P.0404 Rapid antidepressant response to first-line selective serotonin reuptake inhibitors in post-COVID-19 depression

ABSTRACT

Introduction: Depression was reported in 30–40% of patients at one, three, and six months following COVID-19 [1]. The host immune response to SARS-CoV-2 infection and related severe systemic inflammation seems to be the main mechanism contributing to the development of post-COVID depression. Emerging literature suggests anti-inflammatory and antiviral properties of antidepressants in the treatment of SARS-CoV-2 infection [2]. We hypothesized that post-COVID depression, triggered by infection and sustained by systemic inflammation, could particularly benefit from antidepressants. Thus, the present study aims to investigate the efficacy of SSRI in treating post-COVID depression. Methods: We included 58 adults patients who showed depressive episodes in the six months following COVID-19. We excluded patients if they showed other psychiatric comorbidities, ongoing treatment with antidepressants or neuroleptics, somatic disease and medications known to affect mood. The severity of depression was rated at baseline and after for four weeks from the start of the treatment on the Hamilton Depression Rating Scale (HDRS) and response was considered when the patients achieved a 50% HDRS reduction after treatment. Statistical analyses to compare group means and frequencies (Student's t-test, Pearson χ2 test) were performed. To investigate changes in HDRS scores over time, repeated measures ANOVAs (according to sex, mood disorder history, and antidepressant molecule) were performed. Results: We found that 53 (91%) patients showed a clinical response to antidepressant treatment. Age, sex, mood disorder history, and hospitalization for COVID did not affect the response rate. Patients were treated with sertraline (n=26), citalopram (n=18), paroxetine (n=8), fluvoxamine (n=4), and fluoxetine (n=2). From baseline to follow-up, patients showed a significant decrease over time of HDRS score (F=618.90, p<0.001), irrespectively of sex (0.28, p=0.599), mood disorder history (F=0.04, p=0.834), and drug used (F=1.47, p=0.239). Discussion: Common knowledge highlights that among antidepressant-treated patients, response rates are moderate (40–60%). On the contrary, we observed a rapid response to the first-line antidepressants in more than 90% of patients irrespectively of clinical variables, thus suggesting a higher antidepressant response rate in post-COVID depression. The pathophysiology of post-COVID neuropsychiatric sequelae mainly entails severe systemic inflammation and subsequent neuroinflammation. In this context, we have previously found that one and three months after COVID-19, the severity of depression was predicted by the baseline systemic immune-inflammation index (SII) [3,4]. Furthermore, we found a protective effect of the IL-1β and IL-6 receptor antagonist against post-COVID depression possibly associated with their effect in dampening SII [5]. Mounting evidence suggests that antidepressants may a) decrease markers of inflammation;b) may inhibit acid sphingomyelinase preventing the infection of epithelial cells with SARS-CoV-2;c) may prevent the COVID-19 related cytokine storm by stimulating the σ-1 receptor;d) may exert antiviral effects via lysosomotropic properties;e) may inhibit platelets activation [2]. In conclusion, we hypothesized that post-COVID depression could particularly benefit from antidepressants since this molecules have anti-inflammatory and antiviral properties, pass the BBB and accumulate in the CNS, thus preventing the neuro-inflammation triggered by SARS-CoV-2 and associated with post-COVID depression. No conflict of interest