Mental Health: Refractory Depression: What to Do When Antidepressants Don’t Work

Mental Health: Refractory Depression: What to Do When Antidepressants Don’t Work

Refractory depression, also called resistant or major depressive disorder, is characterized by chronic, long-term symptoms that do not respond adequately to standard treatments, such as medication and psychotherapy.

Psychiatrist André Brunoni, associate professor and lecturer at the Department of Psychiatry at the Faculty of Medicine of the University of São Paulo (FMUSP) and coordinator of the Neuromodulation Service at IPq (Institute of Psychiatry at the Hospital das Clínicas at FMUSP) explains that the cause The exact cause of refractory depression is not known, but it is believed to be a combination of biological and environmental factors, including genetics, lifestyle and stress.

“It is important to note that refractory depression is not a sign of weakness or lack of willpower, but rather an indication that regular treatments are not working and more intensive therapies may be needed,” he says.

Symptoms include persistent feelings of sadness and hopelessness, loss of interest in activities that were once pleasurable, changes in appetite or sleep patterns, difficulty focusing or making decisions, fatigue, low self-esteem, and thoughts of suicide or death.

Treatments for refractory depression can vary depending on the individual and the severity of their symptoms. They usually involve a combination of medications such as antidepressants, psychotherapy, and lifestyle changes.

To treat resistant depressive disorder, psychiatrists usually prescribe different types of antidepressants, for a certain period of time, in order to verify which one has the best effect on the patient.

In some cases, however, more intensive treatments such as electroconvulsive resection (ECT), neuromodulation and the use of ketamine may be recommended.


Transcranial Magnetic Stimulation (TMS), also called neuromodulation, is the leading medical treatment in the non-invasive neuromodulation class. Through EMT, magnetic pulses reach the neurons, stimulating or decreasing their activity, according to the needs of each case.

The stimulus goes beyond the cranial structure until it reaches the cerebral cortex and reaches the neurons, improving depressive symptoms.

These low frequency pulses (usually at 1 hertz) will inhibit activity in that region of the brain. High frequency ones (generally at 10 hertz) will stimulate its operation.

An EMT session usually lasts 15 to 20 minutes. In the office, the physician places a coil, connected to the EMT device, which generates electromagnetic pulses over the head of the patient, who is seated in an armchair.

The person remains conscious and feels only mild tingling at the site of stimulation. After the session, the patient can get up and go normally without any restrictions.

“Neuromodulation and electroconvulsive therapy are two different types of treatments used to treat certain mental health conditions. While ECT is used to treat severe depression, neuromodulation is a newer form of treatment that has fewer side effects,” says Brunoni.

The first magnetic stimulation device appeared in the 1970s, in the United Kingdom, to restore brain functioning. The technique was improved by physician Anthony Baker in the 1980s. In Brazil, TMS was regulated in 2012 by the CFM (Conselho Federal de Medicina) as a medical procedure for the treatment of psychiatric illnesses.

electroconvulsive therapy

Electroconvulsive therapy (ECT), popularly known as electroshock, was developed in the 1930s to treat psychiatric disorders. The technique is performed in a hospital environment, under general anesthesia, and induces a seizure by means of an electrical discharge.

While in electroconvulsive therapy there may be memory loss, in transcranial magnetic stimulation this aspect can be improved, depending on the point stimulated in the session.

The CFM (Conselho Federal de Medicina) regulates the use of electroconvulsive therapy since 2002 in the country. The method is indicated in cases of severe depression, risk of imminent suicide, bipolar disorder, catatonic form of schizophrenia, cases in which the patient does not respond to medications or cannot ingest them.

ECT is the most effective and fast-acting treatment for severe depression. Because it has side effects, such as memory loss, the benefits need to be evaluated by a psychiatrist.


Ketamine, also called ketamine, is a drug with an anesthetic effect. The substance was discovered in the 1960s, but it was only in the last 20 years that doctors began to research its application, in low doses, in the treatment of resistant depression.

The intravenous ketamine session is performed in a controlled and supervised medical environment. “The patient is monitored and monitored to ensure the safety of the procedure. He is connected to the intravenous infusion equipment, which contains ketamine, and the drug is slowly released into the body over 40 to 60 minutes”, reports Brunoni.

After the procedure, the patient should avoid driving vehicles or performing activities that require concentration.

Esketamine is the intranasal form of ketamine. “The patient inhales the medication and remains monitored for 1 to 2 hours to observe side effects. It should also be done in a supervised environment”, says Brunoni.


The CVV (Centro de Valorização da Vida) was founded in São Paulo in 1962. It is a non-profit civil association recognized as a Federal Public Utility since 1973.

The center provides a voluntary and free service of emotional support and suicide prevention for all people who want and need to talk, under total secrecy and anonymity.

The telephone number 188 started operating in Rio Grande do Sul and, in September 2017, began its expansion to all of Brazil, being concluded in June 2018, reaching all states.

Contacts with the CVV are made by telephone through the number 188 (24-hour service and no call costs), in person (at the 110 service points throughout the country) or through the website, by chat and email. In these channels, more than 3 million calls are made annually by approximately 4,000 volunteers across the country.

In addition to services, the CVV also maintains the Francisca Julia Hospital, which serves people with mental disorders and chemical dependency in São José dos Campos, in the interior of São Paulo.


By phone

Call 188 anytime. The service is 24 hours a day, free of charge and guarantees anonymity and absolute secrecy.

By email

Go to, fill in the fields with your name, email and message, and a volunteer will respond as soon as possible

by chat

To start the conversation, visit and click on the indicated link. The service takes place from Monday to Thursday, from 9 am to 1 am, on Fridays, from 3 pm to 11 pm, on Saturdays, from 4 pm to 1 am, and on Sundays, from 5 pm to 1 am

Personal attendance

To speak in person with a CVV volunteer at service stations, visit and look for the nearest address. It is also possible to send a letter, which will be answered by a volunteer

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