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Intranasal esketamine for Depression | Another Stab in the Dark?

Last Updated on June 21, 2024 by Carol Gillette

Alternative to Meds Editorial Team
Medically Reviewed by Dr Samuel Lee MD

With the introduction of intranasal esketamine for depression, we see an example of drug companies repurposing older drugs, including anesthetics and psychedelics to treat stubborn symptoms like MDD. Esketamine is only approved to treat patients who did not experience relief after at least 2 courses of treatment with “traditional” antidepressants.

As reported in the 2013 BMJ, a large share of people taking antidepressants do not benefit from drug-based therapy.21 This may have opened a large market share for novel treatments that are unproven, but profitable in the short term for their manufacturers. We know there’s a better approach.

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What is Intranasal Esketamine/Spravato?

Spravato(c) is a brand name for generic esketamine, a drug in a nasal spray format, that is to be taken with an additional SSRI or SNRI drug and is prescribed to treat MDD (extreme depression) in adults. It is not approved for children, and is not recommended for elderly patients. Additionally, esketamine has a high potential risk for abuse and addiction, and long-term effects are unknown, according to recent clinical research.22,23

Ketamine is the parent drug. Ketamine’s structure looks like 2 mirror-image molecules, one of which is esketamine, and is the one used in Spravato. Injectable Ketamine is a rapid-action profound anesthetic used before surgery. In pill form, Ketamine has also become popularized as a recreational street drug. Ketamine in nasal spray form is not approved or recommended by the FDA for safety reasons. It cites concern over brain lesions in animal studies, and that it cannot regulate or approve compounded versions of drugs.1-9,11

The side effects of both esketamine and Ketamine are very similar. However, the guidelines for prescribing these 2 drugs are very different — the anesthetic Ketamine is injected only once pre-surgery, while esketamine is designed to be used intranasally, in a monitored setting, once or twice a week over a period of many months to treat MDD.

What are the Side Effects of Intranasal Esketamine?

A common side effect of intranasal esketamine for depression is mental impairment that requires the person not drive, or operate machinery for at least 24 hours after a dose it taken. Strict guidelines are in place that mandate the drug be given in a controlled lab with specially licensed caregivers in proximity to monitor and assist the person during administration and for some hours post treatment before the patient can be safely transported back home.3-8

Common side effects of intranasal esketamine can include:
  • suicidal thoughts and behaviors
  • seizures
  • death of brain cells
  • liver impairment, urinary & bladder problems
  • increased heart rate
  • hallucinations, visual disturbances
  • diminished consciousness
  • difficulty thinking clearly or remembering, confusion, disorientation
  • long-term cognitive impairment
  • elevated blood pressure
  • respiratory depression
  • nausea, vomiting
  • sudden or severe headache
  • visual disturbances
  • anxiety, feeling panic-stricken
  • irritability
  • sedation
  • disassociation
  • dizziness, vertigo
Other side effects which are less common, include
  • allergic reactions
  • difficulty breathing
  • difficulty swallowing
  • hives or rashes
  • swelling of the face, lips, tongue, throat
  • drop in blood pressure

Intranasal Esketamine and Pregnancy

Intranasal esketamine is not safe during pregnancy or breast-feeding as it may harm the baby. Avoid it during pregnancy, and at least 6 weeks before planning a pregnancy, or if you are of childbearing age and sexually active.3

Long-Term Results of Antidepressants

The most prominent type of treatment to address depression and other mental health symptoms is built on the idea of drugs that can, for some, reduce symptoms over the short term. But longer term transformation back to a healthy state is not built into the blueprint of psychiatric drug treatment.

did your prescriber consider your unique needsA human being is more than a bag of chemicals. Drug trials in the main are extremely short, and results are often inconclusive, even when they aren’t skewed by vested interests or written by authors employed by drug companies.20 Viewing mental health in this short-sighted way is a formula for failure, as the statistics clearly show. Limited efficacy of drug-based treatment, coupled with the likelihood of withdrawal phenomena when the drug is stopped are sound reasons to consider treatments that do aim for transformative results, without inflicting harm to the patient.12-16

A glaring example of how generally limited drug trials are, out of thousands of drug trials one can study, not a single one has a word to say about what the participants’ diets were like, or whether nutritional deficits were present, checked for chronic sleep problems, toxic exposures, or other issues prior to treatment. These and many other factors are ALL of prime importance in getting a true picture of an individual’s health.19

A Note on Suicidality in Treating Depression

As a note, suicidality is associated with those suffering extreme psychological pain. Rather than a “wish to die,” the condition is often viewed as a means of escape from this unrelenting torment. Clinical trials have observed that something as mild as a supportive approach to the person, asking where the unbearable emotional pain comes from is an effective, yet often forgotten intervention. Compassionate psychological counseling can have a powerful role in treatment.9

Big pharma’s Interest in Repurposing Psychedelics and Experimental Drugs for Mental Health

big pharma repurposes drugsBased on past performance and legal challenges from victims of dangerous psychiatric drugs, the most obvious driver for pharmaceutical drug companies appears to be making a profit, and avoiding bankruptcy if they can.

Hundreds of drug companies, both small and overpoweringly huge, went bust in recent years because their products were dangerous, and their marketing strategies were found to be intentionally misleading. In the case of nasal spray fentanyl, doctors were enticed with kickbacks, parties, and free lap dances to encourage them to prescribe to people who had no medical need for the drug.

The corrupt opioid market has been beaten back (a bit) by lawsuits and a somewhat more educated broad public. A growing awareness on the part of both doctors and patients has begun to take a second look at the drug industry as a whole.

The novel use of psychedelics such as intranasal ketamine for depression appears to be a desperate attempt to keep big pharma’s foothold on the precipice of staying in business. Sadly, there seems to be little to no interest, in any genuine sense, in the health of their customers.17

Known Factors Contributing to Psychiatric Symptoms

A growing body of research demonstrates there are multiple factors that can contribute to depression and other psychiatric symptoms. It may take time to evaluate a person’s unique history and current condition but this is needed to assess the most important of these to address, and to successfully resolve the problems.18

  • nutrition and diet
  • microbiome health
  • exposures to contaminants in water, air, food, chemicals from environmental sources
  • genetic factors
  • significant life events, i.e., exposure to hardship, trauma, loss
  • inflammation
  • risk behaviors, i.e., substance abuse, shift-work, job stress, sedentary lifestyle
  • chronic sleep deficits

Alternative Treatments Offered at ATMC for Mental Wellness

holistic mental health sedona drug rehabAlternative to Meds Center uses an extremely broad range of drug-free treatments for recovery of mental health symptoms that have persisted despite standard (or experimental) drug treatment. Where a person has found intranasal esketamine treatment unsatisfactory, or multiple medications, and desires to safely withdraw from these, the center offers specialized treatment programs to address the process in an orderly, comfortable way.

Please take some time to review the services offered at the center, so you can see the extensive range of treatment components that are used in designing a comprehensive individual treatment program.

For More Information

If you would like more information on our programs, including insurance coverage, costs, length of stay with us, or any other questions please contact us directly. A well-informed professional will speak with you and answer your questions. We are here to help. Find true recovery without the need for experimental drugs like intranasal esketamine for depression that didn’t help you transform and enjoy renewed natural mental health without drugs.


1. Janssen Health Professional Information ( Esketamine monograph Esketamine Product Monograph [approval 2020 May 19] [cited 2024 June 18]

2. (No authors listed) drugs. com Esketamine Monograph for Professionals [cited 2024 June 18]

3. FDA drug label SpravatoTM (esketamine nasal spray)  [approval 1970] [cited 2024 June 18]

4. FDA drug label Ketalar (ketamine hydrochloride injection) [tentatively approved as a new molecular entity 1970, label published March 2012] [cited 2024 June 18]

5. FDA Safety Alert FDA alerts health care professionals….ketamine nasal spray published online Feb.16 2022[cited 2024 June 18]

6. FDA Approved Risk Evaluation and Mitihation Strategies Spravato published 01/03/2022 [cited 2024 June 18]

7. d’Andrea G, Pettorruso M, Lorenzo GD, Mancusi G, McIntyre RS, Martinotti G. Rethinking ketamine and esketamine action: Are they antidepressants with mood-stabilizing properties? Eur Neuropsychopharmacol. 2023 May;70:49-55. doi: 10.1016/j.euroneuro.2023.02.010. Epub 2023 Mar 1. PMID: 36867895. [cited 2024 June 18]

8. Vasiliu O. Esketamine for treatment‑resistant depression: A review of clinical evidence (Review). Exp Ther Med. 2023 Jan 25;25(3):111. doi: 10.3892/etm.2023.11810. PMID: 36793329; PMCID: PMC9922941. [cited 2024 June 18]

9. Frontiers | Intranasal Esketamine and Current Suicidal Ideation With Intent in Major Depression Disorder: Beat the Clock, Save a Life, Start a Strategy  [cited 2024 June 18]

10. Seshadri A, Prokop LJ, Singh B. Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for Major depression: A systematic review and meta-analysis. J Affect Disord. 2024 Jul 1;356:379-384. doi: 10.1016/j.jad.2024.03.137. Epub 2024 Mar 26. PMID: 38537759. [cited 2024 June 18]

11. Baudot J, Soeiro T, Tambon M, Navarro N, Veyrac G, Mezaache S, Micallef J. Safety concerns on the abuse potential of esketamine: Multidimensional analysis of a new anti-depressive drug on the market. Fundam Clin Pharmacol. 2022 Jun;36(3):572-581. doi: 10.1111/fcp.12745. Epub 2021 Dec 23. PMID: 34907579. [cited 2024 June 18]

12. Ghaemi SN. Symptomatic versus disease-modifying effects of psychiatric drugs. Acta Psychiatr Scand. 2022 Sep;146(3):251-257. doi: 10.1111/acps.13459. Epub 2022 Jun 25. PMID: 35653111. [cited 2024 June 18]

13. Hengartner MP. Methodological flaws, conflicts of interest, and scientific fallacies: implications for the evaluation of antidepressants’ efficacy and harm. Front Psychiatry 2017; 8: 275. [cited 2024 June 18]

14. Fava GA. Rational use of antidepressant drugs. Psychother Psychosom 2014; >83: 197–204. [cited 2024 June 18]

15. Perlis RH.  Anxiety about antidepressants. Am J Psychiatry 2018; 175: 500–501. [cited 2024 June 18]

16. Ko Y, Cho YH, Kim GW, Hong CH, Son SJ, Roh HW, Moon J, Han S. Relationships of walking activity with depressed mood and suicidal ideation among the middle-aged Korean population: a nationwide cross-sectional study. Front Psychiatry. 2023 Sep 5;14:1202068. doi: 10.3389/fpsyt.2023.1202068. PMID: 37743985; PMCID: PMC10512318. [cited 2024 June 18]

17. Parrish M., 7 of the biggest pharma bankruptcies this year published online Pharma Manufacturing Magazine Sept 23, 2019 [cited 2024 June 18]

18. Remes O, Mendes JF, Templeton P. Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature. Brain Sci. 2021 Dec 10;11(12):1633. doi: 10.3390/brainsci11121633. PMID: 34942936; PMCID: PMC8699555. [cited 2024 June 18]

19. Jakobsen JC, Gluud C, Kirsch I. Should antidepressants be used for major depressive disorder? BMJ Evid Based Med. 2020 Aug;25(4):130. doi: 10.1136/bmjebm-2019-111238. Epub 2019 Sep 25. PMID: 31554608; PMCID: PMC7418603. [cited 2024 June 18]

20. Daly EJ, Turkoz I, Salvadore G, Fedgchin M, Ionescu DF, Starr HL, Borentain S, Trivedi MH, Thase ME, Singh JB. The effect of esketamine in patients with treatment-resistant depression with and without comorbid anxiety symptoms or disorder. Depress Anxiety. 2021 Nov;38(11):1120-1130. doi: 10.1002/da.23193. Epub 2021 Jul 22. PMID: 34293233; PMCID: PMC9291524. [cited 2024 June 18]

21. Dowrick C, Francis A,  Medicalizing Unhappiness: new classification of depression risks more patients being put on drug treatment from which they will not benefit BMJ 2013 [published online 09 December 2013] [cited 2024 June 18]

22. Baudot J, Soeiro T, Tambon M, Navarro N, Veyrac G, Mezaache S, Micallef J. Safety concerns on the abuse potential of esketamine: Multidimensional analysis of a new anti-depressive drug on the market. Fundam Clin Pharmacol. 2022 Jun;36(3):572-581. doi: 10.1111/fcp.12745. Epub 2021 Dec 23. PMID: 34907579. [cited 2024 June 19]

23. Kryst J, Kawalec P, Pilc A. Efficacy and safety of intranasal esketamine for the treatment of major depressive disorder. Expert Opin Pharmacother. 2020 Jan;21(1):9-20. doi: 10.1080/14656566.2019.1683161. Epub 2019 Oct 30. PMID: 31663783. [cited 2024 June 19]

Originally Published June 19, 2024 by Diane Ridaeus

This content has been reviewed and approved by a licensed physician.

Dr. Samuel Lee

Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente.  He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.

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