When Buprenorphine Was Not Enough: Methadone Treatment of Tianeptine Use Disorder

Introduction: Tianeptine, approved in 25 countries for depression treatment, is an atypical tricyclic with clinically relevant µ-opioid receptor agonist activity at high doses. Tianeptine is not approved by the Food and Drug Administration in the United States, and until recently, was illegally marketed as an over-the-counter “supplement.” Tianeptine’s pharmacological activity at the µ-opioid receptor and opioid withdrawal-like syndrome have prompted clinicians to use buprenorphine and methadone to manage tianeptine withdrawal and treat tianeptine use disorder. This case report describes successful treatment of tianeptine use disorder using methadone in a patient without an active opioid use disorder (OUD). Case Report: A 51-year-old woman with hypothyroidism, major depressive disorder, and OUD in sustained remission presented to an opioid treatment program (OTP) seeking treatment for tianeptine use disorder. The patient reported that 24 mg/d buprenorphine was ineffective in managing her tianeptine cravings and withdrawal symptoms. Her stated goal was to abstain from tianeptine use. The patient initiated methadone at 30 mg/d and reached a steady-state methadone dose of 86 mg/d. She has abstained from tianeptine for 3 years and demonstrated sustained treatment stability allowing for multiple weeks of take-home methadone doses. Discussion: Patients with tianeptine use disorder, and with use disorders resulting from regular use of substances characterized as nonopioid but with µ-opioid receptor agonist effects, may follow a similar clinical course to patients with OUD. This case highlights an emerging treatment gap for use disorders involving substances with clinically relevant µ-opioid receptor agonist effects that do not fall within the OUD-based OTP treatment framework.