As part of its public health mission, the Food and Drug Administation (FDA) has been monitoring for adverse effects from opioids and opioid-like substances for years. Two recent examples of concern are loperamide and kratom.
Loperamide, an over-the-counter antidiarrheal and a peripherally acting opioid, has been used in higher than recommended doses, resulting in serious heart problems or death. Kratom, also known as Mitragyna speciosa, has opioid-like properties that expose users to the risks of addiction, abuse and dependence. More recently, tianeptine has emerged as another substance being sought for its opioid-like qualities. Although it is approved in several other countries to treat depression and anxiety, it is not approved in the U.S.
The FDA is seeing signals that suggest tianeptine use may be increasing in the United States and that a growing number of people are experiencing associated significant adverse events. Tianeptine is an atypical antidepressant. Tianeptine is structurally similar to tricyclic antidepressants. However, among other actions, the drug activates the mu and delta opioid receptors and may increase dopamine release. This mechanism is hypothesized to influence tianeptine’s antidepressant qualities but could also create a euphoric effect similar to other drugs with potential for abuse.
Several countries that initially approved tianeptine have since either removed it from sale or restricted its use due to concerns about risks for abuse. In the U.S., in response to a series of tianeptine overdoses, Michigan recently placed the drug on its list of controlled dangerous substances. Similar legislation is being considered in Alabama, Minnesota and New York.
Although it is not an FDA-approved product, tianeptine is sold in the U.S. via online merchants and in convenience stores, and it is typically supplied in capsule, tablet or powder forms. It is among a variety of substances being marketed as a “nootropic” or “smart drugs” — dietary supplements that purportedly have cognitive-enhancing qualities.
Based on findings from the FDA’s Center For Food Safety and Nutrition (CFSAN), the agency sent warning letters to two companies illegally marketing tianeptine-containing products labeled as dietary supplements claiming to treat opioid use disorder, pain and anxiety, among other unlawful and unproven claims. Consistent with U.S. Centers of Disease Congtrol (CDC) findings, FDA has found that tianeptine use in the U.S. may be increasing and is associated with death and other serious adverse events that may be attributed to its opioid-like properties.
The opioid crisis continues to evolve, and people continue to seek opioid-like effects from the misuse of novel agents. The FDA advises health care professionals to be aware that products containing tianeptine have not been evaluated by FDA for either efficacy or safety, and to consider the possibility of tianeptine use when evaluating a patient with clinical evidence of opioid use. FDA will continue to monitor these trends and communicate to practitioners.