Ketamine treats resistant depression and suicidal ideation – 02/03/2023 – Mental Health

In 2019, physician Carolina (fictitious name), 49, spent eight months at home almost never getting out of bed. She faced severe depression and stopped working.

After trying different types of medication against the disorder and not seeing any improvement, Carolina’s psychiatrist recommended that she undergo ketamine infusion sessions.

The substance has an anesthetic effect and has been used since the 1960s to keep patients sedated during surgical procedures.

At the end of the 1990s, the drug began to be studied as an alternative to treat resistant depression —cases like Carolina’s, when the use of antidepressants fails to get the person out of a serious condition of the disease.

“In the brain, classic antidepressants modulate the monoaminergic systems —noradrenaline, serotonin and dopamine. Ketamine’s mechanisms of action involve the modulation of the glutamatergic system”, explains psychiatrist Leandro Valiengo, coordinator of the Interdisciplinary Neuromodulation Service and the Ketamine Service from IPq HC-FMUSP (Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine, University of São Paulo).

The hypothesis that depression is caused by a lack of serotonin or a chemical imbalance in the brain was dominant in the medical literature for many years, but it is not the only one, says anesthetist Tiago Gil, founder of the Ketamine Center in São Paulo.

“One of these hypotheses is the glutamatergic, or excitatory neuron, which explains depression by the hyperactivation of some areas of the brain that occurs by the action of the neurotransmitter glutamate”, says Gil.

This was the suspicion investigated in the late 1990s by physician John Krystal, a professor at Yale University, in the United States. He applied ketamine to mice, at doses lower than those used in anesthesia, to block the action of glutamate and evaluate the antidepressant response. In the 2000s, Krystal and other researchers published the first proof-of-concept work with positive results of ketamine against depression.

The first clinic to offer ketamine infusions to treat the disorder appeared in 2014 in the United States. In Brazil, the first such establishment appeared in 2016.

The use of the substance against depression is off-label, that is, it is not in the leaflet. The indication should always come from a psychiatrist, who will also monitor the patient’s treatment and evolution.

Ketamine acts on the brain in such a way that, in some cases, it can show antidepressant effects within hours, says Valiengo.

That’s what happened to Carolina, who started to feel better 24 hours after the first application. After three sessions, she was able to return to work.

Currently, the doctor repeats the procedure once a month as maintenance.

The psychiatrist points out that ketamine is especially indicated in cases of suicidal ideation. “A recent study with 156 participants, published in the medical journal “The BMJ”, demonstrated a decrease of more than 63% in suicidal ideation within three days after the application of a dose of ketamine against only 30% reduction in the placebo group. “

The treatment, however, is contraindicated for patients with psychotic or chemically dependent conditions. Some clinical conditions, such as arterial hypertension, heart or lung disease, need to be controlled before applications. Therefore, some tests may be requested by the responsible physician.

Tiago Gil clarifies that the sessions must always be accompanied by an anesthetist, who will check the heartbeat, oxygenation and blood pressure, as in surgeries.

During the procedure, the person will feel the psychotomimetic effects of the substance, which is considered a psychedelic, like the sensation of being outside one’s own body. “It is important that the patient is accompanied by someone they trust, such as a family member or even a psychologist”, says Gil.

The application is carried out in an outpatient room, equipped with hospital equipment, headphones to listen to music and low lighting that provides relaxation. In addition to the patient and doctor, the companion can stay in the space.

During and after administration of ketamine, nausea, headache and blurred vision may occur, but these effects usually last for a maximum of one hour. It is contraindicated to drive or operate machines on the same day as the infusion.

Six sessions are usually indicated over a month to assess the response against depression symptoms. Depending on the result, more infusions can be performed over a longer period of time, which will be defined by the doctor.

Leandro Valiengo explains that the treatment is monitored by a psychiatrist, who will analyze the need for the patient to continue taking oral medications, such as antidepressants and mood moderators.

In addition to the intravenous form, ketamine can be administered through a nasal spray. Both are performed in a hospital environment.

Each intravenous application costs an average of R$ 2,000. The spray costs R$ 2,500 each bottle, but two or three bottles are usually used in a session.

The treatment is not yet offered by the SUS (Unified Health System).

Valiengo says that, if the patient does not present improvement in the depressive condition after the use of ketamine, there are other treatments that can be tested, such as neuromodulation or Transcranial Magnetic Stimulation (TMS) and electroconvulsive therapy (ECT).

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