Gas station heroin- tianeptine and its impact: a systematic review and exploratory analysis

Tianeptine, a drug approved in some countries for the treatment of major depressive disorder, has raised significant public health concerns due to its potential for misuse and addiction. Its activity at the mu-opioid receptor along with its availability as a dietary supplement in certain regions, raises concerns about overdose, toxicity, and its contribution to the opioid crisis. Despite recognition of its addictive potential for over two decades, systematic data on misuse patterns, associated risk factors, and effective treatment strategies remain limited. This study investigates demographic/regional trends in tianeptine misuse, examines the influence of dosage, administration routes, and co-administration with other substances on overdose risk, and evaluates the efficacy of naloxone and other treatments in managing tianeptine toxicity and withdrawal symptoms.

Following PRISMA 2020 guidelines, our systematic review (PROSPERO ID: CRD42024521671) searched PubMed, Embase, PsycINFO, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrials.gov. The quality of included studies was assessed using the JBI checklist, and exploratory analysis was conducted in R (v.4.3.3). From 1,562 identified records, 25 studies met inclusion criteria.

Tianeptine misuse demonstrated notable regional variations, with North America accounting for 40/52 (76.92%) of cases, followed by Asia 8/52 (15.38%) and Europe 4/52 (7.69%) (X²=44.9231, p < 0.0001). The majority of users were male 29/52 (55.77%) (X²=0.6923, p = 0.4054), and oral ingestion was the predominant route 37/52 (71.15%), while intravenous use accounted for 5/52 (9.62%) (X²=88.3846, p < 0.0001). Habitual misuse was documented in 30/52 (57.69%) of cases (X²=1.2308, p = 0.2673). Overdose occurred in 18/52 (34.62%) of cases (X²=4.9231, p = 0.0265), frequently associated with high doses up to 20 g daily and co-administration with alcohol 6/52 (11.54%) or benzodiazepines 5/52 (9.62%) (X²=68.5932, p < 0.0001). Naloxone reversed symptoms in 9/52 (17.31%) of treated cases (X²=22.2308, p < 0.0001). Withdrawal symptoms were observed in 22/52 (42.31%) of cases (X²=21.3846, p < 0.0001), with management strategies including buprenorphine 4/52 (7.69%) and supportive care 4/52 (7.69%) (X²=44.0000, p < 0.0001).

Tianeptine misuse, characterized by escalating doses, habitual use, and co-administration with other substances, poses significant risks. Its easy availability and lack of regulation further exacerbate its public health impact. Targeted prevention, regulation, and treatment interventions are urgently needed to address these challenges.