As a physician, I’ve seen many patients diagnosed with clinical depression. This was especially true during my time as an ER doctor. Traditional methods treat depression with conventional pharmaceuticals, specifically antidepressants such as SSRIs.
Today, one in ten Americans over age 12 are prescribed antidepressant medications. While the numbers seem to be increasing, most patients aren’t getting the relief they hoped for.
Recently, the medical industry has been looking at ketamine as an emerging solution for depression. Initially used as an anesthetic drug, there is growing evidence that ketamine may help with treatment-resistant depression. It may also alleviate other mental health symptoms.
Like an old dog with new tricks, research is continually finding new ways to use older therapeutics and medications. Another example of this is the tricyclic antidepressant, Amitriptyline. Once used for depression, it is now used to help with chronic pain conditions such as Interstitial Cystitis.1
As a physician, I take a comprehensive mind-body approach to understanding my patient’s symptoms. It is well known that mental health is an underlying contributor to many chronic illnesses and diseases. My goal is to address lifestyle habits and review all possible courses for treatment and healing.
In this article, I’m discussing the benefits of ketamine as a treatment for depression. I’ll discuss the symptoms and weigh the potential risk factors associated. First, let’s learn more about how ketamine came to be.
What is Ketamine?
Ketamine was first developed in the 1960s and became FDA-approved in the 1970s as a general anesthetic drug. It is widely administered to children, adults, and pets to help calm and sedate them before surgical procedures.
This drug is a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor for glutamate. It produces an altered state where patients may appear to be awake, but have drastically reduced sensory responses.2
Today, ketamine still plays an essential role in anesthesiology. It keeps heart rates stable while effectively sedating the patient. In fact, I used ketamine quite frequently in the pediatric ER during suture lacerations on the face or other difficult locations.
Ketamine is considered what we refer to as a ‘quick on and off drug’. Since the drug is administered by IV, it works quickly and has a short half-life. It’s wonderful for minor and relatively minor procedures. It’s also well tolerated and safe for use in children.3
Over the last decade, more and more studies looked at treating depression with ketamine. In 2019, the FDA approved ketamine as a prescription medication for clinical depression. Studies show that ketamine induces changes in the brain responsible for maintaining depression remission.4
Ketamine has been approved for people with treatment-resistant depression. This is groundbreaking for those who’ve tried at least two other antidepressants (SSRIs) and haven’t experienced remission.
It’s important to note that while ketamine is not classified as an opioid, it has been shown to produce minor hallucinogenic effects. In some cases, it can also produce a brief altered psychotic state. Ketamine is classified as a “dissociative anesthetic.” Instead of acting on the 5-HT system, it acts on the glutamatergic system. Although it does not produce a psychedelic “trip,” it is still considered a hallucinogen.5
How Ketamine Works
Promising research enabled the FDA to expedite the approval process. This enabled the drug to be more quickly and readily available to the public. Since 2019, ketamine has been used as a treatment for depression, prescribed in microdoses of 0.1 to 0.5 mg/kg.
Researchers have identified ketamine-induced changes in brain activity that can help keep depressive behaviors in remission.6 It’s also found to be a fast-acting antidepressant, relieving depressive symptoms within just hours. This makes this a solid medicine for those experiencing treatment-resistant depression.
A clinical study was conducted to understand the role ketamine plays in serotonergic pathways. The study concluded that ketamine benefits the increase of prefrontal serotonin release, rapidly eliciting antidepressive effects.7
A report published in 2018 found that ketamine binds to NMDA. This creates anesthetic and analgesic properties.8 This increases the amount of glutamate, a neurotransmitter, which activates the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) receptor. This then leads to synaptogenesis, the formation of synapses between neurons in the nervous system. This process likely affects mood, thought process, and cognitive function.9
Most general anesthetic drugs interact with many receptors in the central nervous system (CNS). When they interact with γ-aminobutyric acid (GABA) receptors, they can induce hypnosis, depression of spinal reflexes, and amnesia. Unlike other anesthesia, ketamine does not interact with GABA receptors. This makes it a much safer option.10
What are Ketamine’s Benefits?
Promising research has been conducted to conclude ketamine provides therapeutic benefits and relief within just hours to patients with depression. Studies also suggest ketamine may have a positive effect on other mental health conditions, such as anxiety, schizophrenia, and post-traumatic stress disorder (PTSD)
With mental health disorders on the rise, this is the perfect time to explore alternate treatment modalities and therapies.
An Alternative to Opioids
16% of Americans who have mental health disorders receive over half of all opioids prescribed in the United States.11 By exploring alternative options, healthcare providers can help reduce the number of prescriptions.
A study found that ketamine exhibits anti-inflammatory effects by suppressing the inflammatory response.12 This makes it a possible treatment for pain management. Ketamine’s antidepressant effects, combined with reducing opioid tolerance, make it a preferred drug for managing pain.
Success in Treating Mental Health Disorders
The only pharmacological treatments approved for PTSD by the FDA are SSRIs. However, SSRIs are used as a maintenance therapy, not as a means of remission.13 One study evaluated the efficacy of ketamine use in the treatment of chronic PTSD over two weeks. Patients showed reduced symptoms of avoidance, negative mood swings, and intrusive thoughts within 24 hours post-treatment.14
The use of ketamine has also been studied as a treatment option for those with suicidal thoughts. One analysis showed that ketamine given IV or intranasally reduced the number of suicidal thoughts within 24 hours.
Schizophrenia is a disorder characterized by symptoms such as hallucinations, delusions, and dissociative behavior. The neurotransmitter glutamate and NMDA receptors are central to brain functions. As previously discussed, ketamine increases glutamate levels. A study conducted indicates a strong link between glutamatergic neurotransmission and glutamate levels. This makes ketamine a potential treatment for schizophrenia.15
Does Ketamine Work for Depression?
Ketamine, known for its anesthetic properties, has been found to exert antidepressant effects. Recent clinical trials have reported that ketamine’s benefits include rapid antidepressant effects in patients suffering from treatment-resistant depression. A study by the National Institute of Mental Health (NIMH) reviewed the effects of ketamine on mice. Researchers found changes in behavioral and neural activity taking place within just three hours after ketamine treatment.16
Further reports have indicated that low doses of ketamine can be administered for potential therapeutic management of depression.17 Research suggests that microdosing ketamine for depression can provide therapeutic benefits within hours. This is a drastic improvement as opposed to traditional antidepressants (SSRIs). For anesthesia purposes, 6.5 to 13 mg/kg of ketamine is administered for sedation.18 Whereas 0.1 to 0.5 mg/kg of ketamine is prescribed for depression treatment.
Ketamine works by increasing glutamate, which affects memory and learning. In some trials, ketamine rapidly reduced depression symptoms and provided relief for several days. Again, this is a much faster response than traditional treatment methods such as SSRIs. These trials show ketamine’s benefits potentially relieving feelings of sadness, helplessness, and even thoughts of suicide.19
As previously discussed, ketamine is an NMDA antagonist drug that increases the amount of glutamate, a neurotransmitter, which activates the AMPA receptor. This leads to synaptogenesis, the formation of synapses between neurons in the nervous system. Within 24 hours of the first dose, synaptic connections begin to provide better antidepressant effects for those resistant to other depression treatments.20
What are the Risks?
With any pharmaceutical, you run the risk of possible side effects. These can include increased dependence and long-term health complications. When deciding to take a prescription, it comes down to consulting with your doctor. Together, you and your healthcare provider can evaluate whether the benefits outweigh the risks, and if it is the right prescription for your body.
With the recommended dose administered intravenously between 0.1mg/kg and 0.5 mg/kg, you may experience common side effects such as:
- Double vision
- Feelings of unease
When overconsumed in high doses, adverse health effects may become present, causing the following:
- Heart arrhythmias
- Liver injury
- Psychiatric episodes (hallucinations, panic attacks, dysphoria, etc.)
- Muscle spasms
- Respiratory depression
It is important to mention a long list of drug interactions associated with ketamine. Make sure to discuss all medications you are currently taking with your physician to avoid adverse reactions.
A Word of Caution: Drug Abuse & Sexual Assault
In 2016, a study cautioned against ketamine abuse due to its hallucinogenic properties. Ketamine is pharmacologically similar to phencyclidine (PCP), a hallucinogen, anesthetic, and painkiller. Due to its natural ease for tolerance build-up, ketamine abuse has become a common worldwide health concern. According to the National Institute on Drug Abuse (NIDA), ketamine can cause serious delayed health effects,21 such as the following:
- Bladder pain and ulcers
- Kidney issues
- Chronic stomach pain
- Longer-term memory deficits
It is important to note that ketamine is potentially fatal in alcohol-intoxicated patients. It is therefore advised to avoid drinking while taking this prescription drug. Ketamine is also labeled a “date rape” drug due to its sedative properties. Due to the nature of this substance, it is often used by predators leading to sexual assault.22
How is Ketamine Administered?
Ketamine is administered in a medical facility by a nurse or trained health professional.23 This medicine is either given as a shot into your muscle or intravenously, taking about 45 to 60 minutes to administer. When administered through IV, people usually respond well within one to three infusions. Please note that a physician or a licensed clinic should always administer ketamine.
Ketamine can also be prescribed intranasally as a nasal spray called esketamine. Esketamine is derived from part of the ketamine molecule.
Similar to ketamine, your perception can become altered during the first hour or two after treatment. In-clinic visits are necessary for intranasal administration. During your visit, three doses are given spaced five minutes apart. The doctor will then observe for any potential side effects before releasing you to go home.
The benefit of ketamine is that it is absorbed rapidly. Ketamine has a bioavailability rate of around 93%. After the drug passes through the metabolism, only 17% of the administered dose is absorbed.24 It distributes very quickly and presents a distribution half-life of 1.95 minutes.
The downside to ketamine is the associated cost. While it is readily available and offered at many health clinics, the price can be steep. The price ranges from $300 to $1,200 per dosage, making it a potentially less affordable option compared to SSRIs.
Support Brain Health with NeuroLive™
The traditional route of taking pharmaceuticals may not be right for you. This is especially true if you are experiencing other chronic health symptoms. There are alternative solutions to supporting optimal mental health.
Our brains are tied to our gastrointestinal tract, after all, the gut is known as our second brain. About 90-95% of our serotonin is made in our gut. One key to treating mood imbalances is to recognize that most are actually rooted in your gut, not your brain.
I see many patients with mental health disorders who are interested in pursuing an alternative medicine route for support. For those patients, I recommend my Neurolive™ formula. This provides brain-nourishing nutrients and supports your cognitive function. It addresses the multiple pathways involved in neurological health by supporting oxidant and cytokine balance, methylation, mitochondrial function, and endocrine balance.
My Neurolive™ supplement is formulated with seven targeted micronutrients to help maintain healthy memory, focus, and cognitive function. It contains Sharp•PS® GREEN, the highest-quality brain cell membrane support on the market today.
Neurolive™ also contains two vital amino acids, L-Theanine and N-acetyl cysteine (NAC). L-Theanine supports a calm and relaxed state of mind, whereas NAC replenishes glutathione and regulates glutamate levels. Together, these ingredients boost brain health.
In addition, Neurolive™ is formulated with vitamin B6 in its coenzyme form to support optimal neurotransmitter balance and cognitive function support. I also included herbals such as Bacopa, Mucuna Pruriens, and Ginkgo to support healthy vasculature and optimal blood flow.
The Final Word on Ketamine’s Benefits
Ketamine is an analgesic drug that offers more than simple sedation. When given in small amounts, it can be a safe and effective treatment for depression. Aside from the proven efficacy of ketamine for treatment-resistant depression, there are alternative therapies you can try.
One such therapy is my Neurolive™ formula. Talk with your doctor if you are experiencing symptoms of depression or other mental health-related conditions.
- Antidepressants for IC/BPS Symptoms. Interstitial Cystitis Association. .
- Ketamine: 50 Years of Modulating the Mind. Linda Li and Phillip E. Vlisides. Frontiers in Human Neuroscience. 2016.
- What is the evidence for the safety and efficacy of using ketamine in children. G Dolansky, BA (Hon), et al.. Pediatrics Childrens Health. 2008.
- Ketamine Reverses Neural Changes Underlying Depression-Related Behaviors in Mice. . National Isntitue of Mental Health. 2019.
- Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine. Danilo De Gregorio, et al.. The Journal of Neuroscience. 2021.
- Ketamine as a therapeutic agent in major depressive disorder and posttraumatic stress disorder: Potential medicinal and deleterious effects. Bhuvi Sachdeva, et al.. Wiley Online. 2023.
- Ketamine-Induced Prefrontal Serotonin Release Is Mediated by Cholinergic Neurons in the Pedunculopontine Tegmental Nucleus. Haruko Kinoshita, et al.. Int J Neuropsychopharmacol.. 2018.
- Ketamine: NMDA Receptors and Beyond. Danilo De Gregorio, et al.. J Neuroscience. 2016.
- Ketamine for major depression: New tool, new questions. Bhuvi Sachdeva, et al.. Harvard Health. 2019.
- Intravenous Ketamine Use for Patients With Chronic Pain Conditions. Millicker, Megan. Pain Management. 2020.
- Prescription Opioid Use among Adults with Mental Health Disorders in the United State. Matthew A Davis. J Am Board Fam Med. 2017.
- Ketamine for pain management. Bell, Rae Frances. J Am Board Fam Med. 2018.
- The Therapeutic Effects of Ketamine in Mental Health Disorders: A Narrative Review. Carolina Sepulveda Ramos, et al.. Cureus. 2022.
- The use of ketamine to cope with depression and post-traumatic stress disorder: A qualitative analysis of the discourses posted on a popular online forum. Tharcila V Chaves, et al.. Am J Drug Alcohol Abuse. 2020.
- Glutamatergic dysfunction in Schizophrenia. Andreas O. Kruse. Translational Psychiatry. 2022.
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. Gerard Sanacora, MD, PhD, et al.. JAMA Psychiatry. 2017.
- Ketamine: a new look to an old drug. G. Ivani, et al.. Minerva Anestesiol. 2003.
- Ketamine Dosage. Drugs.com. 2023.
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers. Dmitriy Matveychuk, et al.. Alcohol and Drug Foundation. 2020.
- Ketamine for Depression: What to Know. Sonya Collins. WebMD. 2022.
- Ketamine Abuse: Addiction, Effects, and Treatment. Lauren Geoffrion, M.D.. American Addiction Centers. 2022.
- Drug Facilitated Sexual Assault. U.S Department of Justice. .
- Ketamine (Injection Route). Mayo Clinic. 2023.
- Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J A Clements, W S Nimmo. J Pharm Sci. 1982.