Scientists from China analyzed reports of adverse reactions to fluoxetine, a widely prescribed antidepressant from the selective serotonin reuptake inhibitor (SSRI) class. These drugs increase the availability of serotonin, a chemical messenger in the brain that helps regulate mood. The study was published in the journal Progress in Neuropsychopharmacology & Biological Psychiatry.
The authors, led by Jun Li and Xing Wang (corresponding author Honglin Hu) of Nanchang University, examined 997 reports of sexual disorders associated with fluoxetine. The data came from the FDA Adverse Event Reporting System (FAERS), a public database where patients and doctors voluntarily report reactions to drugs. Records from 2004 to 2025 were selected in which fluoxetine was listed as the primary suspect drug.
Decreased libido and erectile dysfunction were mentioned most often. However, the highest reporting intensity was shown by specific symptoms: complete inability to achieve orgasm, diminished orgasmic sensation and genital numbness. These conditions appeared in the reports disproportionately often compared with traditional indicators of sexual disorders.
The researchers then estimated the time to symptom onset using only records with complete dates for the start of treatment and the occurrence of the side effect. The timing varied widely. Some conditions, such as prolonged painful erection or persistent genital arousal, occurred in the first days of use. Loss of libido usually appeared after four to five months. And genital numbness and inability to achieve orgasm were often recorded more than two years after continuous use of the drug.
To understand the biological mechanisms, the scientists used network toxicology, a computational method that matches data on drug interactions with proteins and genes. They compiled a list of human proteins that interact with fluoxetine and a separate list of proteins and genes associated with sexual dysfunction. The intersection comprised 56 genetic targets. They are involved in serotonin and dopamine metabolism pathways, as well as in processes of inflammation, immune response and cell death.
Among these targets, two central proteins stood out: IL10, which regulates inflammation and immunity, and TP53, which responds to cellular stress and triggers programmed death of damaged cells. Molecular docking modeling, which predicts how a drug molecule fits into a protein structure (like a key in a lock), showed that fluoxetine can bind to both proteins, especially strongly to IL10. This suggests that the drug may directly affect their function.
The researchers note limitations. The FDA database is based on voluntary reports, so it does not reflect the true frequency of symptoms. It lacks complete data on doses, duration of treatment and other medications taken. In addition, depression itself is associated with inflammation, so it is difficult to separate the effect of the drug from the influence of the underlying disease. Finally, computer models remain theoretical: they show the possibility of binding but do not confirm how the drug behaves in a living organism. Laboratory experiments and clinical trials are needed for verification.
The authors emphasize that the identified associations are statistical and model-based in nature and do not prove that fluoxetine causes these effects through the mechanisms described. The results only outline directions for further research.