Plant-derived bioactives in depression-related and antidepressant-associated sexual dysfunction: a narrative review

Sexual dysfunction related to depression and antidepressant treatment is clinically important yet underrecognized, affecting adherence, intimate functioning and quality of life. Depression can impair desire, arousal, orgasm and satisfaction before pharmacotherapy, while serotonergic antidepressants may further disturb these domains during treatment, complicating causal attribution and underscoring the need to distinguish depression-related sexual dysfunction from antidepressant-associated sexual dysfunction (AISD). Plant-derived bioactives have attracted interest because several engage systems relevant to both mood and sexual response, including monoaminergic, inflammatory/oxidative, HPA-axis, autonomic and nitric oxide-mediated vascular pathways. We conducted a narrative review based on targeted searches of PubMed/MEDLINE, Web of Science and Scopus through June 2026, synthesizing mechanistic and clinical evidence for selected candidates by phenotype specificity to separate direct AISD studies from adjacent clinical or preclinical evidence and mechanistic plausibility. Saffron provides the most coherent AISD-specific signal, supported by small randomized trials in women and men with fluoxetine-associated sexual dysfunction. Maca shows a narrower signal in female SSRI/SNRI-associated sexual dysfunction, particularly in postmenopausal women. Rosa damascena remains preliminary, whereas Ginkgo biloba shows inconsistent controlled evidence and interaction concerns. Panax ginseng, pomegranate and dietary nitrates are mechanistically plausible through endothelial and nitric oxide pathways but lack direct AISD evidence. Overall, current evidence supports mechanistic plausibility and preliminary phenotype-specific signals rather than established efficacy. Plant-derived bioactives are best positioned as investigational adjunctive nutritional modulators within evidence-based psychiatric and sexual-medicine care, pending larger trials with standardized preparations, validated sexual-function outcomes, sex-specific analyses and mechanism-oriented biomarkers.