The Off-Label Use of Selective Serotonin Reuptake Inhibitors for Sexual Behavior Management: Risks and Considerations

Background: Selective serotonin reuptake inhibitors (SSRIs) are one of the most frequently used medication classes in psychiatry, with many approved and off-label uses. One common side effect of SSRIs is sexual dysfunction, leading to the off-label use of SSRIs to manage inappropriate sexual behaviors in psychiatric settings. However, no official guidelines exist for this off-label use of SSRIs, so a review of this use is warranted. Methods: This review was conducted using the PubMed and Google Scholar databases. Grey literature was considered for inclusion in this review, but only one report by the United Kingdom’s Care Quality Commission was included. Peer-reviewed references discussing the theoretical mechanisms of SSRI-induced sexual dysfunction, case reports/studies examining the off-label use of SSRIs, and reviews discussing relevant disorders like post-SSRI sexual dysfunction (PSSD) were included in this review. Results: The literature proposes that SSRIs act through a variety of serotonin receptors such as 5-HT1A, 5-HT2A, and 5-HT2C to inhibit dopaminergic tone in the mesolimbic and spinal pathways to cause sexual dysfunction. Discussion: SSRIs are frequently considered for off-label use in managing inappropriate sexual behavior, particularly in geriatric patients with dementia, given their superior safety profile compared to antipsychotics in that population. However, the risk and treatment options for PSSD are unclear, which poses a risk for patients taking SRRIs, as it can be a severe and enduring condition. High-quality clinical trials are needed, as the majority of the literature on the topic consists of case reports or theoretical papers.