How Does Ketamine Work for Depression?

Deciding to try ketamine treatment for depression can feel promising, especially if you’ve been using antidepressants for years and are ready to explore how an alternative treatment might help you. Excited as you may be, you might also wonder, “How exactly does ketamine work for depression?” It’s perfectly understandable to want more information on how ketamine works compared with standard antidepressants. There’s a reason that the FDA approval of nasal esketamine spray is a groundbreaking step forward for mental health. So, how exactly does ketamine work in the brain?

The Science Behind How Ketamine Works for Depression 

Researchers aren’t 100% sure how ketamine works in the brain, but what they do know is fascinating. The answer partly depends on how depression has affected a person’s brain. Depression can cause you to lose synapses, the points of contact that allow nerve cells to communicate with each other. Research has shown that ketamine can help synapses begin to regrow within 24 hours after treatment. The more synapses regrow, the more relief a person feels from symptoms of depression. 

Ketamine also acts on the glutamatergic system. Glutamate is an excitatory neurotransmitter that helps nerve cells, particularly those involved in mood regulation, communicate with one another. Ketamine increases glutamate signaling, helping stimulate those weakened connections. It also acts on gamma-aminobutyric acid (GABA), a neurotransmitter thought to help regulate anxiety, fear, and stress. 

How Ketamine is Different from other Antidepressants

Unlike antidepressants, ketamine targets amino acid neurotransmitters and monoamine neurotransmitters, whereas standard antidepressants only affect monoamines. 

Amino acid neurotransmitters like GABA and glutamate account for roughly 80% of the neurotransmitters in the central nervous system. Monoamines like serotonin, epinephrine, and dopamine—which help regulate mood, pleasure, and learning—make up the other 20%.

Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and cyclic antidepressants all work to increase monoamine levels in the central nervous system. While they can be effective, they often take anywhere from two to six weeks to work. For some people, these monoamine-targeting antidepressants never work at all.

You may be wondering, “How long does ketamine take to work for depression?” Ketamine acts much more quickly than standard antidepressants, often within just hours or days of starting treatment. While it’s not a quick fix for everyone, many patients report feeling markedly better shortly after they begin ketamine IV therapy or esketamine nasal spray. Researchers believe this is partly because ketamine targets amino acid neurotransmitters and monoamines. 

If you’ve tried two or more oral antidepressants with little to no success, you may be a good fit to try ketamine for depression. Keep in mind, however, that the FDA currently requires you to take an oral antidepressant along with SPRAVATO®, the only FDA-approved, ketamine-based depression treatment

How to Speak to Your Doctor about Ketamine

If you feel as though antidepressants aren’t helping, talk to your doctor about esketamine nasal spray. While some doctors may feel reluctant to prescribe ketamine IV therapy since it is not FDA approved for treating depression, they should be willing to explore esketamine nasal spray. 

SPRAVATO® is made with a form of ketamine called esketamine. It is FDA-approved for treatment resistant depression (TRD) and major depressive disorder with suicidal ideation (MDSI). Because of this, treatment is covered by insurance.

You don’t need a referral from your primary care provider to begin SPRAVATO®. At Greenbrook, we offer nasal esketamine spray consultations to determine whether SPRAVATO® is right for you. Our Greenbrook-affiliated psychiatrists and psychiatric nurse practitioners can recommend and prescribe SPRAVATO® based on their evaluation of your mental and physical health. 

We do encourage you to keep your primary care provider and/or psychiatrist in the loop, however, as this gives you the ability to make informed decisions about treatment. Certain conditions, including pregnancy and a history of psychosis, may mean esketamine isn’t a good fit. Esketamine can also come with notable side effects, including dissociation, sedation, nausea, and a temporary spike in blood pressure. At Greenbrook, you’ll be carefully monitored during the mandatory two-hour observation period following each esketamine treatment session.

If your provider does not think esketamine nasal spray is right for you based on your medical history or past reactions to ketamine, transcranial magnetic stimulation (TMS) is an excellent, drug-free option.



Schedule a Consultation at Greenbrook

Our SPRAVATO® REMS-certified clinics are a comfortable and relaxing setting for your ketamine-based treatment for depression. We provide private rooms or bays for your treatment sessions yet can accommodate multiple patients at once, meaning you won’t experience delays in treatment. Your Greenbrook Care Team will attend to your needs from the beginning to the end of each session. 

We also provide TMS therapy should you prefer a medication-free option with fewer side effects. Schedule a free consultation with one of our Patient Consultants to learn more about how we can help lift the fog of depression.