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Mechanisms and Advantages of Using Spravato for Depression Relief

Spravato (esketamine) is a relatively new treatment option for depression, but today has been approved by the FDA as an option for treatment-resistant depression.
Millions of people suffer from major depressive disorder today, nearly one-third of which develop treatment-resistant depression. For this, one-third of individuals who do not respond to traditional antidepressants need alternative options to help control symptoms. For those, questions like “Can spravato make depression worse?” and “How does spravato help depression?” are common.

Understanding Spravato (Esketamine)

Spravato is an FDA-approved medication, approved in 2019. Spravato for depression has been approved as a nasal spray, which is used in conjunction with an antidepressant or antipsychotic.
So what is Spravato spray for depression, exactly? Spravato is a derivative of ketamine, which is PCP or “Angel Dust.”

spravato for depression relief

Ketamine was originally used in the 1970s as an anesthetic for surgery. Since that time, the use of spravato for depression has been investigated by researchers at Yale. Since that time, it has come to light that spravato treatment-resistant depression efficacy is high and instant. The fast results associated with spravato depression treatment make it ideal for anyone experiencing suicidal ideations.

The Chemistry Behind Esketamine

Esketamine has slightly different chemical properties than ketamine and other antidepressants.
Ketamine (or RS-ketamine) is a racemic mixture with equal levels of:

  • R-ketamine and
  • S-ketamine (or esketamine)

So, other ketamine treatments, like an IV infusion, have both.

Esketamine nasal spray spravato for treatment-resistant depression is the generic name of the new medication, which does not have both, but instead only has esketamine. The chemical name is (S)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride.

The esketamine hydrochloride comes in a water soluble powder, so it is combined with other water and liquids to create the nasal spray.

Mechanism of Action

What is the main mechanism of action behind spravato and other antidepressants?

The nasal spray and similar ketamine based treatments work by growing synapses in the brain that have previously died and increasing glutamate receptors which are located on the ends of each nerve cell. This enhances the ability of your nerve cells to receive messages. Many people with depression including treatment resistant depression have deactivated or weak glutamate receptors which inhibits communication but this medication improves it.

Traditional antidepressants, or SSRIs, increase serotonin in your brain by blocking the reuptake of serotonin. This means that however much gets released, it doesn’t get reabsorbed so that your body can have higher resting levels.

How Does Spravato Help Depression?

Esketamine affects the brain’s neurotransmitter systems by activating the growth of new synapses and glutamate receptions.

By improving NMDA receptor modulation, spravato offers significant improvement in communication in the brain. It does this rapidly, encouraging fast relief from depressive symptoms compared to other treatments, which, in large part, makes it ideal for anyone experiencing suicidal ideations.
Clinical trials and outcomes demonstrate its efficacy specifically for treatment-resistant depression, with many people experiencing improvement in symptoms right away and around one-third experiencing remission.

Administration and Safety

With esketamine nasal spray spravato for treatment resistant depression, you will go to a clinic where you will be seated comfortably and a doctor will provide you with the nasal spray. That same doctor will explain how to use the nasal spray and how much to use and then monitor you as you use it in accordance with the rules.

Prior to administration you’ll have to review safety procedures and sign documentation acknowledging that you understand the risks and will remain under supervision for 2 hours after each dose in order to monitor for potential side effects.

This monitoring requirement is an FDA requirement, and all clinics offering spravato for depression must adhere to this monitoring to ensure that there aren’t serious side effects that happen immediately after. For example, doctors will test your blood pressure before and after you have used the nasal spray to look for any potential high blood pressure.

You will be required to have someone drive you after each appointment because of the high rates of drowsiness and problems with mental clarity.

In addition to the monitoring requirements in the clinical setting, you will be given a list of things to look for and when to report to a doctor if you experience specific safety and side effects.

Safety and Side Effects

There are some common and more serious side effects that are associated with spravato spray for depression.

  1. This medicine can cause mental changes like dissociation, high blood pressure, and drowsiness, which are among the more common side effects that tend to go away after a short time. For this, safety measures are taken during your treatment sessions, with your doctor checking for these effects and monitoring you, and with someone else required to give you a ride after your treatment.

  2. This medicine can cause more serious side effects like lung or breathing problems, which is why you will remain under supervision after each treatment session for 2 hours so that your doctor can check for signs of trouble breathing, irregular breathing, or indicators of respiratory depression.

  3. The spravato treatment for depression can cause side effects after you have taken it, including bladder problems, so if you notice, after your sessions, that you have difficulty urinating, painful urination, or bloody or cloudy urination, you’ll have to speak with your doctor right away. Rest assured that you’ll be given a list of all potential side effects and complications and when you should reach back out to a doctor.

  4. The most serious side effects of spravato spray for depression is that in some people, it can cause irritability, suicidal thoughts, or increased depression. Contact a doctor right away if you have sudden and strong feelings of violence, anger, or suicidal ideations.

Potential Risks and Considerations

Can Spravato make depression worse? Spravato publications indicate that on rare occasions, Spravato for depression does lead to worsening symptoms or suicidal ideations in those who may not have experienced suicidal ideations originally.

This is something to discuss with your doctor or other medical health professionals so that you can review the likelihood of such a potential risk when considering spravato treatment for depression.


How does spravato help depression? It offers several benefits through its primary mechanisms by causing actual changes in the brain rather than inhibiting the reabsorption of things like serotonin. By improving the growth of things like glutamate receptors, nerves and neurological communication get improved and brain function goes up. This improves mood and overall reception in the brain doing away with many depression symptoms.

However, if you are struggling with treatment-resistant depression, it’s important to get professional medical guidance when choosing the right depression treatments.

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