(20) Methadone as Treatment for Tianeptine Withdrawal

Background & Introduction: Tianeptine is a tricyclic antidepressant prescribed in several countries for the treatment of depression and anxiety; however, it is not approved by the U.S. Food and Drug Administration (FDA). In addition to its antidepressant properties, tianeptine exhibits mu-opioid receptor agonist activity, which can lead to dependence and opioid-like withdrawal symptoms upon abrupt discontinuation. Several case reports have described the management of tianeptine withdrawal using medications such as benzodiazepines, antiemetics, buprenorphine-naloxone, and, in hospital settings, methadone1,2. Despite increasing community access, awareness among healthcare providers regarding tianeptine’s pharmacologic effects, toxicity, and withdrawal presentation remains limited. Often referred to as “gas station heroin,” it can be sold under brands such as ZaZa or Tianna Red3. This case report aims to raise awareness of tianeptine withdrawal and highlight methadone as a potential treatment option for individuals with tianeptine use disorder.

Case Description: A 32-year-old male with alcohol use disorder in remission, ADHD, unspecified depression, and anxiety presented for withdrawal management of tianeptine use disorder. He reported taking three to six bottles (twenty pills per bottle) of tianeptine daily for two years, purchased from a local smoke shop to self-treat depression and anxiety. His goal was cessation due to financial strain. On exam, he exhibited anxiety, dilated pupils, sweating, lacrimation, and rhinorrhea, with stable vitals. The Clinical Opiate Withdrawal Scale (COWS) was initiated, and addiction medicine was consulted. Due to significant opioid-like withdrawal symptoms, a rapid methadone induction and taper were started. The patient declined to be on long-term methadone at that time. On day one, he received 20 mg followed by 10 mg and 10 mg doses, with marked symptom improvement. Methadone was decreased by 10 mg daily. The patient left via patient-directed discharge before completing the taper on day three. After discharge, he continued to have tianeptine use and withdrawal symptoms when he did not have access to tianeptine. After visiting multiple clinics and treatment programs, he independently established care at a methadone clinic, where he stabilized on 32 mg daily.

Conclusion & Discussion: This case highlights the opioid-like withdrawal syndrome associated with tianeptine use, consistent with its mu-opioid receptor activity. It also demonstrates the effectiveness of methadone for acute stabilization and as a potential maintenance therapy for individuals with tianeptine use disorder. Increased education and awareness among healthcare providers are crucial to ensure timely recognition and appropriate management of patients using this substance. A key limitation in current practice is the lack of standardized treatment guidelines for tianeptine withdrawal given multiple medication options, uncertainty around optimal dosing of treatment options and the wide variability in over-the-counter tianeptine potencies. As access to substances such as tianeptine continues to expand, clinical education and research are important for improving patient outcomes.

References: 1. Farsani A, Reyes C. Tianeptine’s obscured withdrawal, presentation, and treatment. Cureus. June 17, 2024. Accessed October 24, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC11254389/.
2. Rawal VY;Gallardo M;Henderson K;Hall OT;Klisovic N;Sikic-Klisovic E; Severe tianeptine withdrawal symptoms managed with medications for opioid use disorder: A case report. Journal of addictive diseases. Accessed October 24, 2025. https://pubmed.ncbi.nlm.nih.gov/38095574/.
3. Wagner ML;Pergolizzi J;LeQuang JAK;Breve F;Varrassi G; From antidepressant tianeptine to street drug zaza: A narrative review. Cureus. Accessed October 24, 2025. https://pubmed.ncbi.nlm.nih.gov/37485121/.