In the history of drugs were those few who were enthusiastic acceptance as the white-green capsule contains fluoxetine hydrochloride, a chemical known by the brand name Prozac (Ladose). In 1988, one year after approval by the Food and Drug Administration (FDA ), U.S. 2,469,000 issued prescriptions for Prozac. In 2002 rose to over 33 million. In 2008, antidepressants were in third place among the most prescribed drugs in the United States. Arriving in 2012, the same antidepressants that had caused so much excitement, were the black sheep of modern psychopharmacology, and overestimated ypersyntagografimena formulations, typical of a culture that looks fast solution to complex mental health problems.
In fact the same principles on which these drugs work, have been questioned.
The nerve cells, neurons, communicate through chemical signals called neurotransmitters which can have different forms: as serotonin, dopamine or norepinephrine. For decades, the prevailing theory was that antidepressants worked by increasing serotonin levels. They believed that the brains of people suffering from depression serotonin signal somehow been impaired due to chemical imbalance in neurotransmitters. And how Prozac (Ladose) and Paxil (Seroxat) could increase these levels between nerve cells by enhancing these signals - dynamonontas as a speaker to communicate between cells. However this theory has been widely criticized.
But it has actually surpassed the serotonin hypothesis of depression?
The results of recent surveys have confirmed that in fact the role of serotonin remains crucial for the disposal even though the mechanism of action is more impressive than we can ever imagine. To the Prozac Paxil and Zoloft may not be the miracle drugs we thought before, but have helped us to understand what depression is and how to treat it.
The modern understanding of the relationship between depression and chemicals in the brain was born almost by accident in the middle of last century. In the fall of 1951 the doctors of Sea View Hospital in Staten Island who used to treat TB patients a new drug, the iproniazidi, noticed a sudden change in mood and behavior of their patients. The ward, usually filled with dark and silent patients seemed apathetic and dying "was illuminated by happy faces of men and women" as a features reporter wrote after a visit to the hospital.
When Life magazine sent a photographer to the hospital, in relative research, patients were not stuck in their beds, but they played cards and danced in the aisles.few hundred kilometers south of the hospital patients Dukes lived a completely opposite experience. In 1954 he was prescribed to a woman 28 years Rauxidin (reserpine) to regulate blood pressure. After some months he returned to hospital complaining crying spells, drowsiness and lethargy. He felt useless, hopeless and full of guilt. A few months later, that empty feeling had become aggressive. This sense of misery as they remained until the patients stopped taking the drug. In another hospital where a patient was administered the same drug attempted suicide. Many people admitted to psychiatric hospitals and underwent electroshock to reduce symptoms.
Psychiatrists and pharmacologists have shown interest in these strange occurrences. They wondered how can two seemingly unrelated drugs, to cause such profound and adverse effect on mood. It was about that time where scientists discovered that the brain was "immersed" in a liquid chemicals. At the beginning of the century began to wonder how nerve cells communicate with each other. In the late 60's had now been shown that signals between neurons were transferred through several chemicals including the neurotransmitter serotonin. Scientists wondered if it was possible iproniazidi reserpine and altering levels of a neurotransmitter, changing the signals inside brain and thus the mood. It was exactly what was happening. The reserpine to cause a feeling of sadness, greatly reduce the concentration of serotonin and other neurotransmitters by which tied closely.
The drugs that caused the IRS as iproniazidi instead caused an increase in the concentration of serotonin. These discoveries led the first psychiatrists to formulate a new hypothesis for the cause and treatment of depression - was the result of a chemical imbalance of neurotransmitters: in normal brain serotonin traveled forth - forth between neurons maintaining a balance of mind while this does not happen in the brain of those suffering from depression. The writer Andrew Solomon described the depression as "loss of love." Doctors Hospital Duke had observed in real time the occurrence of this loss in their patients: decreased progressively love for their own self (guilt, shame, suicidal), love for others (accountability, aggression) and end of the very need for love (lethargy, introversion, apathy). But according to scientists all these were only the outward symptoms of malfunctioning neurotransmitters. The loss was the loss of love, chemicals.
This theory was confirmed with the discovery of new specific drugs that cause an increase in the concentration of serotonin. The first of these, Zimelidine (Normud) created by a Swedish researcher, the Arvid Carlsson. Following the example of the pharmacologist focused their efforts and use available resources to research drugs that enhance serotonin concentration, and thus were born in quick succession all new "giants" in the world of antidepressants. The Prozac was established in 1974, appeared in 1975, Paxil and Zoloft The 1977 (the trade name given some years later).
But to understand whether the absence of serotonin causes depression we need to know if the brains of people suffering from this disease, the levels of serotonin or serotonin metabolites (derived from the decomposition of) is actually lower. In 1975 a group of pathologists conducted autopsies on some depressed patients to make measurements. The preliminary findings seemed to confirm the theory: the depressed patients tended to have lower levels of serotonin. But in 1987 some Scandinavian researchers repeated the experiment with new measurement tools and found that in depressed patients, serotonin levels were higher. New experiments did other than to confirm that opposition. According to a test depressed patients had lower levels of serotonin, while according to other higher, for others there was no difference.
What would happen if the reverse experiment conducted?
In 1994 a volunteer group of McGill University in Montreal was a mixture of chemicals that lower levels of serotonin. Doctors noticed changes in their mood and reduced levels. Even when serotonin no longer existed at all, most people did not show significant changes in mood. At first glance these studies make us think that there is no relationship between serotonin and depression. But the experiment showed a McGill important fact: the lowering of serotonin did not produce any effect in healthy volunteers when they did not suffer from depression, and produced impressive results in people who had family history of depression. These people when serotonin levels decreased significantly worsened the mood. An earlier version of this experiment, conducted at Yale in 1990, was more alarming results. When patients suffering from depression and akoulouthousan types of therapy with drugs like Prozac were taking a mixture of substances that lower levels of serotonin often fell into deep depression. Other experiments showed that although not all patients with depression had lower levels of serotonin, for those who were suicidal, it sure was.
In the late 80's were some studies to verify the effects of Prozac to depressed people. It was found that compared with placebo the drug reduces symptoms of depression. Usually the diagnosis of depression become a standard ladder using symptoms. Altogether some patients experienced significant improvement of clinical, even if the results were usually very small and change from test to test. In real life, even these small changes could be very important: the reduction of anxiety, of guilt and the end of suicide. For other patients but the changes were marginal.
Perhaps the most important element that emerged from these test was the most subjective: 74% of patients say they feel better than when he was taking antidepressants.
In the late 80's, a neurologist named Fred Cage became interested in an issue that initially seemed far away with the problem of depression: Can an adult human brain produce new brain cells?
At that time, neurobiologists were convinced that an adult brain development and there was not born any more new nerve cells, that when the neural circuits created once during childhood remained stable and unchanged. But ifthe new neurons replace the old, memories should not be lost?
The Cage and other scientists have reviewed old findings and discovered that in fact in mice, rats and adult human beings form new neurons, but only in two specific areas of the brain: the olfactory bulb, where smells are recorded, and the hippocampus, which controls the instrument memory and that is functionally connected areas of the brain that control emotions.
To find out if there is any relationship between emotions and the birth of neurons in the hippocampus Cage and his colleagues began studying the rats under conditions of stress. When the mice subjected to chronic stress, either because their environment changes suddenly or because their beds are moved, they show symptoms of anxiety or apathy and become less active, all items are identified with depression in humans. Cage's team discovered that these mice to produce nerve cells in the hippocampus decreased. It seemed that was exactly the opposite. When the mice were placed in an environment with more stimuli that usually contained mazes, material for building the nest and become active play and active. By investigating more and learn faster searching pleasure. The stimuli practically functioned as antidepressants. When Cage examined the brains of these mice that received more stimulation, she realized that most were born hippocampal neurons.
At Columbia University, another scientist Rene Hen impressed by his studies with Cage and his colleagues began to investigate the relationship between Prozac and development of neurons. In mice o formation of new neurons requires two to three weeks, almost the same amount of time it takes to start antidepressant medication have an effect. Was possible the effects of Prozac and Paxil have been linked with the development of neurons and not only on concentration Serotonin?
The Hen began granting Prozac in the guinea pigs. After some days the behavior changed: the anxiety symptoms decreased and the animals become more active. searching for food in different places and have adopted new behaviors immediately. The new neurons in the hippocampus appeared at the same point that was noticed by Cage's own experiments. But when the Hen blocked the creation of neurons in the hippocampus, the tendency of peiramatozon be more active disappeared. In other words, the positive effects of the drug depended on the birth of nerve cells in the hippocampus.
In 2011 the Hen and colleagues have repeated this experiment, this time a group of monkeys. In monkeys, chronic stress creates symptoms similar to depression in humans. Even more than the mice, monkeys under stress lose interest for every pleasure and become apathetic. When measured the creation of neurons in the hippocampus of these animals, the Hen found that they were reduced. When monkeys instead granted an antidepressant, found that symptoms of depression decreased and that the neurons began to arise again. Blocking the development of nerve cells in Prozac was not working anymore.
The experimental results of Hen have important implications for psychiatry and psychology. Antidepressants such as Prozac and Zoloft, according to the Hen may temporarily raise levels of serotonin in the brain but the effect is visible only when new neurons are born .
Depression is a complex disease that can have different forms and causes. As demonstrated by clinical studies, only a fraction of patients suffering from severe depression responds to treatment with antidepressants that enhance the concentration of serotonin. Different reactions to drugs may also be due to biological differences in "paths". In some people could be involved in the different neurotransmitters serotonin. In other changes in the brain could be caused by biological factors other than neurotransmitters. And finally some of the chemical and biological agents could not be identifiable. For example, the depression associated with Parkinson's disease seems to have little to do with serotonin. The postpartum depression is a syndrome so special so it is difficult to imagine how the neurotransmitters or the birth of neurons in the hippocampus may play a decisive role in this. The new theories also explain why most of the psychotherapy work with some patients and not others, and why talking to a therapist and taking antidepressants also can have better results.
To study the unknown universe of mood and emotions our resources are few. We just want to combine chemicals and energize electrical circuits, implicitly hoping to understand the structure and functioning of the brain through the results. With time, these new theories of depression could very likely lead to the creation of new antidepressants. These medications will make Prozac and Paxil, to look outdated. Current antidepressants should not be considered medical conquest but technological breakthroughs, and these technology breakthroughs have allowed us to begin to understand something about our brains and biology this mysterious disease that affects humans.
Source:
Siddhartha Mukherjee
http://www.nytimes.com/
http://www.internazionale.it/
Internazionale, 26 Giugno/5Luglio 2012, N.95
Pictures, Benoit Paille
