Using the Antidepressant Tianeptine to Manage Chronic Pain

Management of neuropathic pain (that results from a damaged or malfunctioning nervous system) has been particularly challenging as currently prescribed drugs, such as anticonvulsants and antidepressants can have severe adverse effects, are not well-tolerated, take a longer time to work and only help a subset of patients. 

In a new study investigators report that the atypical antidepressant tianeptine potentially provides rapid and lasting pain relief with a low risk of addiction.

Researchers used experimental models to investigate the persistent mechanical allodynia that is associated with damaged sciatic nerve, comparing the therapeutic profiles of tianeptine to that of the antidepressant desipramine.

To better understand the mechanisms underlying the drug’s effects, the investigators used RNA sequencing, to monitor gene expression changes in the nucleus accumbens, a brain region involved in motivation, addiction, and pain perception to identify pain-related genes that tianeptine treatment counteracts.

The results showed that tianeptine had profound pain-relieving properties that lasted well after the drug was no longer present, which suggested it was the drug that affected the expression of genes that were critical for the maintenance of pain symptoms. The researchers also found that tianeptine started working more quickly than other antidepressants.

“Several studies have shown that the abuse potential of tianeptine is substantially lower than other currently abused opioids such as oxycodone. Furthermore, based on prior studies, tianeptine does not appear to cause tolerance, so the dose does not need to be increased drastically over time as we see with opioids, which contributes to physical dependency and addiction,” said Zachariou and Alex Serafini, PhD. “The data from this study contributes to a much larger set of data supporting the use of this drug for conditions such as chronic pain.”


Randal A. Serafini, Molly Estill, Elizabeth A. Pekarskaya, Farhana Sakloth, Li Shen, Jonathan A. Javitch, Venetia Zachariou. Tianeptine promotes lasting antiallodynic effects in a mouse model of neuropathic pain. Neuropsychopharmacology, 2023; DOI: 10.1038/s41386-023-01645-w

Boston University School of Medicine. “Researchers use the antidepressant tianeptine to manage chronic pain: This study contributes to a large set of data supporting the use of tianeptine for chronic pain.” ScienceDaily. ScienceDaily, 24 July 2023. <>.

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