Why is tianeptine uncomfortable at high doses

Are antidepressants addictive?

The findings question the use of SNRI in mood and anxiety disorders, Fava and colleagues conclude. The authors also demand that doctors add SSRIs and SNRIs to the list of drugs that can cause withdrawal symptoms after the end of treatment, as well as benzodiazepines, for example. In addition, the term »discontinuation syndrome« used in English trivializes the possible symptoms and should be replaced by »withdrawal syndrome«. Uwe Gonther, on the other hand, considers discussions about the term to be of secondary importance: "It would be a lot to gain if one accepted that sometimes severe and long-lasting symptoms occur after weaning."

Withdrawal is similar to that of benzodiazepines

In 2011, scientists from the Nordic Cochrane Center in Copenhagen also concluded that the withdrawal response to SSRIs was similar to that of benzodiazepines. It makes sense to view the symptoms with SSRIs (as with the benzodiazepines) as part of a dependency syndrome. The Danish researchers see the reason for the inequality of treatment in the fact that the definition of dependency in the classification systems for mental disorders has been changed. Since a revision of the DSM III revision in 1987, which took place shortly before the SSRI was launched on the market, several criteria must be met for this diagnosis, for example a strong desire for the substance or the neglect of interests. Previously, a development of tolerance or the presence of withdrawal symptoms were sufficient.

How do antidepressants work?

Selective serotonin reuptake inhibitors (SSRIs) increase the concentration of serotonin in the synaptic gap between nerve cells. The suspected mechanism of action is based on the hypothesis that a lack of serotonin in the brain is responsible for the development of depression. So people need a certain dose of this neurotransmitter in order to be in a good mood. Researchers came to this point in the late 1960s when they found a lower concentration of a breakdown product of serotonin in depressed patients. So far, however, the relationship between this substance and the severity of depression is unclear. In addition, the active ingredient tianeptine, for example, reduces the serotonin concentration in the synaptic gap and has nevertheless been approved for depression since 2012 because clinical studies have shown its effectiveness. Other antidepressants, on the other hand, do not affect serotonin levels at all - so the different drugs are not based on the same biochemical mechanism. Furthermore, although a diet low in tryptophan lowers the serotonin concentration, this does not trigger depression in healthy people. A diet rich in tryptophan also does not help depressed people. Tryptophan is found in many foods and the body uses it to make serotonin. Because of such contradicting findings, the serotonin hypothesis does not seem to do justice to the complexity of the disorder. The current German guidelines therefore state: »There is still a lack of clarity about the mechanisms by which the antidepressants work. It is therefore still not possible to predict reliably whether and when a certain patient will respond to a certain antidepressant. "

James Davies from the University of Roehampton in London and John Read from the University of East London also believe that the current guidelines underestimate the severity and duration of withdrawal from antidepressants. For their review article published in 2018, the two had analyzed the previous literature on withdrawal symptoms from antidepressants. More than half of the patients reported such symptoms. And almost every second person with withdrawal symptoms described them as serious. In addition, they often persisted for several weeks or even months.

It is assumed that there are differences between the individual antidepressants, but hardly any data exist. Tom Stockmann of University College London and his colleagues compared the withdrawal from SSRI with that of SNRI in 2018. To do this, they analyzed over 170 posts on a US Internet platform for those affected. The withdrawal symptoms persisted significantly longer with SSRIs averaging 90 weeks than with SNRIs with 50 weeks (almost a year). Urogenital or psychosexual complaints such as difficulty urinating or erectile dysfunction were more common with SSRIs than with SNRIs. In contrast, neurological problems such as "brain zaps" seem to occur more frequently with SNRIs. However, since the site is designed to help people with antidepressant withdrawal, it primarily attracts those who are severely affected. Therefore, the duration of the symptoms determined there cannot be transferred to all users of antidepressants. A similar problem with preselection may also exist in other studies mentioned. For example, when researchers put a questionnaire about their experiences with antidepressants online, it is entirely possible that primarily people who have or have had problems with the drug take part. Therefore, placebo-controlled clinical studies are urgently needed, in which neither the investigator nor the test person knows whether the latter is receiving the active ingredient. This is the only way to estimate how often antidepressants actually cause withdrawal symptoms.

With Tim, the diffuse symptoms did not go away after a few weeks. Like many of his fellow sufferers, he went looking for more information. He came across a lot of experience reports on the Internet - especially in the German-speaking ADFD forum. "The abbreviation is based on the former name Antidepressiva Forum Deutschland," explains a team member of the private initiative that is committed to the platform under the pseudonym Iris Heffmann. In the meantime, those affected and their relatives are also exchanging ideas about the side effects and withdrawal symptoms of other psychotropic drugs such as benzodiazepines.

Tim was shocked by the various complaints he read about there. The symptoms can affect all possible areas, such as perception, well-being, cognition, the cardiovascular, digestive or immune systems. The spectrum ranges from dizziness and nausea to sensitivity to touch, tension, sudden burning, tingling or itching of the skin, a feeling of cotton wool in the head and more. "Many also report fear, restlessness or despair," explains Heffmann. In her experience, the symptoms usually come on in bursts. In between there are always phases with less or no complaints. While some people could get off the medication without any major problems, others would suffer from the effects for months or years. In particular, the latter group is only inadequately recognized by the treating physicians, according to Heffmann's assessment.