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Experts estimate that in Germany, one in four women and one in eight men experience depression one or more times in their lifetime. According to estimates by the World Health Organization, more than 300 million people are affected worldwide, including in modern industrial and service companies.
"Although effective and well-tolerated drugs are available for moderate and severe depression, unfortunately, about one-third of patients do not respond to these drugs," says Professor Isabella Heuser, head of Charity's Department of Psychiatry and Psychotherapy. – Universitätsmedizin Berlin of Benjamin Franklin Campus.
Depression caused, for example, by stress, relationship problems, divorce or the loss of a close relative, is a disease that accompanies physical changes. Thus, besides depression, sleep problems, fatigue, apathy, lack of appetite, loss of libido and the feeling of being able to work "on autopilot", the symptoms of depression include changes in levels may, for example, lead to the failure of menstruation. But that's not all.
We still do not know what cause and what effect
"We now know that the immune system of some patients is activated, even if there is no infection by bacteria, viruses or fungi." Isabella Heuser and some colleagues suspect that she touches exactly one third of patients who do not benefit from conventional antidepressant treatment.
It is still unclear what the cause is and what is the effect: Is the immune system activated by stress and triggering depression? Or does depression release more and more stress hormones that stimulate the immune system? The stress response and the immune response are known to be closely related. "Although we can not yet demonstrate the pathophysiological cause chain: this does not mean that we can not try to calm the hyperactive immune system," Heuser explains, "with minocycline, a tried and well tolerated tetracycline antibiotic." "It works not only antibacterial, but also anti-inflammatory and neuroprotective, thus protects nerve cells and fibers.
Unlike most other antibiotics, minocycline can cross the blood-brain barrier that normally protects the brain from pathogens or substances that circulate in the blood. This is crucial in this case because the brain has its own immune system, which is also activated when the body releases inflammatory and anti-inflammatory messengers, called cytokines. "From animal studies, we know that experimentally depressed mice have activated immune cells in the brain and after minocycline their activity is significantly reduced," says Heuser. A Canadian study of 2017 showed the good anti-inflammatory effect of the antibiotic on the brains of multiple sclerosis patients. Pilot studies have also been conducted on depressive or bipolar subjects. They were also promising.
What happens in the brain when the immune system goes against the barricades?
The psychiatrist is currently conducting a multi-center, double-blind study of the efficacy of minocycline in the treatment of depression in 160 subjects. Neither the investigator nor the patient knows who will receive the active substance and who will receive the placebo. In addition to the Free University of Berlin, the teaching hospitals of Aachen, Erlangen, Frankfurt, Göttingen, Munich and Regensburg, as well as the Max Planck Institute of Psychiatry Munich are also involved. Minocycline has long been used successfully against acne and rheumatism and has few side effects.
What happens in the brain when its immune system is subjected to barricades? "In certain areas of the brain, such as the limbic system that regulates our emotions, cytokines affect the action of messengers such as dopamine, norepinephrine, and acetylcholine," says Isabella Heuser. "This leads to behavioral changes." Limbic system disorders, which are also responsible for the release of happiness hormones (endorphins), are thought to be the cause of various diseases, including post-traumatic stress disorder, autism, and depression.
People with a real infection – such as the flu – also show a change in behavior: they feel soft, have no energy, have little appetite, retire and are barely able to work. Symptoms that are very similar to those of depression, which argues in favor of the theory of a relationship between depression and the activated immune system.
The results are expected early 2020
Study participants receive a constant dose of minocycline for six weeks, then are interviewed once a week about their condition in detail. After six months, they will be ordered again. Before and after antibiotic therapy, they are bled and examined for all known cytokines.
"We hope to show in the end that subjects with these inflammatory markers actually responded positively to the antibiotic," explains Isabelle Heuser. In the ideal case, they even have a very specific pattern of cytokines. If the minocycline meets expectations and is soon approved as a drug against depression, this tendency in the blood of a patient – so hopes the professor – is in advance a definite indication of therapeutic success.
Interested parties can register for the outpatient minocycline study with Vera Clemens, doctor in charge of the study, until September 2019 (email: [email protected]). of). Participation is conditioned by the failure of two previous antidepressant treatment attempts with different medications. The results of the study are expected early in 2020.
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