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Andrew's Breakthrough in Treating Depression That Didn't Respond to Medication
At just 20 years old, Chloe found herself struggling with depression—a challenge that made everyday life feel overwhelming and joy hard to find. Working as a Behavioral Health Technician at Greenbrook Mental Wellness Centers, she had witnessed firsthand how NeuroStar® TMS therapy helped patients improve. It was that experience that ultimately led her to seek treatment for herself. Chloe's decision marked a turning point. She responded remarkably well to NeuroStar® TMS, echoing the very outcomes she used to celebrate in others. What followed was a transformation not only in her mental health but in her overall experience of young adulthood. The Care Team at Greenbrook played an essential role in her recovery. Chloe described the Care Team as “absolutely amazing,” noting their kindness and commitment to checking in regularly. Their support made the treatment process feel less clinical and more personal—a space of trust and comfort she looked forward to each day. As treatment progressed, the changes in Chloe’s life began to blossom. She found herself embracing experiences she once would’ve dismissed. One particular moment that stands out is a pottery class she took with a friend—except this wasn’t just any pottery class. It included cuddling baby goats and lambs while painting.
By: Mitchell Whigham, PA-C Physician Assistant, Greenbrook Mental Wellness Centers
By: Mitchell Whigham, PA-C Physician Assistant, Greenbrook Mental Wellness Centers
A recent study compared the effects of TMS therapy and Antidepressants. TMS therapy provided more relief from patients depressive symptoms compared to Antidepressants.
Learn how long it takes for different depression treatments to work such as antidepressants, TMS therapy and SPRAVATO®.
So many of us are used to those familiar names we associate with antidepressants: Zoloft®, Prozac®, Celexa, Paxil. The x’s and z’s roll off our tongues with little effort. These selective serotonin reuptake inhibitors (SSRIs) have been the most popular and commonly prescribed antidepressants since the late 1980s. Along with non-SSRIs like Wellbutrin and Cymbalta, these mostly oral antidepressants have served as the scaffolding for the nation’s mental health treatment for so long that the idea of taking psychedelics for depression and anxiety may feel absurd. But is it? In 2019, the Food and Drug Administration (FDA) approved nasal esketamine spray SPRAVATO® for treatment-resistant depression and then for major depressive disorder with acute suicidal ideation or behavior in 2020. Derived from ketamine , a dissociative anesthetic drug with hallucinogenic properties, this treatment is the closest the United States has come to implementing psychedelics for depression. Still, ketamine is more of a psychedelic-like medication, not a psychedelic in the same sense as psilocybin or LSD (lysergic acid diethylamide). Could those psychedelics eventually become the leading antidepressants? The Scientific Difference Between Psychedelics and Antidepressants Standard antidepressants, such as SSRIs, tricyclic and tetracyclic antidepressants, and monoamine oxidase inhibitors (MAOIs), all work to elevate the levels of monoamine neurotransmitters in the brain. Serotonin, dopamine, norepinephrine, and epinephrine (adrenaline) are all monoamines. They help regulate mood, emotion, the fight-or-flight response to fear, attention, memory, sleep, and function. According to the monoamine hypothesis, depression is a result of low monoamine levels in the central nervous system. Because standard antidepressants increase monoamines, they can help treat depression symptoms. Unfortunately, antidepressants can take weeks to kick in, and around one-third of people taking antidepressants will continue to experience symptoms during standard antidepressant treatment. Put simply, depression is a complex condition, and the monoamine hypothesis can’t explain every case. This is where psychoactive antidepressants come in. Ketamine and psychedelics for depression and anxiety have been shown to act more quickly to relieve symptoms of depression. Importantly, while ketamine is a dissociative drug, it is not a classic psychedelic like LSD or psilocybin. How do Psychedelics Work for Depression? In addition to elevating monoamine levels, ketamine and psychedelics for depression work by acting on amino acid neurotransmitters. They increase neuroplasticity by impacting the most prolific excitatory neurotransmitter, glutamate, which helps us perform cognitive functions pertaining to memory, learning, and thinking. Ketamine and psychoactive antidepressants also act on gamma-aminobutyric acid (GABA), an amino acid neurotransmitter that regulates brain activity and helps prevent issues with anxiety, depression, sleep, irritability, and concentration. Perhaps because of the way they impact the brain differently than standard antidepressants, psychedelics have been shown to have a more lasting effect. A study in the February 2022 issue of the Journal of Psychopharmacology reported that after two carefully controlled doses of psilocybin spaced two weeks apart, 75% of participants reported improved symptoms. Even more encouragingly, 58% of participants were still in remission from depression at the 12-month mark. Psilocybin has yet to gain FDA approval for treating depression, but this study highlights the important relationship between psychedelics and depression treatment. Unlike standard antidepressants, which must be taken every day and can come with side effects, psilocybin appears to relieve symptoms after one or two doses. With psilocybin and other psychedelics, as well as ketamine, side effects tend to last only during the treatment session and end shortly thereafter. A caveat is that due to the minuscule but worrisome risk of developing psychosis after taking dissociative or psychoactive medications, psychedelics and ketamine may not be appropriate for people with a family history of psychosis. How Ketamine is Similar to Psychedelics Like psychedelics, ketamine can cause dissociation and hallucinations, and the two types of medications work similarly to improve symptoms of depression. However, psilocybin, LSD, and other psychoactive antidepressants do this by completely overriding the brain’s inhibitory framework. Ketamine, on the other hand, relaxes it. The overriding is why classic psychedelics produce a much stronger and less relaxing “trip.” In studies on psychedelics and depression, patients go through much longer treatment sessions with psilocybin than with ketamine. The observation period after psilocybin treatment is six hours, for example, compared to the two-hour waiting period after ketamine treatment. However, psilocybin’s more intense nature may give it an edge over ketamine. When a patient undergoes FDA-approved nasal esketamine spray treatment, they start out with two treatment sessions a week for four weeks, followed by once-weekly sessions for another four weeks. After this, they may come in for nasal esketamine treatment once every week or two to maintain remission from depression. Psilocybin can be effective after far fewer doses, and its positive effects may last longer than nasal esketamine spray. The difficulty, of course, is that psilocybin and LSD are Schedule I controlled substances, meaning that they have a high potential for abuse, and the FDA currently does not recognize any medical benefits they may have. Ketamine, on the other hand, is a Schedule III controlled substance, which means it holds the potential for abuse but has recognized medical benefits. Psilocybin is also beginning to gain traction as a legitimate psychoactive antidepressant. The state of Oregon decriminalized psilocybin and approved its therapeutic use in 2020. Cities such as Denver, Colorado; Oakland and Santa Cruz, California; Washington, D.C.; and Somerville, Massachusetts have also decriminalized psilocybin. Psychedelics and Depression: A Promising Future Because they are fast-acting and long-lasting, psychedelics for depression may be a game-changer for mental health. However, FDA approval may not come until 2025 or later, and even then, the stigma of psychedelics may pose a roadblock to widespread psychoactive antidepressant treatment. While the future is promising, we are still in the experimental phase for psychedelics and depression. Even now, we lean on standard antidepressants as we explore new options. For example, nasal esketamine spray (SPRAVATO®) must be taken alongside an oral antidepressant. The good news is that nasal esketamine spray, which works similarly to psychedelics, is FDA approved, covered by insurance, and available at Greenbrook. We offer nasal esketamine spray consultations , along with transcranial magnetic stimulation (TMS) treatment for those who would rather not try nasal esketamine spray. Learn how TMS works here. To get started with nasal esketamine, schedule a free consultation with Greenbrook. We look forward to helping you find relief from 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.
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