Key PointsQuestionDoes fluvoxamine, a selective serotonin reuptake inhibitor and σ-1 receptor agonist, prevent clinical deterioration in outpatients with acute coronavirus disease 2019 (COVID-19)?FindingsIn this randomized trial that included 152 adult outpatients with confirmed COVID-19 and symptom onset within 7 days, clinical deterioration occurred in 0 patients treated with fluvoxamine vs 6 (8.3%) patients treated with placebo over 15 days, a difference that was statistically significant.MeaningIn this preliminary study, adult outpatients with symptomatic COVID-19 treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days; however, determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.

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Objective-To examine gender and age differences in Attention-Deficit/Hyperactivity Disorder (ADHD) symptom endorsement in a large community-based sample.Method-Families with four or more full siblings ascertained from Missouri birth records completed telephone interviews regarding lifetime DSM-IV ADHD symptoms and the Strengths and Weaknesses of ADHD-Symptoms and Normal-behavior (SWAN) questionnaire for current ADHD symptoms. Complete data were available for 9380 subjects aged 7 to 29 years. Lifetime and current DSM-IV-like ADHD diagnoses were assigned by the DSM-IV symptom criterion. Linear regression was used to examine sex and age effects on SWAN ADHD symptom scores. Logistic regression was used to examine sex and age effects on specific ADHD diagnoses. Fractional polynomial graphs were used to examine ADHD symptom count variations across age.Results-Overall prevalence of current DSM-IV-like ADHD was 9.2% with a male:female ratio of 2.28:1. The prevalence of DSM-IV-like ADHD was highest in children. Gender differences in DSM-IV-like ADHD subtype prevalences were highest in adolescents. On average, individuals with lifetime DSM-IV-like ADHD diagnoses had elevated current ADHD symptoms even as adolescents or adults.Conclusions-Lower male:female ratios than reported in some clinic-based studies suggest that females are under-diagnosed in the community. Although they may no longer meet the full symptom criterion, young adults with a history of lifetime DSM-IV-like ADHD maintain higher levels of ADHD symptoms compared to the general population. The use of age-specific diagnostic criteria should be considered for DSM-V and ICD-11.

This study provides population-based evidence for clinically significant elevations of autistic traits in children meeting diagnostic criteria for ADHD. These results have implications for the design and interpretation of studies of both disorders.

Fluvoxamine is a well-tolerated, widely available, inexpensive selective serotonin reuptake inhibitor that has been shown in a small, double-blind, placebo-controlled, randomized study to prevent clinical deterioration of patients with mild coronavirus disease 2019 (COVID-19). Fluvoxamine is also an agonist for the sigma-1 receptor, through which it controls inflammation. We review here a body of literature that shows important mechanisms of action of fluvoxamine and other SSRIs that could play a role in COVID-19 treatment. These effects include: reduction in platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, regulation of inositol-requiring enzyme 1α-driven inflammation and increased melatonin levels, which collectively have a direct antiviral effect, regulate coagulopathy or mitigate cytokine storm, which are known hallmarks of severe COVID-19.