question results, irrespective of the SSRI used, a reduction in symptoms was observed in 63.4% of patients post-treatment. The improvement was rated as reasonably good in 26.9% of patients, good in 29% of patients, and strong in 7.5%. Additionally, a decrease in PEM, depression, loss of dissociative symptoms, and an improvement in sleep were observed among the treated patients. The results were found to be consistent even in patients continuing the treatment for more than six months. The SSRI treatment also showed a positive effect on Bell scores. Additionally, the three effect measures were found to correlate significantly.

Nine patients who did not respond to SSRI treatment were found to have a greater severity of COVID-19 symptoms than those who did.

The safety analysis suggests that out of the 95 patients studied, 30 experienced severe side effects initially, while 52 participants experienced mild side effects, and 13 did not experience any side effects. Randomized controlled trials conducted in the future could help rule out a potential placebo effect in the observed results.

Existing literature describes seven probable neurobiological mechanisms underlying the positive effect of SSRIs on PCS. The present study provides clinical evidence for five of these mechanisms, including the effect of SSRIs on the HPA axis, brain stem, ANS, CNS, and circulatory system, and emphasizes the need for further research in the area.


In conclusion, the study provides evidence of SSRIs' efficacy in treating PCS. It highlights the need to identify potential PCS treatment options and explore the underlying mechanisms to aid better patient health outcomes.

Journal reference:
Dr. Sushama R. Chaphalkar

Written by

Dr. Sushama R. Chaphalkar

Dr. Sushama R. Chaphalkar is a senior researcher and academician based in Pune, India. She holds a PhD in Microbiology and comes with vast experience in research and education in Biotechnology. In her illustrious career spanning three decades and a half, she held prominent leadership positions in academia and industry. As the Founder-Director of a renowned Biotechnology institute, she worked extensively on high-end research projects of industrial significance, fostering a stronger bond between industry and academia.  


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