Tianeptine (marketed as Coaxil or Stablon) is an atypical tricyclic drug used as an antidepressant in Europe, Asia, and Latin America. In the United States, tianeptine is not approved by the Food and Drug Administration (FDA) for medical use and is an unscheduled pharmaceutical agent* (1). Animal and human studies show that tianeptine is an opioid receptor agonist (2). Several case studies have reported severe adverse effects and even death from recreational abuse of tianeptine (3–5). To characterize tianeptine exposures in the United States, CDC analyzed all exposure calls related to tianeptine reported by poison control centers to the National Poison Data System (NPDS)^† during 2000–2017. Tianeptine exposure calls, including those for intentional abuse or misuse, increased across the United States during 2014–2017, suggesting a possible emerging public health risk. Most tianeptine exposures occurred among persons aged 21–40 years and resulted in moderate outcomes. Neurologic, cardiovascular, and gastrointestinal signs and symptoms were the most commonly reported health effects, with some effects mimicking opioid toxicity. A substantial number of tianeptine exposure calls also reported clinical effects of withdrawal. Among 83 tianeptine exposures with noted coexposures, the most commonly reported coexposures were to phenibut, ethanol, benzodiazepines, and opioids.

CDC used NPDS data to review all tianeptine exposure telephone calls reported by U.S. poison control centers during 2000–2017. Calls for drug information or identification were excluded. Trends in exposure by year were compiled for all tianeptine exposure calls and for calls related to intentional abuse or misuse. Descriptive statistics were compiled for all exposure calls by U.S. Census region (Midwest, Northeast, South, and West),^§ caller source (self or health care professional), demographics (sex and age group), exposure type (intentional, unintentional, withdrawal, or unknown/other), exposure route (ingestion, parenteral, or inhalation), and coexposures. Tianeptine-only exposures were defined as those that reported only tianeptine use with no other substances. Tianeptine-only exposures (excluding withdrawal-associated calls) were analyzed for reported related clinical effects by body systems, performed therapies, and level of care (evaluated, treated, and released from the emergency department (ED), admission to noncritical care units, admission to critical care units, or other).

Exposure medical outcomes were classified according to American Association of Poison Control Centers (https://www.aapcc.org/) definitions as either no effect, minor outcome, moderate outcome, severe outcome, or death. Minor outcomes were defined as symptoms that were minimally bothersome to the patient, usually resolved rapidly, and often involved skin or mucous membrane manifestations, after which the patient returned to a preexposure state of well-being with no residual disability or disfigurement. Moderate outcomes were defined as symptoms that were more pronounced, more prolonged, or of a more systemic nature than minor symptoms but were not life threatening; usually requiring some form of treatment, after which the patient returned to a preexposure state of well-being with no residual disability or disfigurement. Major outcomes were defined as symptoms that were life threatening or resulted in a significant residual disability or disfigurement. Withdrawal-associated tianeptine calls were analyzed separately for clinical effects and performed therapies. Summaries of two cases reported in 2016 are presented for illustrative purposes (Supplementary Table, https://stacks.cdc.gov/view/cdc/57404).

Frequencies for categorical variables and mean values for continuous variables were calculated using statistical software. Tests for the trend for all tianeptine exposure calls and for calls related to intentional abuse or misuse during 2014–2017 were performed. Fisher’s exact test was used to test for associations between reported outcome severity and tianeptine-only exposures versus tianeptine with coexposures, age group, and sex. Statistical significance was defined as p<0.05.

During 2000–2017, NPDS received 218 calls related to tianeptine exposure, including one from outside the United States. Tianeptine-only exposures, excluding 29 withdrawal-associated calls, accounted for 114 (52.3%) calls. During the first 14 years of the study period (2000–2013), NPDS received a total of 11 tianeptine exposure calls. From 2014 through 2017, there was a statistically significant increase in calls related to exposure (p<0.001) and intentional abuse or misuse (p<0.001). The total number of tianeptine exposure calls increased from five in 2014 to 38 in 2015, 83 in 2016, and 81 in 2017 (Figure). The majority of calls (91.2%) came from health care providers; by U.S. Census region, the highest percentage of calls came from the South (34.6%). Among 213 (97.7%) exposure calls for which information on age was available, the mean age was 35 years (range = 1–80 years) (Table 1).

Among the 114 tianeptine-only exposures, excluding withdrawal-related calls, the most commonly reported related clinical effects were neurologic (48.3%), cardiovascular (32.5%), and gastrointestinal (10.5%) (Table 2). The most commonly administered therapies included fluids (35.1%), benzodiazepines (27.2%), and oxygen (10.5%) (Table 2). Among the 105 exposure calls for which level of care was reported, 46 (44%) persons were treated, evaluated, and released from the ED, and 25 (24%) were admitted to a critical care unit. Among the 93 tianeptine-only exposures with a known medical outcome, 50 (54%) had moderate outcomes. No deaths were reported.

Poison control centers reported 29 withdrawal-associated calls. Among those, tianeptine was the only substance reported to be associated with withdrawal in 21 (72.4%) calls; among those 21 calls, the most frequently reported signs and symptoms were agitation (33.3%), nausea (33.3%), vomiting (19%), tachycardia (19.1%), hypertension (14.3%), diarrhea (9.5%), tremor (9.5%), and diaphoresis (9.5%). The most frequently administered therapies included benzodiazepines (57.1%), fluids (38.1%), and antiemetics (19.1%).

Among the 183 exposure calls with a known outcome, significant associations were found between outcome severity for tianeptine-only exposures versus tianeptine with coexposures (p = 0.01) and between outcome severity and sex (p = 0.02). Persons reporting coexposure along with tianeptine were more likely to have major outcomes than those with tianeptine-only exposures. Men were more likely than women to have a moderate outcome. No differences were found between outcome severity and age group (<20, 21–40, 41–60, and ≥61 years) (p = 0.93).