Resistant depression: why antidepressants do not always work and what alternatives science offers in those cases

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Considered the evil of the 21st century, depression affects about 4.4% of the world's population and is the leading cause of disability, according to the World Health Organization (WHO). In a decade, between 2005 and 2015, the number of people with this disorder increased by 18.4% worldwide, according to the latest WHO report on the subject. In Brazil alone, 5.8% of the population suffers from the disease, the highest rate in the Latin American continent. Although there are several pharmacological therapies and effective psychological treatments for this disease, in a portion of those who suffer depression - between 10% and 30% - have little or no effect. These people have what is called treatment-resistant depression, also known as refractory depression. What is "smiling depression" and why is it more dangerous than the other types "This occurs when a patient, after following a treatment with two different classes of antidepressants for more than six weeks in therapeutic doses, does not present any improvement," explains psychiatrist Wagner Gattaz, coordinator of the Neurosciences Laboratory of the Institute of Psychiatry ( IPq) of the University of Sao Paulo (USP). According to the doctor, the causes are not yet fully known, just as those of depression itself are not known. On Mental Health Day, we tell you what this type of depression consists of. Individual variety One possible explanation is the great individual variability in the destination of the drug after taking it. "This variability begins in the stomach and intestine, which determine how much of the medicine will be absorbed and will pass into the bloodstream. Some people absorb more, which guarantees them a better result, and others less," he says. There are also individual differences when the medicine reaches the brain. "The goal of antidepressants is nerve connections, in which different neurotransmitters predominate, such as serotonin, norepinephrine and dopamine. But both the production of these neurotransmitters and the sensitivity of their receptors vary from person to person." Apart from that, there is individual variability in the speed with which drugs are metabolized in the liver. "What if I told you that depression also has its charm?": Wilfrido Vargas talks about a condition that has haunted him all his life about 70% of people metabolize these drugs at a normal rate. The remaining 30% can do it very quickly, without giving it time for the medicine to take effect; or slow, which causes the drug to accumulate in the body and cause a series of side effects. "We know that factors related to pharmacokinetics (the science that studies the path of medications in the human body from ingestion to excretion) and pharmacodynamics (the study of the mechanism of action of medications with their receptors) determine the differences in the response and reaction to antidepressants among people, "adds Gattaz. Antonio Geraldo da Silva, president of the Latin American Psychiatric Association (APAL) and superintendent of the Brazilian Psychiatric Association (BPA), highlights another hypothesis to explain resistance to depression treatments. "We have basically available the antidepressants' selective serotonin reuptake inhibitor ',' selective norepinephrine reuptake inhibitor ',' dual ',' dopaminergic ',' tricyclic ',' tetracyclic ',' monoamine oxidase inhibitors ',' melatoninergic 'and' lithium carbonate ', which is used as a mood stabilizer but also has antidepressant action. " "When the patient does not respond to any of them, alone or in combination, it may be because in his case the medication would need to act with some other brain substance that we do not know or identify," he explains. What may also compromise the outcome of treatment are associated with diseases, such as thyroid disorders, chronic pain and bipolar disorder, and the combined use of other medications. Treatment strategies Although resistant depression is a bit more difficult to treat, there are tools. One of them is the pharmacogenetic test, which performs a DNA analysis to see which medications are most suitable for each person and which ones they will have an intolerance. "This test increases the probability of getting the medication right, it gives us an orientation to adjust the dose," says Gattaz. It can be done by collecting saliva or oral mucosa, or a blood sample. What is dystonia and why could it be the reason you don't want to get up in the morning "Here (in Brazil) we do it through the blood. We observe the genes in the group of cytochrome P450 enzymes responsible for the metabolism of drugs in the liver, and we can identify a priori if the patient is an ultrafast or slow metabolizer," says the IPq-USP specialist, In addition, there are somatic therapies, which must be associated with drug therapies. One of them is transcranial magnetic stimulation (EMT), a non-invasive technique that stimulates the brain with magnetic waves by modulating neurotransmitters. To obtain a good result, 20 sessions are held, initially daily. "The application is done with the patient awake and from the session number ten you begin to see an improvement," says Gattaz. Another option is electroconvulsive therapy (ECT), which, through a low electrical current, induces seizures and, therefore, causes chemical changes in the brain. "This method causes depolarization of the neuronal membrane, opening channels of communication between neurons," says Silva, from ABP. The problem, however, is that this therapy is sometimes seen as a form of punishment. "However, it is safe and its therapeutic success has been highlighted by several studies," adds Silva. In ECT, the application is performed with the anaesthetized patient. They are held from 9 to 12 sessions, two or three times a week. "Some people show signs of improvement in the first session, but for the effect to be complete, all treatment must be done," says the doctor. It should be noted that both EMT and ECT are not indicated in all cases, and only the psychiatrist can assess the need individually. Another possible therapy is the use of a nasal spray of ketamine, a substance derived from anaesthetic ketamine. "It has ultra-fast action and good tolerance," says Gattaz. To get an idea, while the pills take between two and three weeks to work, this medication is effective within 24 hours after the first application. Its mechanism of action is different from traditional antidepressants. While traditional antidepressants increase pleasure-related neurotransmitters, the spray acts on glutamate, a molecule of the neural network, by stimulating areas of the brain that are linked to emotions. In the United States, this medication was approved in March this year by the Food and Drug Administration (FDA), the food and drug regulatory and regulatory body. There it is only administered under medical supervision.

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