Antidepressants ineffective in some people?

Antidepressants ineffective in some people due to high numbers of serotonin receptors? US researchers have discovered a possible reason for the ineffectiveness of antidepressants in mice in a brain region. They found many serotonin receptors there, which could probably inhibit the effect of an artificial increase in the serotonin level by drugs.

Researchers led by Jesse Richardson-Jones from Columbia University in New York published the findings in the current issue of the US journal Neuron (Volume 65 Issue 1)..

In the past, it has long been assumed that drug-treated people who responded poorly to the antidepressants could have many of the serotonin receptors mentioned above. However, there was always a discrepancy between acceptance and traceability.

Richardson-Jones and his colleagues were now in a position to make a definitive statement, because they genetically engineered the mice in their attempt so that they were able to specifically increase the number of said receptors, or reduce. They were able to determine that the experimental animals with an above-average number of autoreceptors hardly or not at all responded to the drugs of the group of Selective Serotonin Reuptake Inhibitors (SSRIs). If the researchers reduced the number of recorders, they could register an effect.

Background of the high media attention of the results is, among other things, the smoldering discussion for years about the role of ONE substance (in this case, serotonin) and, of course, especially the gift and effect of a drug in depression play.

Serotonin and depression - the monoamine theory
In case of depression, sufferers are often affected by mood, sleeping patterns and emotional processes. These are all features that are heavily influenced by serotonin. Therefore, from a biochemical point of view, it seems conclusive that the serotonin has something to do with it in the organism of those affected.

This view was probably made in the 1950s, when a hypertension agent (reserpine) was considered the trigger of depression and was then claimed that it would cause a lack of said serotonin and another hormone (norepinephrine). Since both belong to the group of so-called monoamines, this thesis was called the "monoamine theory".

The Selective Serotonin Reuptake Inhibitors (SSRIs) drugs increase, for example with the drug paroxetine, the serotonin concentration in the synaptic cleft - this is the space between the end of a nerve cell and the subsequent cell to which the stimulus is to be transmitted (usually muscle or other nerve cells) - because they have a strong inhibitory effect on the reuptake of serotonin, thus ultimately preventing the deactivation of the neurotransmitter.

But there are also other treatment models:The active ingredient Tianeptin,in the drug Stablon® of the French pharmaceutical company Les Laboratories Serviers is a so-called serotonin reuptake enhancer (SSRE). He does exactly the opposite of the SSRIs at the synaptic cleft. He accelerates the reuptake of serotonin. And he should also antidepressant and anxiolytic with fewer side effects than SSRI. In Germany, the drug for the treatment of depressive disorders is not approved and not available.

Other theories of depression genesis and treatment
As mentioned earlier, the neurotransmitter norepinephrine is also thought to be linked to depression, and that the current remedy may also affect norepinephrine and thus depression. And also the effect of dopamine is discussed in the context of depression.

It does not seem to be very difficult, especially from a biochemical point of view, to make unambiguous statements in such complex mechanisms of action as those of neurotransmitters without recognizing and (in the treatment of) observing relationships. Because just as a neurotransmitter has several influencing mechanisms and sites in our organism, this also applies to a drug with its active ingredients.

Currently, researchers came to Dr. James E. Gangwisch from the Columbia University Medical Center, New York, on findings that support the thesis that too little sleep, especially among adolescents, could lead to depression and suicidal thoughts.

Washington State University researchers in Richland, Washington reported that women taking vitamin D also had an effect on depression, according to the Food Consumer. The psychologist Prof. Irving Kirsch of the University of Hull in England stated in 2002 that placebos achieve an average of 82% of the effects of antidepressants and even in his latest book "The emperor's new drugs: Exploding the anti-depressant myth" even believes that the The thesis that depression is caused by a chemical imbalance in the mind is simply wrong.

Richardson-Jones and colleagues now want to prove these mechanisms in humans. Even before the beginning of a drug treatment, it should be possible to test for the presence of many autoreceptors and possibly to block them with inhibitors. But one important point is that personal fate and the psychotherapeutic approach are left out in a purely biochemical view. (Thorsten Fischer, Naturopath Osteopathy 15.01.2010)

additional Information

1st book by Irving Kirsch:
Cherry, Irving (2009). The Emperor's New Drugs: Exploding the Antidepressant Myth. London: The Bodley Head