Tianeptine misuse and addiction: A systematic review of withdrawal, toxicity, and clinical management.

BACKGROUND

Tianeptine is an atypical tricyclic antidepressant with mu-opioid receptor agonist activity. Although marketed as an unregulated "nootropic" in the United States, its use has been increasingly associated with misuse, dependence, and toxicity.

METHODS

We conducted a systematic review following PRISMA 2020 guidelines. MEDLINE, Embase, Cochrane, PsycInfo, and Scopus were searched from inception through July 2025 for human studies describing tianeptine misuse, toxicity, withdrawal, or overdose. Eligible designs included randomized controlled trials, observational studies, and case reports. Data were extracted on clinical presentation and management. Study quality was assessed using Joanna Briggs Institute tools, and findings were narratively synthesized.

RESULTS

Fifty-three publications met inclusion criteria (48 case reports and 5 retrospective series; N = 1055). Among individual cases (n = 52), 26/52 (50%) presented with withdrawal and 23/52 (44%) with overdose. Long-term treatment for withdrawal included buprenorphine 5/26 (19%) and methadone 1/26 (4%). Overdose presentations commonly involved central nervous system depression, respiratory failure, and rhabdomyolysis; among overdose cases with detailed data (n = 22), naloxone was administered in 6/22 (27%), and fatalities occurred in 7/22 (32%). Retrospective studies (n = 1007) described mixed toxicity and withdrawal presentations; 227/1007 (22%) requiring intensive care.

CONCLUSION

Tianeptine misuse is associated with opioid-like dependence, withdrawal, and toxicity. Continued clinical and epidemiological observation is warranted.