The Surprising Role of Ketamine in Combatting Depression: A Pharmacist's Insight

Table of ContentsView AllTable of ContentsKetamine Treatment for DepressionUnderstanding DepressionBenefits and RisksAccessing Ketamine Treatment

Table of ContentsView All

View All

Table of Contents

Ketamine Treatment for Depression

Understanding Depression

Benefits and Risks

Accessing Ketamine Treatment

Ketamineis an injectable anesthetic (a medicine that puts people to sleep during surgical procedures).Ketamine is related to the recreational drugphencyclidine(PCP).

Studies have found that low doses of ketamine can quickly reverse symptoms of depression.But so far, the U.S. Food and Drug Administration (FDA) has not approved it for depression or any other mental health condition.

Ketamineis taken off-label (meaning the FDA does not approve it) for depression that hasn’t responded to traditional antidepressants.This type of depression is known astreatment-resistant depression (TRD). About 30% of people with depression experience TRD.

Depressionis the most prevalent mental health condition in the United States.It affects over 8% of adults and nearly 20% of those between ages 18 and 25.

Depression is typically treated with psychotherapy (such as cognitive behavioral therapy or interpersonal therapy), antidepressant medications, or both.Some examples of antidepressant medications include but are not limited to Prozac (fluoxetine), Zoloft (sertraline), and Cymbalta (duloxetine).

Finding the proper treatment for it is crucial to improve daily life and prevent complications like suicide.

Benefits and Risks of Ketamine Treatment

Before starting ketamine treatment, there are some essential benefits and risks to be aware of, including:

Suicide Prevention HotlineIf you or someone you know are having suicidal thoughts, dial988to contact the988 Suicide & Crisis Lifelineand connect with a trained counselor. For more mental health resources, see ourNational Helpline Database.

Suicide Prevention Hotline

If you or someone you know are having suicidal thoughts, dial988to contact the988 Suicide & Crisis Lifelineand connect with a trained counselor. For more mental health resources, see ourNational Helpline Database.

There are several challenges associated with taking ketamine for depression, from finding a provider to affording the treatment. Here’s a closer look:

Summary

Ketamine is a medicine approved for surgical anesthesia. It is taken off-label for depression.

In contrast to other antidepressants, ketamine begins to work within hours. For this reason, it is a good option for people with severe depression or those with suicidal thoughts.

Ketamine is usually given as an IV infusion in a healthcare setting like a hospital or specialized clinic.

Keep in mind that ketamine is a Schedule III controlled substance in the U.S. and requires a prescription from a healthcare provider to be legal.

Serious side effects of ketamine include high blood pressure and heart rate, drowsiness, cognitive problems, and hallucinations or dissociation.

23 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Yavi M, Lee H, Henter ID, et al.Ketamine treatment for depression: a review.Discov Ment Health. 2022;2(1):9. doi:10.1007/s44192-022-00012-3Hess EM, Riggs LM, Michaelides M, et al.Mechanisms of ketamine and its metabolites as antidepressants.Biochem Pharmacol. 2022;197:114892. doi:10.1016/j.bcp.2021.114892U.S. Food and Drug Administration.FDA warns patients and health care providers about potential risks associated with compounded ketamine products, including oral formulations, for the treatment of psychiatric disorders.Jelen LA, Stone JM.Ketamine for depression.Int Rev Psychiatry. 2021;33(3):207-228. doi:10.1080/09540261.2020.1854194Parikh SV, Lopez D, Vande Voort JL, et al.Developing an IV ketamine clinic for treatment-resistant depression: a primer.Psychopharmacol Bull. 2021;51(3):109-124.Zhu W, Ding Z, Zhang Y, et al.Risks associated with misuse of ketamine as a rapid-acting antidepressant.Neurosci Bull. 2016;32(6):557-564. doi:10.1007/s12264-016-0081-2Adell A.Brain NMDA receptors in schizophrenia and depression.Biomolecules. 2020;10(6):947. Published 2020 Jun 23. doi:10.3390/biom10060947Peskin E, Gudin J, Schatman ME.Increased demand for ketamine infusions and associated complexities.J Pain Res. 2023;16:295-299. Published 2023 Jan 28. doi:10.2147/JPR.S403323Sobule R, Ithman M.Ketamine: studies show benefit.Mo Med. 2023;120(1):29-30.Rosenblat JD, Carvalho AF, Li M, et al.Oral ketamine for depression: a systematic review. 2020 Apr 22;81(2):20lcx13315. doi: 10.4088/JCP.20lcx13315].J Clin Psychiatry. 2019;80(3):18r12475. Published 2019 Apr 16. doi:10.4088/JCP.18r12475U.S. Food and Drug Administration.SPRAVATO™ (esketamine) nasal spray, CIII prescribing information.Kim JW, Suzuki K, Kavalali ET, et al.Ketamine: mechanisms and relevance to treatment of depression.Annu Rev Med. 2024;75:129-143. doi:10.1146/annurev-med-051322-120608Goodwin RD, Dierker LC, Wu M, et al.Trends in U.S. depression prevalence from 2015 to 2020: the widening treatment gap.Am J Prev Med. 2022;63(5):726-733. doi:10.1016/j.amepre.2022.05.014National Institute of Mental Health.Major depression.National Institute of Mental Health.Depression.Karrouri R, Hammani Z, Benjelloun R, et al.Major depressive disorder: validated treatments and future challenges.World J Clin Cases. 2021;9(31):9350-9367. doi:10.12998/wjcc.v9.i31.9350Department of Justice/ Drug Enforcement Administration Drug Fact Sheet.Ketamine.Alnefeesi Y, Chen-Li D, Krane E, et al.Real-world effectiveness of ketamine in treatment-resistant depression: a systematic review & meta-analysis.J Psychiatr Res. 2022;151:693-709. doi:10.1016/j.jpsychires.2022.04.037Veraart JKE, Smith-Apeldoorn SY, Spijker J, et al.Ketamine treatment for depression in patients with a history of psychosis or current psychotic symptoms: a systematic review.J Clin Psychiatry. 2021;82(4):20r13459. Published 2021 Jul 13. doi:10.4088/JCP.20r13459Murphy RJ, Muthukumaraswamy S, de Wit H.Microdosing psychedelics: current evidence from controlled studies.Biol Psychiatry Cogn Neurosci Neuroimaging. 2024;9(5):500-511. doi:10.1016/j.bpsc.2024.01.002Higgins GA, Carroll NK, Brown M, et al.Low doses of psilocybin and ketamine enhance motivation and attention in poor performing rats: evidence for an antidepressant property.Front Pharmacol. 2021;12:640241. Published 2021 Feb 26. doi:10.3389/fphar.2021.640241ASKP3.Directory.Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies.Neuropsychiatr Dis Treat. 2020;16:221-234. Published 2020 Jan 21. doi:10.2147/NDT.S198774

23 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Yavi M, Lee H, Henter ID, et al.Ketamine treatment for depression: a review.Discov Ment Health. 2022;2(1):9. doi:10.1007/s44192-022-00012-3Hess EM, Riggs LM, Michaelides M, et al.Mechanisms of ketamine and its metabolites as antidepressants.Biochem Pharmacol. 2022;197:114892. doi:10.1016/j.bcp.2021.114892U.S. Food and Drug Administration.FDA warns patients and health care providers about potential risks associated with compounded ketamine products, including oral formulations, for the treatment of psychiatric disorders.Jelen LA, Stone JM.Ketamine for depression.Int Rev Psychiatry. 2021;33(3):207-228. doi:10.1080/09540261.2020.1854194Parikh SV, Lopez D, Vande Voort JL, et al.Developing an IV ketamine clinic for treatment-resistant depression: a primer.Psychopharmacol Bull. 2021;51(3):109-124.Zhu W, Ding Z, Zhang Y, et al.Risks associated with misuse of ketamine as a rapid-acting antidepressant.Neurosci Bull. 2016;32(6):557-564. doi:10.1007/s12264-016-0081-2Adell A.Brain NMDA receptors in schizophrenia and depression.Biomolecules. 2020;10(6):947. Published 2020 Jun 23. doi:10.3390/biom10060947Peskin E, Gudin J, Schatman ME.Increased demand for ketamine infusions and associated complexities.J Pain Res. 2023;16:295-299. Published 2023 Jan 28. doi:10.2147/JPR.S403323Sobule R, Ithman M.Ketamine: studies show benefit.Mo Med. 2023;120(1):29-30.Rosenblat JD, Carvalho AF, Li M, et al.Oral ketamine for depression: a systematic review. 2020 Apr 22;81(2):20lcx13315. doi: 10.4088/JCP.20lcx13315].J Clin Psychiatry. 2019;80(3):18r12475. Published 2019 Apr 16. doi:10.4088/JCP.18r12475U.S. Food and Drug Administration.SPRAVATO™ (esketamine) nasal spray, CIII prescribing information.Kim JW, Suzuki K, Kavalali ET, et al.Ketamine: mechanisms and relevance to treatment of depression.Annu Rev Med. 2024;75:129-143. doi:10.1146/annurev-med-051322-120608Goodwin RD, Dierker LC, Wu M, et al.Trends in U.S. depression prevalence from 2015 to 2020: the widening treatment gap.Am J Prev Med. 2022;63(5):726-733. doi:10.1016/j.amepre.2022.05.014National Institute of Mental Health.Major depression.National Institute of Mental Health.Depression.Karrouri R, Hammani Z, Benjelloun R, et al.Major depressive disorder: validated treatments and future challenges.World J Clin Cases. 2021;9(31):9350-9367. doi:10.12998/wjcc.v9.i31.9350Department of Justice/ Drug Enforcement Administration Drug Fact Sheet.Ketamine.Alnefeesi Y, Chen-Li D, Krane E, et al.Real-world effectiveness of ketamine in treatment-resistant depression: a systematic review & meta-analysis.J Psychiatr Res. 2022;151:693-709. doi:10.1016/j.jpsychires.2022.04.037Veraart JKE, Smith-Apeldoorn SY, Spijker J, et al.Ketamine treatment for depression in patients with a history of psychosis or current psychotic symptoms: a systematic review.J Clin Psychiatry. 2021;82(4):20r13459. Published 2021 Jul 13. doi:10.4088/JCP.20r13459Murphy RJ, Muthukumaraswamy S, de Wit H.Microdosing psychedelics: current evidence from controlled studies.Biol Psychiatry Cogn Neurosci Neuroimaging. 2024;9(5):500-511. doi:10.1016/j.bpsc.2024.01.002Higgins GA, Carroll NK, Brown M, et al.Low doses of psilocybin and ketamine enhance motivation and attention in poor performing rats: evidence for an antidepressant property.Front Pharmacol. 2021;12:640241. Published 2021 Feb 26. doi:10.3389/fphar.2021.640241ASKP3.Directory.Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies.Neuropsychiatr Dis Treat. 2020;16:221-234. Published 2020 Jan 21. doi:10.2147/NDT.S198774

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Yavi M, Lee H, Henter ID, et al.Ketamine treatment for depression: a review.Discov Ment Health. 2022;2(1):9. doi:10.1007/s44192-022-00012-3Hess EM, Riggs LM, Michaelides M, et al.Mechanisms of ketamine and its metabolites as antidepressants.Biochem Pharmacol. 2022;197:114892. doi:10.1016/j.bcp.2021.114892U.S. Food and Drug Administration.FDA warns patients and health care providers about potential risks associated with compounded ketamine products, including oral formulations, for the treatment of psychiatric disorders.Jelen LA, Stone JM.Ketamine for depression.Int Rev Psychiatry. 2021;33(3):207-228. doi:10.1080/09540261.2020.1854194Parikh SV, Lopez D, Vande Voort JL, et al.Developing an IV ketamine clinic for treatment-resistant depression: a primer.Psychopharmacol Bull. 2021;51(3):109-124.Zhu W, Ding Z, Zhang Y, et al.Risks associated with misuse of ketamine as a rapid-acting antidepressant.Neurosci Bull. 2016;32(6):557-564. doi:10.1007/s12264-016-0081-2Adell A.Brain NMDA receptors in schizophrenia and depression.Biomolecules. 2020;10(6):947. Published 2020 Jun 23. doi:10.3390/biom10060947Peskin E, Gudin J, Schatman ME.Increased demand for ketamine infusions and associated complexities.J Pain Res. 2023;16:295-299. Published 2023 Jan 28. doi:10.2147/JPR.S403323Sobule R, Ithman M.Ketamine: studies show benefit.Mo Med. 2023;120(1):29-30.Rosenblat JD, Carvalho AF, Li M, et al.Oral ketamine for depression: a systematic review. 2020 Apr 22;81(2):20lcx13315. doi: 10.4088/JCP.20lcx13315].J Clin Psychiatry. 2019;80(3):18r12475. Published 2019 Apr 16. doi:10.4088/JCP.18r12475U.S. Food and Drug Administration.SPRAVATO™ (esketamine) nasal spray, CIII prescribing information.Kim JW, Suzuki K, Kavalali ET, et al.Ketamine: mechanisms and relevance to treatment of depression.Annu Rev Med. 2024;75:129-143. doi:10.1146/annurev-med-051322-120608Goodwin RD, Dierker LC, Wu M, et al.Trends in U.S. depression prevalence from 2015 to 2020: the widening treatment gap.Am J Prev Med. 2022;63(5):726-733. doi:10.1016/j.amepre.2022.05.014National Institute of Mental Health.Major depression.National Institute of Mental Health.Depression.Karrouri R, Hammani Z, Benjelloun R, et al.Major depressive disorder: validated treatments and future challenges.World J Clin Cases. 2021;9(31):9350-9367. doi:10.12998/wjcc.v9.i31.9350Department of Justice/ Drug Enforcement Administration Drug Fact Sheet.Ketamine.Alnefeesi Y, Chen-Li D, Krane E, et al.Real-world effectiveness of ketamine in treatment-resistant depression: a systematic review & meta-analysis.J Psychiatr Res. 2022;151:693-709. doi:10.1016/j.jpsychires.2022.04.037Veraart JKE, Smith-Apeldoorn SY, Spijker J, et al.Ketamine treatment for depression in patients with a history of psychosis or current psychotic symptoms: a systematic review.J Clin Psychiatry. 2021;82(4):20r13459. Published 2021 Jul 13. doi:10.4088/JCP.20r13459Murphy RJ, Muthukumaraswamy S, de Wit H.Microdosing psychedelics: current evidence from controlled studies.Biol Psychiatry Cogn Neurosci Neuroimaging. 2024;9(5):500-511. doi:10.1016/j.bpsc.2024.01.002Higgins GA, Carroll NK, Brown M, et al.Low doses of psilocybin and ketamine enhance motivation and attention in poor performing rats: evidence for an antidepressant property.Front Pharmacol. 2021;12:640241. Published 2021 Feb 26. doi:10.3389/fphar.2021.640241ASKP3.Directory.Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies.Neuropsychiatr Dis Treat. 2020;16:221-234. Published 2020 Jan 21. doi:10.2147/NDT.S198774

Yavi M, Lee H, Henter ID, et al.Ketamine treatment for depression: a review.Discov Ment Health. 2022;2(1):9. doi:10.1007/s44192-022-00012-3

Hess EM, Riggs LM, Michaelides M, et al.Mechanisms of ketamine and its metabolites as antidepressants.Biochem Pharmacol. 2022;197:114892. doi:10.1016/j.bcp.2021.114892

U.S. Food and Drug Administration.FDA warns patients and health care providers about potential risks associated with compounded ketamine products, including oral formulations, for the treatment of psychiatric disorders.

Jelen LA, Stone JM.Ketamine for depression.Int Rev Psychiatry. 2021;33(3):207-228. doi:10.1080/09540261.2020.1854194

Parikh SV, Lopez D, Vande Voort JL, et al.Developing an IV ketamine clinic for treatment-resistant depression: a primer.Psychopharmacol Bull. 2021;51(3):109-124.

Zhu W, Ding Z, Zhang Y, et al.Risks associated with misuse of ketamine as a rapid-acting antidepressant.Neurosci Bull. 2016;32(6):557-564. doi:10.1007/s12264-016-0081-2

Adell A.Brain NMDA receptors in schizophrenia and depression.Biomolecules. 2020;10(6):947. Published 2020 Jun 23. doi:10.3390/biom10060947

Peskin E, Gudin J, Schatman ME.Increased demand for ketamine infusions and associated complexities.J Pain Res. 2023;16:295-299. Published 2023 Jan 28. doi:10.2147/JPR.S403323

Sobule R, Ithman M.Ketamine: studies show benefit.Mo Med. 2023;120(1):29-30.

Rosenblat JD, Carvalho AF, Li M, et al.Oral ketamine for depression: a systematic review. 2020 Apr 22;81(2):20lcx13315. doi: 10.4088/JCP.20lcx13315].J Clin Psychiatry. 2019;80(3):18r12475. Published 2019 Apr 16. doi:10.4088/JCP.18r12475

U.S. Food and Drug Administration.SPRAVATO™ (esketamine) nasal spray, CIII prescribing information.

Kim JW, Suzuki K, Kavalali ET, et al.Ketamine: mechanisms and relevance to treatment of depression.Annu Rev Med. 2024;75:129-143. doi:10.1146/annurev-med-051322-120608

Goodwin RD, Dierker LC, Wu M, et al.Trends in U.S. depression prevalence from 2015 to 2020: the widening treatment gap.Am J Prev Med. 2022;63(5):726-733. doi:10.1016/j.amepre.2022.05.014

National Institute of Mental Health.Major depression.

National Institute of Mental Health.Depression.

Karrouri R, Hammani Z, Benjelloun R, et al.Major depressive disorder: validated treatments and future challenges.World J Clin Cases. 2021;9(31):9350-9367. doi:10.12998/wjcc.v9.i31.9350

Department of Justice/ Drug Enforcement Administration Drug Fact Sheet.Ketamine.

Alnefeesi Y, Chen-Li D, Krane E, et al.Real-world effectiveness of ketamine in treatment-resistant depression: a systematic review & meta-analysis.J Psychiatr Res. 2022;151:693-709. doi:10.1016/j.jpsychires.2022.04.037

Veraart JKE, Smith-Apeldoorn SY, Spijker J, et al.Ketamine treatment for depression in patients with a history of psychosis or current psychotic symptoms: a systematic review.J Clin Psychiatry. 2021;82(4):20r13459. Published 2021 Jul 13. doi:10.4088/JCP.20r13459

Murphy RJ, Muthukumaraswamy S, de Wit H.Microdosing psychedelics: current evidence from controlled studies.Biol Psychiatry Cogn Neurosci Neuroimaging. 2024;9(5):500-511. doi:10.1016/j.bpsc.2024.01.002

Higgins GA, Carroll NK, Brown M, et al.Low doses of psilocybin and ketamine enhance motivation and attention in poor performing rats: evidence for an antidepressant property.Front Pharmacol. 2021;12:640241. Published 2021 Feb 26. doi:10.3389/fphar.2021.640241

ASKP3.Directory.

Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies.Neuropsychiatr Dis Treat. 2020;16:221-234. Published 2020 Jan 21. doi:10.2147/NDT.S198774

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