Ketamine for Treatment-Resistant Depression

Table of ContentsView AllTable of ContentsWhat Treatment-Resistant Depression IsHow Ketamine HelpsConcerns About KetamineFactors to Consider Before UseTakeaways

Table of ContentsView All

View All

Table of Contents

What Treatment-Resistant Depression Is

How Ketamine Helps

Concerns About Ketamine

Factors to Consider Before Use

Takeaways

Close

Almost one in three people with major depressive disorder—also referred to asclinical depression—don’t find relief from standard treatment methods.This is referred to as havingtreatment-resistant depression. If you have treatment-resistant depression, your doctor may recommend ketamine as a treatment option.

Research indicates that ketamine can help with treatment-resistant depression, at least in the short term.However, this drug doesn’t come without its challenges, including its adverse side effects and the potential for addiction.

At a GlanceAntidepressants are an important tool for treating depression, but they don’t work for everyone. Some people continue to experience symptoms even after trying more than two types of antidepressants, which is why your doctor might suggest ketamine as an option for treatment-resistant depression. Ketamine is a type of dissociative medication that affects certain receptors in the brain, leading to depersonalization effects and a rapid reduction in depressive symptoms. However, it is important to note that ketamine can have risks, including a potential for misuse. Before you decide if it’s right for you, talk to your doctor about your options and only go to a doctor or therapist that offers comprehensive evaluation, support, and supervision during treatment.

At a Glance

Antidepressants are an important tool for treating depression, but they don’t work for everyone. Some people continue to experience symptoms even after trying more than two types of antidepressants, which is why your doctor might suggest ketamine as an option for treatment-resistant depression. Ketamine is a type of dissociative medication that affects certain receptors in the brain, leading to depersonalization effects and a rapid reduction in depressive symptoms. However, it is important to note that ketamine can have risks, including a potential for misuse. Before you decide if it’s right for you, talk to your doctor about your options and only go to a doctor or therapist that offers comprehensive evaluation, support, and supervision during treatment.

What Is Treatment-Resistant Depression?

While experts don’t always agree on how to definetreatment-resistant depression, most use this term to describe when a person has tried at least two traditionaldepression treatments(such as psychotherapy and antidepressants), but failed to achieve positive results after a reasonable amount of time.

To be clear, this doesn’t mean that depression isn’ttreatable. It simply says that a person’s symptoms don’t improve with standard treatment methods. In cases such as these, bothelectroconvulsive therapy(ECT) andtranscranial magnetic stimulation(TMS) can both help. The problem is that they may not provide relief for several weeks.

This can be discouraging if you’re the one with treatment-resistant depression, making you wonder if your feelings will ever go away. It may also help explain why people with treatment-resistant depression have a higher risk of abusing alcohol and drugs, and an increased suicide risk.

Suicide Prevention HotlineIf you or a loved one are having thoughts of suicide, call 911 immediately or call theNational Suicide Prevention Lifelineat988. For more mental health resources, see ourNational Helpline Database.

Suicide Prevention Hotline

If you or a loved one are having thoughts of suicide, call 911 immediately or call theNational Suicide Prevention Lifelineat988. For more mental health resources, see ourNational Helpline Database.

Ketamine is a medication-based option for treatment-resistant depression that, unlike ECT and TMS, doesn’t require the use of specialized devices. Ketamine also offers patients faster relief, sometimes easing depression after just a single dose (especially if used intravenously).

Causes of Treatment-Resistant Depression

How Ketamine Helps Treatment-Resistant Depression

Ketamineis a dissociative anesthetic, meaning that it can make you feel detached from your environment while also easing pain. Some research suggests that it is through dissociation that people with treatment-resistant depression find relief, in part, through inducing depersonalization.

Other studies say that it is ketamine’s effect on certain receptors in the brain that is responsible for its positive results. Specifically, ketamine is an N-methyl-D-aspartate receptor antagonist and, in this role, provides “rapid antidepressant effects” in people with treatment-resistant depression.

Another study looked at the effectiveness of oral ketamine. This one involved 22 patients who had tried at least three differentantidepressant treatmentswith no effect. Almost one in three (30%) reported that ketamine provided some benefit.

Concerns About Ketamine for Treatment-Resistant Depression

Based on its ability to help ease hard-to-treat depression, it’s easy to see why ketamine may be prescribed. Yet, there are a few concerns that exist with this drug.

Illegal Ketamine Use Is on the Rise

Using any drug without a prescription can be harmful if not dangerous to one’s health. Obtaining ketamine illegally can also unknowingly expose users to other drugs as it is often found in combination with MDMA (ecstasy), amphetamines, methamphetamines, and cocaine.

Potential for Ketamine Misuse

Since ketamine is a Schedule III controlled substance, it has less potential for abuse than Schedule I and II drugs, but some potential does still exist. Additionally, the abuse of a Schedule III substance can lead to physical and/or psychological dependence.

In addition to developing a ketamine addiction, misuse can also lead to accidentaloverdose—a situation that can occur due to underestimating the potency of this drug.While death from overdose is rare,misusing the drug can still be harmful to the body and mind.

Ketamine’s Adverse Side Effects

Another concern of using ketamine for treatment-resistant depression is that users can experience a variety of negative side effects. One of the most common immediate effects of taking ketamine is feeling strange, weird, or loopy.

Because ketamine can produce feelings of dissociation, people taking higher doses of this drug might also experience what is known as a “k-hole.” This is when you feel completely disconnected from your body, such as in an out-of-body experience, and may have limited to no control over your speech and movements.

This drug also has other effects as well. Short-term side effects of ketamine use can include:

Long-term consequences of using ketamine include experiencing physical issues such as bladder ulcers and pain, kidney problems, and stomach pain, along with having mental health issues related to depression, experiencing flashbacks, and poor memory.

I Tried It: At-Home Ketamine Therapy

Factors to Consider Before Using Ketamine for Depression

Ketamine can be effective for treating depression that doesn’t respond to standard treatment methods. However, knowing the concerns surrounding ketamine for treatment-resistant depression is only the first step in deciding whether it’s the right option for you.

It’s also important to consider how you obtain your ketamine. Getting a prescription from your healthcare provider or a mental health professional can help ensure that the drug is safe based on your health status and condition. This is just one area where some ketamine clinics fall short.

Ketamine clinics offer access to this drug in the name of wellness. However, research has found that these clinics vary widely, with many not performing comprehensive enough evaluations, inadequately communicating ketamine’s effects, and failing to provide the appropriate medical and psychological support during treatment.

For these reasons, it’s best to speak with your healthcare team if you are considering ketamine for your depression. Your healthcare provider or mental health therapist can help you decide if it is the best treatment for you based on scientifically supported evidence and your specific diagnosis and situation.

Ketamine shows promise in the treatment of a variety of mental health conditions, including depression and other mood disorders. It may be particularly effective when used to help people with treatment-resistant depression. Like all treatments, you should talk to your doctor to determine if this option is right for you.

What Are the Different Types of Ketamine Treatment?

18 SourcesVerywell Mind 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.Zhdanava M, Pilon D, Ghelerter I, et al.The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States.J Clin Psychiatry. 2021;82(2):20m13699. doi:10.4088/JCP.20m13699Lent JK, Arredondo A, Pugh MA, Austin PN.Ketamine and treatment-resistant depression.AANA J. 2019;87(5):411-419.Gaynes BN, Lux L, Gartlehner G, et al.Defining treatment-resistant depression.Depress Anxiety. 2019;37(2):134-145. doi:10.1002/da.22968Fava M, Freeman MP, Flynn M, et al.Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD).Molecular Psychiatry. 2020;25:1592-1603. doi:10.1038/s41380-018-0256-5Niciu MJ, Shovestul BJ, Jaso BA, et al.Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.J Affect Disord. 2018;232:310-315. doi:10.1016/j.jad.2018.02.049Serafini G, Howland RH, Rovedi F, Girardi P, Amore M.The role of ketamine in treatment-resistant depression: A systematic review.Curr Neuropharmacol. 2014;12(5):444-461. doi:10.2174/1570159X12666140619204251Phillips JL, Norris S, Talbot J, et al.Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: A randomized controlled trial.Am J Psychiatry. 2019;176(5):401-409. doi:10.1176/appi.ajp.2018.18070834Al Shirawi MI, Kennedy SH, Ho KT, Byrne R, Downar J.Oral ketamine in treatment-resistant depression.J Clin Psychopharmacol. 2017;37(4):464-467. doi:10.1097/JCP.0000000000000717U.S. Food and Drug Administration.FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.Palamar JJ, Rutherford C, Keyes KM.Trends in ketamine use, exposures, and seizures in the United States up to 2019.AJPH. 2021;111(11):2046-2049. doi:10.2105/AJPH.2021.306486Department of Justice, Drug Enforcement Administration.Drug fact sheet: Ketamine.U.S. Department of Justice.Ketamine fast facts.Cheng WJ, Chen CH, Chen CK, et al.Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia.Schizophren Res. 2018;199:313-318. doi:10.1016/j.schres.2018.02.049Maloney WJ.The health effects of the abuse of ketamine.Int J Depress Anxiety. 2018;1:006. doi:10.23937/ijda-2017/1710006Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M.A review of ketamine abuse and diversion.Depress Anxiety. 2016;33(8):718-727. doi:10.1002/da.22536Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, et al.Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression.J Affect Disord. 2020;263:568-575. doi:10.1016/j.jad.2019.11.028U.S. Department of Health and Human Services.Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health [Internet].Mathai DS, Lee SM, Mora V, O’Donnell KC, Garcia-Romeu A, Storch EA.Mapping consent practices for outpatient psychiatric use of ketamine.J Affect Disord. 2022;312:113-121. doi:10.1016/j.jad.2022.06.036

18 Sources

Verywell Mind 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.Zhdanava M, Pilon D, Ghelerter I, et al.The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States.J Clin Psychiatry. 2021;82(2):20m13699. doi:10.4088/JCP.20m13699Lent JK, Arredondo A, Pugh MA, Austin PN.Ketamine and treatment-resistant depression.AANA J. 2019;87(5):411-419.Gaynes BN, Lux L, Gartlehner G, et al.Defining treatment-resistant depression.Depress Anxiety. 2019;37(2):134-145. doi:10.1002/da.22968Fava M, Freeman MP, Flynn M, et al.Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD).Molecular Psychiatry. 2020;25:1592-1603. doi:10.1038/s41380-018-0256-5Niciu MJ, Shovestul BJ, Jaso BA, et al.Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.J Affect Disord. 2018;232:310-315. doi:10.1016/j.jad.2018.02.049Serafini G, Howland RH, Rovedi F, Girardi P, Amore M.The role of ketamine in treatment-resistant depression: A systematic review.Curr Neuropharmacol. 2014;12(5):444-461. doi:10.2174/1570159X12666140619204251Phillips JL, Norris S, Talbot J, et al.Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: A randomized controlled trial.Am J Psychiatry. 2019;176(5):401-409. doi:10.1176/appi.ajp.2018.18070834Al Shirawi MI, Kennedy SH, Ho KT, Byrne R, Downar J.Oral ketamine in treatment-resistant depression.J Clin Psychopharmacol. 2017;37(4):464-467. doi:10.1097/JCP.0000000000000717U.S. Food and Drug Administration.FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.Palamar JJ, Rutherford C, Keyes KM.Trends in ketamine use, exposures, and seizures in the United States up to 2019.AJPH. 2021;111(11):2046-2049. doi:10.2105/AJPH.2021.306486Department of Justice, Drug Enforcement Administration.Drug fact sheet: Ketamine.U.S. Department of Justice.Ketamine fast facts.Cheng WJ, Chen CH, Chen CK, et al.Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia.Schizophren Res. 2018;199:313-318. doi:10.1016/j.schres.2018.02.049Maloney WJ.The health effects of the abuse of ketamine.Int J Depress Anxiety. 2018;1:006. doi:10.23937/ijda-2017/1710006Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M.A review of ketamine abuse and diversion.Depress Anxiety. 2016;33(8):718-727. doi:10.1002/da.22536Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, et al.Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression.J Affect Disord. 2020;263:568-575. doi:10.1016/j.jad.2019.11.028U.S. Department of Health and Human Services.Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health [Internet].Mathai DS, Lee SM, Mora V, O’Donnell KC, Garcia-Romeu A, Storch EA.Mapping consent practices for outpatient psychiatric use of ketamine.J Affect Disord. 2022;312:113-121. doi:10.1016/j.jad.2022.06.036

Verywell Mind 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.

Zhdanava M, Pilon D, Ghelerter I, et al.The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States.J Clin Psychiatry. 2021;82(2):20m13699. doi:10.4088/JCP.20m13699Lent JK, Arredondo A, Pugh MA, Austin PN.Ketamine and treatment-resistant depression.AANA J. 2019;87(5):411-419.Gaynes BN, Lux L, Gartlehner G, et al.Defining treatment-resistant depression.Depress Anxiety. 2019;37(2):134-145. doi:10.1002/da.22968Fava M, Freeman MP, Flynn M, et al.Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD).Molecular Psychiatry. 2020;25:1592-1603. doi:10.1038/s41380-018-0256-5Niciu MJ, Shovestul BJ, Jaso BA, et al.Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.J Affect Disord. 2018;232:310-315. doi:10.1016/j.jad.2018.02.049Serafini G, Howland RH, Rovedi F, Girardi P, Amore M.The role of ketamine in treatment-resistant depression: A systematic review.Curr Neuropharmacol. 2014;12(5):444-461. doi:10.2174/1570159X12666140619204251Phillips JL, Norris S, Talbot J, et al.Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: A randomized controlled trial.Am J Psychiatry. 2019;176(5):401-409. doi:10.1176/appi.ajp.2018.18070834Al Shirawi MI, Kennedy SH, Ho KT, Byrne R, Downar J.Oral ketamine in treatment-resistant depression.J Clin Psychopharmacol. 2017;37(4):464-467. doi:10.1097/JCP.0000000000000717U.S. Food and Drug Administration.FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.Palamar JJ, Rutherford C, Keyes KM.Trends in ketamine use, exposures, and seizures in the United States up to 2019.AJPH. 2021;111(11):2046-2049. doi:10.2105/AJPH.2021.306486Department of Justice, Drug Enforcement Administration.Drug fact sheet: Ketamine.U.S. Department of Justice.Ketamine fast facts.Cheng WJ, Chen CH, Chen CK, et al.Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia.Schizophren Res. 2018;199:313-318. doi:10.1016/j.schres.2018.02.049Maloney WJ.The health effects of the abuse of ketamine.Int J Depress Anxiety. 2018;1:006. doi:10.23937/ijda-2017/1710006Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M.A review of ketamine abuse and diversion.Depress Anxiety. 2016;33(8):718-727. doi:10.1002/da.22536Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, et al.Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression.J Affect Disord. 2020;263:568-575. doi:10.1016/j.jad.2019.11.028U.S. Department of Health and Human Services.Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health [Internet].Mathai DS, Lee SM, Mora V, O’Donnell KC, Garcia-Romeu A, Storch EA.Mapping consent practices for outpatient psychiatric use of ketamine.J Affect Disord. 2022;312:113-121. doi:10.1016/j.jad.2022.06.036

Zhdanava M, Pilon D, Ghelerter I, et al.The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States.J Clin Psychiatry. 2021;82(2):20m13699. doi:10.4088/JCP.20m13699

Lent JK, Arredondo A, Pugh MA, Austin PN.Ketamine and treatment-resistant depression.AANA J. 2019;87(5):411-419.

Gaynes BN, Lux L, Gartlehner G, et al.Defining treatment-resistant depression.Depress Anxiety. 2019;37(2):134-145. doi:10.1002/da.22968

Fava M, Freeman MP, Flynn M, et al.Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD).Molecular Psychiatry. 2020;25:1592-1603. doi:10.1038/s41380-018-0256-5

Niciu MJ, Shovestul BJ, Jaso BA, et al.Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.J Affect Disord. 2018;232:310-315. doi:10.1016/j.jad.2018.02.049

Serafini G, Howland RH, Rovedi F, Girardi P, Amore M.The role of ketamine in treatment-resistant depression: A systematic review.Curr Neuropharmacol. 2014;12(5):444-461. doi:10.2174/1570159X12666140619204251

Phillips JL, Norris S, Talbot J, et al.Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: A randomized controlled trial.Am J Psychiatry. 2019;176(5):401-409. doi:10.1176/appi.ajp.2018.18070834

Al Shirawi MI, Kennedy SH, Ho KT, Byrne R, Downar J.Oral ketamine in treatment-resistant depression.J Clin Psychopharmacol. 2017;37(4):464-467. doi:10.1097/JCP.0000000000000717

U.S. Food and Drug Administration.FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.

Palamar JJ, Rutherford C, Keyes KM.Trends in ketamine use, exposures, and seizures in the United States up to 2019.AJPH. 2021;111(11):2046-2049. doi:10.2105/AJPH.2021.306486

Department of Justice, Drug Enforcement Administration.Drug fact sheet: Ketamine.

U.S. Department of Justice.Ketamine fast facts.

Cheng WJ, Chen CH, Chen CK, et al.Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia.Schizophren Res. 2018;199:313-318. doi:10.1016/j.schres.2018.02.049

Maloney WJ.The health effects of the abuse of ketamine.Int J Depress Anxiety. 2018;1:006. doi:10.23937/ijda-2017/1710006

Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M.A review of ketamine abuse and diversion.Depress Anxiety. 2016;33(8):718-727. doi:10.1002/da.22536

Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, et al.Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression.J Affect Disord. 2020;263:568-575. doi:10.1016/j.jad.2019.11.028

U.S. Department of Health and Human Services.Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health [Internet].

Mathai DS, Lee SM, Mora V, O’Donnell KC, Garcia-Romeu A, Storch EA.Mapping consent practices for outpatient psychiatric use of ketamine.J Affect Disord. 2022;312:113-121. doi:10.1016/j.jad.2022.06.036

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