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How Does Ketamine Work for Depression?

 

2022-07-29T21:58:40Z

Medically reviewed on by

Dr. Steven Harvey

Regional Medical Director Greater St. Louis

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.

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Starting any medical treatment for the first time can leave you with questions, especially if you’re looking forward to the benefits it may bring. It’s no different when you’re preparing for your nasal esketamine treatment. Your previous mental health treatments may have consisted solely of taking antidepressants at home or visiting a therapist’s office for cognitive behavioral therapy (CBT), so nasal esketamine is probably a new treatment experience for you. If you're wondering what it's like to start nasal esketamine and get ready for your first session, keep reading. Getting Started with the Nasal Esketamine Treatment As with any new treatment, you’ll first talk to your primary care provider or psychiatrist about whether nasal esketamine is a good fit for you. Alternatively, you can schedule your esketamine nasal spray consultation with a treatment center (such as Greenbrook) that has certification by the FDA’s Risk Evaluation and Mitigation Strategy (REMS). At Greenbrook's REMS-certified nasal esketamine treatment centers, our Greenbrook-affiliated psychiatrists and psychiatric nurse practitioners will review your medical history and also conduct our own assessment to help determine whether nasal esketamine treatment is right for you. Certain conditions, including blood vessel disease and a history of psychosis, may make treatment a risk for you. Make sure you discuss all previous and present conditions with your doctor or nasal esketamine provider before beginning treatment. If the medication is deemed a good fit, you’ll receive your prescription from the Greenbrook-affiliated provider. Your Greenbrook Care Team will put together a personalized care plan for the weeks and months to follow. Keep in mind that you will need to take a standard (oral) antidepressant along with your nasal esketamine treatment. There are two important regulations to note when it comes to preparing for treatment: Each treatment is followed by a mandatory two-hour observation period. This means you will need to plan to stay at the center for at least two hours following your self-administration of the esketamine nasal spray. You cannot drive during the rest of the day after treatment and must arrange for transportation. These regulations are mandatory. It may be helpful to sit down and plan out several weeks’ worth of transportation once you know your treatment schedule. In addition, if you’re wondering what to bring for the treatment, we recommend entertainment such as an audiobook or playlist of favorite songs and a pair of headphones. You may want them during the two-hour observation period. What to Expect During Nasal Esketamine Treatment On the day of treatment, you’ll need to stop eating any food two hours before your appointment and stop drinking all fluids 30 minutes before you come in. 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Should you be left with a metallic taste by the spray, the Care Team will offer suckers to help make the flavor dissipate. After your dose, you’ll be encouraged to lie back in your comfortable recliner. While most patients enjoy a quiet setting, Greenbrook is prepared to accommodate patients with a more animated reaction to the medication. You may feel sleepy, dizzy, mildly dissociated, and/or nauseated during treatment. Greenbrook's Care Team is readily available if you need assistance. How to Prepare for after your Nasal Esketamine Treatment  Most side effects begin to wane in the second hour of observation, but if you’re wondering, “Is it safe to drive immediately after nasal esketamine treatment?” the answer is a resounding no. In addition to the mandatory ride home, you will need to block off time to rest and let side effects fully dissipate. This extended rest period is especially important in the first weeks of treatment when you’ll have treatment twice a week. Do not drive or operate machinery of any kind until the day after treatment. Just take it easy, relax, and take care of yourself. If you’re unsure what activities you can do or should avoid during this time, talk to your Care Team for more information. While side effects tend to dissipate completely after a good night’s sleep, many nasal esketamine patients begin feeling relief from depression symptoms within hours of their treatment. Other Tips in Preparing for Your Nasal Esketamine Treatment At Greenbrook, we make every effort to schedule your treatment in the afternoons or whenever it is most convenient for you. We encourage you to see each treatment session as an opportunity to relax and take care of your mental health. If you have any questions or concerns, talk to your doctor or the Greenbrook Care Team. At Greenbrook, we’ll help you feel at ease when preparing for each treatment session. Schedule A Free Consultation To get started with nasal esketamine, schedule your free consultation today.
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