While serotonin reuptake inhibitors can be effective antidepressants, so can drugs which cause the brain to reuptake more serotonin. This reuptake enhancement decreases the amount of serotonin-fueled neurotransmissions. Yet instead of making the situation worse, in many cases SSREs are more effective antidepressants than SSRIs. A 2002 study found the SSRE tianeptine (sold in Europe as Stablon™ and Coaxil™) worked as well as fluoxetine, paroxetine (Paxil™) and sertraline (Zoloft™). A 60-day Indian study of 320 outpatients with major depression given tianeptine found that more than half showed greater than 50% improvement in the Hamilton depression rating scale (HDRS): only 23 patients (7.2%) reported side effects, none serious enough to cause the patient to withdraw from the study.
While their efficacy has been proven in numerous studies, we still do not know exactly how SSREs work. Some research suggests they may improve the brain's ability to respond to stress and limit the damage frequently seen in patients suffering from long-term depression: tianeptine appears to have a positive effect not only on the emotional affect of depressed patients but also on their cognitive ability. Other clinicians theorize that both SSRIs and SSREs result in less serotonin being available to neurons: SSREs accomplish this through increased reuptake while SSRIs cause receptors on the neurons to become less sensitive in response to greater serotonin availability. Whatever their mechanism of action, it is clear that SSREs call into question many commonly accepted ideas about the workings of antidepressant medications.
SSREs may have a greater potential for abuse than other antidepressants, since many patients report amphetamine-like stimulation. A 2004 study of 203 amineptine (Survector™) patients in Kuwait found that many were using it to relieve fatigue and induce feelings of well-being. When told to discontinue their amineptine use 93% of the patients reported a strong desire to continue taking the drug, and only 46 of the patients were able to discontinue their usage without resorting to black market amineptine or other drugs. A Turkish medical journal reported a case of a 34 year-old patient with a history of drug abuse who was taking 3,000 mg of tianeptine a day (the usual dose is 37.5 mg) to achieve euphoria and increased physical energy. Paradoxically, heroin addicts in Russia and Armenia have taken to shooting up large quantities of tianeptine pills to get an opiate-like high. (This is exceedingly dangerous as the injections are rarely filtered properly and the sludge from the pills frequently results in thrombosis, abscesses and tissue necrosis).
Currently no SSREs are available in American or British pharmacies. Amineptine production has been discontinued in most markets due to issues with liver toxicity and severe acne in some users. While tianeptine is still prescribed as an antidepressant and anti-anxiety medication in Europe and Latin America, there is little chance it will be made available to American patients. Tianeptine was developed in the mid-1960s and its patent has long since expired. Any company wishing to bring it to the American market would have to submit to rigorous and expensive safety tests to meet FDA standards: once those tests were passed, any company wishing to market a generic version could do so legally. There have been some tests suggesting tianeptine is effective in the treatment of asthma, fibromyalgia, attention deficit disorder and irritable bowel syndrome. Should it be approved for any of those conditions, American physicians would be able to write "off label" prescriptions for depressed patients.