If you’re seeking information on the FDA approval of ketamine for depression, you’ve come to the right place. In 2019, the FDA approved esketamine, a novel form of ketamine, specifically for adults struggling with treatment-resistant depression. This guide outlines how this approval changes the landscape of depression treatments, examines the role of esketamine in treating depression, and provides key insights into its usage and safety protocols.

Key Takeaways

  • The FDA approved esketamine, a form of ketamine, for treatment-resistant depression, offering a new option for patients unresponsive to traditional antidepressants.
  • Plus by APN integrates ketamine-assisted healing into our mental health care services with custom-dosed treatments and a luxurious clinical environment to enhance patient comfort.
  • While ketamine therapy holds promise for various mental health disorders, including depression and PTSD, the medication must be administered under professional supervision due to the potential risks of abuse, addiction, and adverse reactions.

The FDA’s Green Light for Ketamine in Mental Health

A significant milestone was reached in the treatment of mental health on March 5th, 2019, when the Food and Drug Administration (FDA) officially approved esketamine for individuals with treatment-resistant depression.¹ This decision outlines strict criteria and requires a patient to try two or more FDA-approved antidepressants without relief from symptoms – despite adequate dosage, duration, and adherence – before qualifying for ketamine treatment.

Esketamine’s approval from the FDA came after successful clinical trials and ultimately led to greater availability of Spravato, a new nasal spray ketamine medication used alongside oral antidepressants for managing adult depression cases resistant to other treatments. For those struggling with this form of depression, Spravato brought newfound hope as an innovative solution.

The uniqueness of esketamine lies in its potent mechanism, which sets it apart from traditional antidepressant drugs.² With a rapid onset action, esketamine shows improvement in depression symptoms within hours – unlike traditional depression medications that can take weeks to show improvements. Esketamine offers potential advantages in treating patients suffering from extreme depressive symptoms caused by NMDA receptor modulation issues; esketamine requires lower dosage amounts, which can result in potentially fewer adverse effects compared to regular ketamine use and other existing depression medications.

The Therapeutic Approach at Plus by APN

Plus by APN has integrated ketamine-assisted healing into our comprehensive continuum of care to treat a range of mental health disorders. Based on established research demonstrating ketamine’s efficacy in reducing depression symptoms and maintaining antidepressant effects, Plus by APN typically recommends 4-8 sessions of customized dosed ketamine treatments.

Custom dosing is a fundamental aspect of the approach taken at Plus by APN; we take our responsibility in administering ketamine therapy very seriously. We work with each patient to develop tailored ketamine treatment that caters to each individual’s specific needs and response to the medication to maximize ketamine’s therapeutic benefits. Ketamine treatment programs primarily target patients diagnosed with major depressive disorder or bipolar depression – only those who can therapeutically benefit from ketamine are eligible to receive this specialized form of treatment. 

A Look Inside Plus by APN Clinics

At Plus by APN, we treat patients with the utmost care and respect. Our ketamine treatment sessions focus on providing a comfortable experience for each patient while they are receiving in-person medical care. We organize treatments into four stages to help guide and support patients through challenging emotions or potential side effects like respiratory depression.

We thoughtfull designed our ketamine treatments clinics to provide a luxurious clinical experience for patients. Our goal is to promote relaxation while retaining full presence during psychiatric disorder treatment under the supervision of expert medical professionals. Patients have access to advanced mental health services, such as interventional psychiatry, as well as FDA-approved options like ketamine treatment. We offer residential treatment at  All Points North Lodge and innovative care services in multiple Plus by APN locations, including Malibu.

Ketamine’s Mechanism of Action Against Depression

At low doses, ketamine increases glutamate transmission in the brain to stimulate production for better cognitive function.³ This mechanism of action may help resolve a disinhibition effect on GABAergic interneurons caused by blocked NMDA receptors and trigger a heightened glutamate release. As a result, some patients may experience elevated blood pressure during treatment.

Glutamate plays an essential role as an excitatory neurotransmitter and is responsible for learning and memory processes within the brain. Its functions include transmitting signals between neurons, supporting neuronal development and survival, and promoting neurotrophic factor production to grow new connections – crucial components of optimal cognitive function.

By positively impacting neural systems involved with cognition, depression, and sensory processing mechanisms and enhancing neuroplasticity capabilities within the brain, ketamine facilitates recovery from psychiatric disorders. Patients must be closely monitored throughout treatment, as serious adverse outcomes are possible.

The mechanism behind ketamine’s efficacy against depression appears to be linked through synaptic modifications at N-methyl-D-aspartate (NMDA) receptors.⁴ This influence aims to create positive behavioral changes in individuals with psychiatric conditions.

Risks and Considerations in Ketamine Treatment

Although ketamine treatment has shown promising outcomes, it does carry potential risks. Individuals who have a history of hypersensitivity to the drug or are pregnant/breastfeeding should not receive FDA-approved ketamine formulations for treatment purposes. Those with active substance abuse problems and/or a personal/family history of schizophrenia, manic bipolar disorder, or hypomania also cannot be treated with this medication.

One notable risk associated with ketamine is its potential for misuse and addiction when used recreationally or in non-medical settings. To prevent such incidents, Plus by APN closely follows strict safety protocols and guidelines during the administration of the drug to ensure proper use and reduce adverse effects.

To mitigate any possible dangers associated with ketamine treatment at our clinics, we adhere to specific measures that facilitate prompt handling of adverse reactions. Patients can feel confident knowing they are being well taken care of throughout treatmentwith safeguard to help minimize potential risks.

At Plus by APN, we take significant precautionary steps toward ensuring patient safety through strictly regulated procedures governing all stages of the delivery of FDA-approved ketamine treatments. In doing so, we help make sure there are minimal opportunities for outflow-related events. Throughout every step of the process, we focus on quickly managing any risks, ensuring safety at each stage. Our goal is to provide the most supportive and effective care in a thoughtfully dynamic environment.

The Future of Ketamine Therapy

Ketamine, as an alternative therapeutic treatment, has the potential to effectively address a variety of mental health disorders such as depression, suicidal ideation, substance use disorder (SUD), and post-traumatic stress disorder (PTSD).⁵ Ketamine was first used as a psychiatrist medication back in the 1970s, and studies show that it can produce rapid improvement in depressive symptoms.⁶

Recent advancements in ketamine therapy for mental health conditions include FDA approval for esketamine, specifically for treatment-resistant depression. Ketamine infusion therapy has also been found effective in treating not only depression but other mental health issues as well. These developments establish ketamine’s promise as a viable option for various mental health disorders.

We are witnessing an increase in the clinical use of ketamine as researchers conduct more studies on using ketamine therapeutically.


The approval of esketamine by the FDA and Plus by APN’s innovative therapeutic approach have brought about a hopeful future for treating treatment-resistant depression and other psychiatric disorders. Although there are potential risks, strict safety protocols ensure ketamine treatment is safe and effective.

As we look ahead, ongoing research on ketamine therapy continues to reveal its potential benefits. With wider access to this treatment option in sight, we may see significant changes in how mental health conditions are managed. 

Frequently Asked Questions

When did the FDA approve esketamine for the treatment of treatment-resistant depression?

On March 5th, 2019, the FDA approved esketamine to be used in the treatment of depression that has not responded to other forms of treatment. This drug is specifically targeted towards patients with treatment-resistant depression, and it has been found to be effective.⁸

What is the therapeutic approach of Plus by APN in administering ketamine treatments?

Plus by APN’s standard recommendation for treatment involves a series of 4-8 sessions utilizing ketamine as part of our holistic health care approach. We focus on delivering comprehensive therapeutic treatment for individuals seeking relief through this particular course of action.

What is the mechanism of action of ketamine in treating depression?

Ketamine’s mode of action for depression treatment includes increasing glutamate production in the brain, leading to the development of fresh neural connections, which can promote more constructive thoughts and actions.⁷

What are the potential risks associated with ketamine treatment?

It is essential to note the potential hazards associated with using ketamine as a form of treatment. These risks include possible hypersensitivity to the drug, as well as incompatibility with specific conditions like pregnancy or current substance misuse.

Before undergoing any form of ketamine therapy, it is crucial to be fully aware of these potential dangers that may arise. Careful consideration must be given due diligence when considering this course of treatment so that all parties are satisfied.

What does the future hold for ketamine therapy?

The potential for ketamine therapy to become a prevalent and readily available treatment choice for individuals with mental health conditions that do not respond well to traditional treatments is on the horizon. Promising advancements in ketamine research help spur the shifts toward more personalized depression treatments, signaling exciting possibilities for patients seeking effective care options through the use of ketamine.

  1. “FDA Approves New Nasal Spray Medication for Treatment-Resistant Depression; Available Only at a Certified Doctor’s Office or Clinic.” U.S. Food & Drug Administration, 5 Mar. 2019, https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified. Accessed 22 Feb. 2024. 
  2. Bahr, Rebecca, et al. “Intranasal Esketamine (SpravatoTM) for Use in Treatment-Resistant Depression In Conjunction With an Oral Antidepressant.” Pharmacy and Therapeutics, vol. 44, no. 6, 2019, p. 340, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534172/. Accessed 22 Feb. 2024.
  3. Abdallah, Chadi G., et al. “The Effects of Ketamine on Prefrontal Glutamate Neurotransmission in Healthy and Depressed Subjects.” Neuropsychopharmacology, vol. 43, no. 10, 2018, pp. 2154-2160, https://doi.org/10.1038/s41386-018-0136-3. Accessed 22 Feb. 2024.
  4. Zanos, Panos, and Todd D. Gould. “Mechanisms of Ketamine Action As an Antidepressant.” Molecular Psychiatry, vol. 23, no. 4, 2018, p. 801, https://doi.org/10.1038/mp.2017.255. Accessed 22 Feb. 2024.
  5. Ramos, Carolina S., et al. “The Therapeutic Effects of Ketamine in Mental Health Disorders: A Narrative Review.” Cureus, vol. 14, no. 3, 2022, https://doi.org/10.7759/cureus.23647. Accessed 22 Feb. 2024.
  6. Shin, Cheolmin, and Ku Kim. “Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives.” Psychiatry Investigation, vol. 17, no. 3, 2020, pp. 181-192, https://doi.org/10.30773/pi.2019.0236. Accessed 22 Feb. 2024.

Abdallah, Chadi G., et al. “Ketamine’S Mechanism of Action: A Path to Rapid-Acting Antidepressants.” Depression and Anxiety, vol. 33, no. 8, 2016, p. 689, https://doi.org/10.1002/da.22501. Accessed 22 Feb. 2024.