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-HT_1A, 5-HT_2A, and 5-HT_2C 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.

Mescaline, the primary bioactive alkaloid found in Peyote and San Pedro cactus, has been used in traditional medicine for centuries and is now attracting renewed interest for clinical applications. The purpose of this systematic review was to search the literature for studies reporting the use of mescaline to address the gap in our understanding of mescaline use and its impact. References were exported from PubMed, Scopus, Embase, and Cochrane. Included studies contained patient data pertaining to mescaline, primary sources for beliefs on the use of mescaline as traditional medicine, and a range of psychiatric conditions. Excluded studies included unpublished studies, animal studies, and studies without English full-texts available. Of 2770 imported references, 66 met the inclusion criteria, with only 10 being found suitable for analysis. Studies reported therapeutic effects such as improvements in depression scales, well-being, nicotine dependence, alcohol use, and obsessions. Bayesian analysis found that certain effects were frequently reported, such as hypertension, headache, nausea, and vomiting. The existing literature on mescaline is limited and of highly variable quality, preventing definitive conclusions regarding the prevalence of psychological and somatic effects from mescaline and mescaline-containing ethnobotanicals. Additional research is needed to determine the safety profile of mescaline. Given the prevalence of Peyote use in the Native American Church, the collaboration of the Native American Church and regional hospitals/poison centers is recommended to create a registry to allow for standardized and clinically applicable data collection on the effects of mescaline in prevalent populations.