In March 2019, the US Food and Drug Administration (FDA) approved the use of ketamine for the treatment of depression. This drug, which was released in the form of a nasal spray, was previously used for sedative purposes. Ketamine therapy is considered the most important development in the treatment of major depression in recent years.
The activity of neurons in our brain creates our emotions and thoughts. Neurons transmit signals electrically, but the connection between two neurons is chemical. At the synapse, which is the connection between one neuron and another, the stimulus is carried by chemical molecules. Chemicals released from the first neuron can have the effect of facilitating or complicating the stimulation of the second neuron. Neurotransmitter to chemical molecules used for this purposeis called. The neurotransmitters most commonly found in the brain are glutamate and GABA. Both are present in about half of the connections in the brain. Glutamate is a stimulant. GABA, on the other hand, has a suppressive (inhibitory) effect. There are also other neurotransmitters such as dopamine, serotonin, norepinephrine. These are some of the neurotransmitters known to influence our behavior. In fact, around 200 neurotransmitters have been discovered in our brain so far.
What Causes Depression?
Medicines that affect the brain often mimic, potentiate, or suppress natural neurotransmitters. Much of the knowledge about the behavioral roles of neurotransmitters has been learned from observing the effects of psychoactive drugs interacting with them. This is also the case with depression. In fact, we cannot say that we know exactly what depression is at the neural level. Because it is a disease that manifests itself in different ways in different people. As in many psychiatric problems, the disease is tried to be understood by observing the behaviors. Low mood, fatigue, mental fog, suicidal ideation are some of the symptoms of depression. In the 1960s, scientists noticed that drugs that alter the level of serotonin in the brain cause psychological side effects. Those who reduce serotonin led to depressive symptoms. Drugs that increase serotonin alleviated the symptoms of depression. In the light of these observations, the serotonin hypothesis was formed. Accordingly, depression is associated with a decrease in serotonin levels.
SSRIs (prozac, cipram, lustral, etc.) are selective serotonin reuptake inhibitor drugs. They were developed to treat depression by increasing serotonin activity. However, low serotonin does not fully explain depression. The levels of many other neurotransmitters also change in patients with depression. Therefore, it may not be enough to increase the level of serotonin alone. About one-third of patients do not respond to SSRI therapy.
Ketamine acts via the glutamate signaling pathway. Glutamate is the main neurotransmitter that makes neurons more active. Changing glutamate activity can have far-reaching effects, as it’s found in half of the connections in the brain. In high doses, ketamine separates the upper and lower levels of the brain. It cuts off man’s connection with the outside world. The person does not perceive sensations such as vision, hearing, pain and does not create memories. This feature is beneficial for patients who will receive anesthesia for surgery. Moreover, unlike many sedatives, it does not affect heart and lung functions. Therefore, it was approved for use in the USA in the 1970s.
The effect of low-dose ketamine on symptoms of depression was first noticed in the late 1990s. The antidepressant effect begins within hours of taking the drug and may continue for weeks. The pattern of action is quite different from SSRIs. SSRIs may take months to take effect, and their effect quickly wears off when they are stopped.
Ketamine appears to do more than temporarily affect glutamate signaling. It may be stimulating the release of chemicals that encourage neurons to form new connections. When combined with other treatments, such as cognitive behavioral therapy, ketamine therapy can help patients quickly form new neural connections and control their emotions. According to studies, even when SSRIs do not work, ketamine may be beneficial in more than half of patients. However, as it is a new treatment, the precaution should not be neglected. ketamine hallucinationThere is also the risk of addiction and drug abuse. Therefore, the FDA has approved its use in patients with moderate or severe depression who are unresponsive to at least two different drugs. As a result, ketamine has provided a new option in the treatment of depression via the glutamate pathway. Observing its effects may help to better understand the cellular mechanisms of depression.