Ketamine for Bipolar Disorder

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Medically reviewed: Paloma Lehfeldt, MD
a man who uses ketamine to help manage bipolar disorder

Ketamine-Assisted Therapy Could Help You Manage Bipolar Disorder Symptoms

Ketamine was synthesized in 1962 as part of an effort to create a safe and effective anesthetic that could be used in situations where a patient may be at risk for respiratory failure.(1) After clinical studies confirmed that ketamine was an effective sedative, anesthetic, and analgesic (pain reliever), it became widely utilized for surgical procedures.(2)

Ketamine is still expansively used today in human and veterinary medicine, largely because it has minimal side effects and a low risk for respiratory or cardiac complications, unlike other anesthetics.(2) When taking ketamine, people report out-of-body experiences (i.e., feelings of “having no limbs” or “floating in space”), vivid dreams, and changes in sensory perception.(3) This is known as dissociation, making ketamine a dissociative anesthetic.(1-3)

While medical providers primarily use ketamine as an anesthetic, they have also begun exploring its therapeutic potential for psychiatric conditions.(2) After several decades of research, ketamine has recently gained traction as a treatment option for depressive disorders, including bipolar depression, which is a component of bipolar disorder that is also referred to as depressive episodes, a phase of both bipolar 1 and 2 disorder.(1,2,4,5)

Ketamine may benefit you if you are at risk for suicide or actively experiencing a depressive episode.(6) Like other medications used to treat bipolar depression, ketamine treatment may exacerbate symptoms of mania in some people..(4,6)

What is Bipolar Disorder?

Bipolar and related disorders are a group of mental health conditions that devastate an individual’s quality of life and functionality.

People with bipolar and related disorders experience changes in mood, challenges in social or work settings, and sleep disturbances.(7) The DSM-5, which is a guidebook used by healthcare clinicians to diagnose mental health disorders, describes bipolar and related diagnoses:

  • Bipolar I Disorder: At least one present or past manic episode with or without a history of hypomanic (i.e., a milder form of mania) or major depressive episode(s).(7)
  • Bipolar II Disorder: Present or past hypomanic episode with a history of a major depressive episode(s).(7) Cyclothymic Disorder – Numerous experiences of fluctuating hypomanic and depressive symptoms that do not meet the criteria for full episodes.(7) 
  • Cyclothymic Disorder: Numerous experiences of fluctuating hypomanic and depressive symptoms that do not meet the criteria for full episodes.(7)

Bipolar disorder is often misdiagnosed as a major depressive disorder until manic (bipolar 1) or hypomanic symptoms (bipolar 2) also occur; therefore, treatment is frequently delayed.(8) Even with a proper diagnosis, many bipolar patients struggle with debilitating medication side effects, such as kidney and thyroid dysfunction, that may result in the decision to stop medical treatment. Some patients may also experience weight gain and lethargy while taking mood stabilizers.(9)

Mania and hypomania are defined as:

  • Mania: a period of at least a week of elevated mood, increase in energy, that interferes with a person’s ability to function in daily life, and can lead to hospitalization
  • Hypomania: at least four days of the same criteria as mania but does not require hospitalization and does not include psychotic symptoms.

What Are the Symptoms of Bipolar Disorder?The symptoms associated with bipolar and related disorders may vary depending upon the specific diagnosis but can include: mania, hypomania, and depressive experiences or episodes.

Symptoms of mania or hypomania may include:(7)

  • Excessive mood elevation and increased energy
  • Reduced need for sleep
  • Inflated self-esteem
  • Inflated self-esteem
  • Grandiose ideas, thoughts, or delusions
  • Impulsive behavior

Symptoms of depression may include:(7)

  • Feelings of Sadness or Hopelessness
  • Insomnia or Hypersomnia
  • Sudden Unexplained Weight Loss
  • Little Interest or Pleasure in Activities You Usually Enjoy
  • Thoughts of Death, Dying, or Suicide

If you are experiencing any of the symptoms above, including thoughts of suicide, you are not alone. A conversation with your healthcare provider can help you determine the right treatment option for you.

What Causes Bipolar Disorder?

The exact cause of bipolar disorder varies, and the underlying mechanisms are not fully understood. Like many mental health conditions, genetic and environmental factors (parental substance abuse during pregnancy, physical and psychological stress, loss of parents or loved ones, etc.) may play a role in the development and onset of illness.(10)

What is Ketamine Therapy for Bipolar Depression?

Ketamine treatment for bipolar depression can be administered in combination with different types of therapy, including cognitive behavioral therapy and mindfulness-based interventions (meditation, yoga, and awareness training).(11) The schedule of ketamine administration can vary across healthcare providers and individual treatment responses. Treatment may involve a single dose or multiple doses depending on symptom severity, and therapy sessions may occur before, during, or after receiving ketamine.(11-13)

It is important to note that ketamine is currently only used to help manage the symptoms of bipolar depression. To date, researchers have not seen success in exploring ketamine as a treatment for bipolar disorder as a whole. Early research indicates that ketamine may trigger manic episodes in some patients, making it less than ideal for treating the condition.

However, medical professionals have seen some promising results for using ketamine to manage the depressive phase of bipolar disorder, also known as bipolar depression.

a woman participating in ketamine therapy for bipolar depression

How Does Ketamine Help to Treat Bipolar Disorder?In the brain, ketamine acts on the N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor.(2) Glutamatergic activity in the brain, along with other types of neurotransmission (e.g., serotonin), is dysregulated in unipolar and bipolar depression. This means that your brain has unbalanced or poorly regulated levels of glutamate and other neurotransmitters available. 

This dysregulation of the glutamate system may be partially responsible for some bipolar symptoms.(10) The exact mechanism by which ketamine exerts anti-depressant effects in bipolar depression is not yet fully understood.(4) However, one recent study has shown that ketamine infusions can have a response and remission rates as high as 73% and 63%, respectively. In other words, ketamine may be highly effective for treating bipolar depression.
In addition to the direct action on brain chemistry, researchers speculate that subjective out-of-body experiences elicited by ketamine may be necessary to achieve full therapeutic potential.(14,15) For example, studies have found that more intense experiences of altered consciousness are associated with improvement in symptoms from unipolar and bipolar depression.(14

These altered states, which are also often described as “spiritual” and “mind-expanding,” may provide a promising comprehensive treatment option for bipolar depression. Some patients feel that these non-ordinary states of consciousness help them gain separation and objectivity when addressing particular aspects of their condition during therapy. 

How is Ketamine Administered for Bipolar Disorder?Ketamine can be administered in several ways, but the most common routes of administration in therapy settings include: (2,11)

IV-Intravenous ketamine administration for bipolar disorder
IV-Intravenous ketamine administration for bipolar disorder
Sublingual or oral lozenge ketamine administration for bipolar disorder
or Oral Lozenge
Nasal spray ketamine administration for bipolar disorder
Nasal Spray

Ketamine treatment sessions typically occur in a clinical setting where vital signs, consciousness, and responsiveness can be monitored if you have adverse physical or behavioral reactions.(16)

At-home ketamine treatments are also available. Many initial qualifying steps for at-home-based ketamine will be similar to outpatient treatments. For example, you will have a consultation and initial patient intake, and you will meet virtually with a provider to help you understand if ketamine is right for you.

Does Ketamine Carry Risks for People with Bipolar Disorder?Treatment with antidepressants for bipolar depression can carry the risk of causing a switch from depression to mania in some people. The risk of inducing mania or manic symptoms can vary based on antidepressant type (e.g., selective serotonin reuptake inhibitor) and individual factors (i.e., stress, genetics, substance use disorder).(17) However, the risk may be decreased if you also take mood stabilizers.(4,17)

Because evidence is lacking regarding ketamine efficacy for the manic symptoms of bipolar 1, current guidelines do not have explicit recommendations for or against using ketamine for bipolar mania.(16,18) This may be confusing, as some research, cited throughout, supports the use of ketamine for bipolar depression. If you are primarily experiencing symptoms of mania or hypomania, standard medications for bipolar mania (i.e., antipsychotics, anticonvulsants)(19) may be a better treatment option for you.

Could Ketamine Help Manage Your Bipolar Disorder Symptoms?Ketamine is a promising treatment option for bipolar depression, particularly in treatment-resistant and severe cases.(6) If you are experiencing severe depression or suicidal thoughts, treatment with ketamine may provide short-term but rapid relief.(4)

Compared to most traditional antidepressants, which can take several weeks,(20) ketamine may be able to help you as quickly as one day after treatment. Talk to your healthcare provider to determine whether ketamine therapy can help you find the relief you deserve from your symptoms of bipolar depression. If you’re interested, we can help find ketamine for bipolar depression near you.

Sources Cited

  1. Mion, G. (2017). History of anesthesia: The ketamine story–past, present and future. European Journal of Anaesthesiology, 34(9), 571-575.
  2.  Li, L., & Vlisides, P. E. (2016). Ketamine: 50 years of modulating the mind. Frontiers in human neuroscience, 10, 612.
  3. Domino, E. F., Chodoff, P., & Corssen, G. (1965). Pharmacologic effects of CI‐581, a new dissociative anesthetic, in man. Clinical Pharmacology & Therapeutics, 6(3), 279-291.
  4.  Wilkowska, A., Szałach, Ł., & Cubała, W. J. (2020). Ketamine in bipolar disorder: a review. Neuropsychiatric disease and treatment, 16, 2707.
  5. Bahji, A., Zarate Jr, C. A., & Vazquez, G. H. (2021). Ketamine for bipolar depression: a systematic review. International Journal of Neuropsychopharmacology, 24(7), 535-541.
  6. Kritzer, M. D., Mischel, N. A., Young, J. R., Lai, C. S., Masand, P. S., Szabo, S. T., & Mathew, S. J. (2022). Ketamine for treatment of mood disorders and suicidality: a narrative review of recent progress. Annals of clinical psychiatry: official journal of the American Academy of Clinical Psychiatrists, 34(1), 33.
  7. American Psychiatric Association (2022). Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed., Text revision).
  8. Baldessarini, R. J., Vázquez, G. H., & Tondo, L. (2020). Bipolar depression: a major unsolved challenge. International journal of bipolar disorders, 8(1), 1-13.
  9. Jawad, I., Watson, S., Haddad, P. M., Talbot, P. S., & McAllister-Williams, R. H. (2018). Medication nonadherence in bipolar disorder: a narrative review. Therapeutic advances in psychopharmacology, 8(12), 349-363.
  10. Sigitova, E., Fišar, Z., Hroudová, J., Cikánková, T., & Raboch, J. (2017). Biological hypotheses and biomarkers of bipolar disorder. Psychiatry and clinical neurosciences, 71(2), 77-103.
  11.  Drozdz, S. J., Goel, A., McGarr, M. W., Katz, J., Ritvo, P., Mattina, G. F., … & Ladha, K. S. (2022). Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature. Journal of Pain Research, 15, 1691.
  12. Dore, J., Turnipseed, B., Dwyer, S., Turnipseed, A., Andries, J., Ascani, G., … & Wolfson, P. (2019). Ketamine assisted psychotherapy (KAP): patient demographics, clinical data, and outcomes in three large practices administering ketamine with psychotherapy. Journal of psychoactive drugs, 51(2), 189-198.
  13. Kraus, C., Rabl, U., Vanicek, T., Carlberg, L., Popovic, A., Spies, M., … & Kasper, S. (2017). Administration of ketamine for unipolar and bipolar depression. International journal of psychiatry in clinical practice, 21(1), 2-12.
  14.  Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F., Nolan, N. M., Richards, E. M., Brutsche, N. E., … & Zarate, C. A. (2014). Do the dissociative side effects of ketamine mediate its antidepressant effects?. Journal of affective disorders, 159, 56-61.
  15. Majić, T., Schmidt, T. T., & Gallinat, J. (2015). Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences?. Journal of psychopharmacology, 29(3), 241-253.    
  16. Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., … & American Psychiatric Association. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry, 74(4), 399-405.
  17. Gitlin, M. J. (2019). Antidepressants in bipolar depression: an enduring controversy. Focus, 17(3), 278-283.
  18. McIntyre, R. S., Rosenblat, J. D., Nemeroff, C. B., Sanacora, G., Murrough, J. W., Berk, M., … & Stahl, S. (2021). Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation. American Journal of Psychiatry, 178(5), 383-399.
  19. Yatham, L. N., Chakrabarty, T., Bond, D. J., Schaffer, A., Beaulieu, S., Parikh, S. V., … & Post, R. (2021). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations. Bipolar Disorders, 23(8), 767-788.
  20. Spielmans, G. I., Berman, M. I., Linardatos, E., Rosenlicht, N. Z., Perry, A., & Tsai, A. C. (2013). Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS medicine, 10(3), e1001403.

Where to Find
Ketamine TreatmentLocate outpatient ketamine clinics and at-home ketamine service providers in the U.S. that offer care for pain, depression, anxiety, PTSD, OCD, and addiction.