An antidepressant with a unique proposed mechanism of action, Tianeptine (Stablon is one trade name) has been used with some limited success globally for years. The novel mechanism of this medication involves some activation of opioid receptors and tracts associated with the mesolimbic dopamine pathway in the brain. This fact led to some concerns in the U.S. about potential for abuse, apparently hobbling its potential for clinical success in this area. This same opioid receptor activity that worried some physicians in the U.S. , according to proponents of this drug, could actually be the reason why it is effective for some patients. The area of the brain that appears to be defective or underactive in individuals susceptible to addiction could potentially be "turned on" safely with this medication, leading to more enjoyment of positive activities and thus improving depression symptoms. This sub-type of depression, or more accurately this return to an anhedonic pre-addiction state, likely represents a return to baseline for individuals who experienced underactivity of reward pathways as a result of genetic variants. This gene-based underactivity may be independent from the theorized brain changes that can directly result from substance use itself.
The argument for Tianeptine could be made that patients with a history of addiction, particularly opioid dependence, often experience depression that is difficult to treat after achieving sustained sobriety and that a controlled stimulation of these circuits with Tianeptine could improve mood and potentially help prevent relapse rather than trigger it. Similar rationale for avoiding psychostimulant medications for patients on Buprenorphine has been largely debunked, with patient outcomes improving with appropriate ADHD treatment rather than patients experiencing relapse due to the activation of the reward pathway by a different substance.
If a stable patient in recovery, or a patient with a strong family history of substance abuse, experiences depression that does not respond to standard antidepressants or other evidence-based therapies such as TMS, cardiovascular exercise, CBT, and light box therapy, the argument could be made to try Tianeptine. In the aftermath of the devastation caused by the current opioid epidemic, the time is at hand to think outside the box when it comes to the options for treatment resistant depression.