Purpose of Review <p>Despite increased media attention and increasing prohibitions for tianeptine products in the United States, we lack basic information about morbidities related to their use. The review aimed to identify the prevalence of US-based clinical case reports involving tianeptine products; document patient characteristics, co-used substances, and use motivations; quantify morbidities attributed to tianeptine; and characterize symptoms. Findings are discussed within a policy context. We conducted a systematic review between February-April 2024 of US-based case reports involving tianeptine products following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodological checklist. We used Covidence for screening, data extraction, quality assessment, and consensus.</p> Recent Findings <p>Out of 1086 records, 26 were included in the final sample, published between 2016–2024. Patients (<i>N</i> = 28) were primarily male (82.1%) with a mean age of 34.3&#xa0;years; eight patients had used tianeptine for ≥ 1&#xa0;year. Products included capsules and sodium powder, with two reporting injection. Patients used tianeptine for anxiolytic and euphoric effects, and as an opioid replacement. Dependence and addiction were the most common morbidities attributed to tianeptine with naloxone used in eight cases and buprenorphine/naloxone used in four; 113 symptoms were identified across patients, though only two cases included toxicology screens to confirm tianeptine use.</p> Summary <p>Despite lacking critical information, cases reviewed here indicate that there is some risk associated with tianeptine product use, with dependence, addiction, toxicity, and respiratory depression most noteworthy. However, there remain gaps between adverse event reporting, media narratives, and policymaking that can only be reconciled by systematic investigations.</p>