Ketamine for Bipolar Disorder Treatment

Key Takeaways

• Ketamine can quickly improve mood in people with bipolar depression, often within hours.
• Ketamine works by affecting the glutamate system in the brain, which helps with learning and memory.
• Ketamine treatments can be expensive and are not always covered by insurance.

You may have heard about ketamine treatment for depression, but did you know ketamine can also be used to treat bipolar disorder? Specifically, it is used to treat the depression “pole” of bipolar.

Ketamine is being lauded as a treatment for depression as it can improve mood quickly—often within hours. Because bipolar disorder has such a high rate of treatment resistance and suicidality, this can be significant, as conventional treatments for mood disorders often take some time to work.

How Does Ketamine for Bipolar Treatment Work?

Ketamine exists in two different forms chemically—r-ketamine and s-ketamine. They are enantiomers, meaning they have the same chemical formula but are mirror images of one another.

A mix of R-ketamine and S-ketamine is generally used for IV infusions, and generally show more robust effects than s-ketamine (typically used in Spravato nose spray).

Ketamine is thought to be so effective because it works on so many different systems in the brain. One of the biggest systems it works on is the glutamate system. Glutamate is an excitatory neurotransmitter that helps neurons communicate. In fact, it is present in upwards of 90% of all synapses in the brain. 

When someone has been dealing with chronic stress or chronic depression the glutamate system can be dysregulated.

Ketamine is an N-methyl-D-asparate (NMDA) antagonist, which means that it influences the activity of glutamate in the brain. Learning, memory and neuroplasticity processes all depend on the activities of the NMDA receptors.

First, ketamine induces changes in brain chemistry, which can improve symptoms in hours (hence the rapid decrease in suicidality). It then stimulates the growth of synapses, which help neurons in the brain connect with each other.

Decreased neuronal synapses are often observed in depression, but ketamine increases the formation of new synapses in the brain, which help builds neural plasticity.

How Effective Is Ketamine for Bipolar Disorder Treatment?

One of the most powerful arguments for using ketamine for bipolar treatment is its rapid response. People with bipolar disorder face a rate of 20 times more than the general population for death by suicide.

Additionally, upwards of 25% of those with bipolar disorder are treatment-resistant, meaning at least two or more mood agents have failed.

Because of these statistics, finding an effective treatment that works rapidly is key. In one study, more than 75% of patients responded to ketamine within 40 minutes, with decreased mood symptoms and suicidal ideation, while 0% responded to treatment as usual in that time period.

Benefits of Ketamine for Bipolar Disorder

Some researchers describe three different ways of working with ketamine to treat bipolar depression.

• Biochemical Paradigm: This is the use of ketamine infusions or other forms of the medication for mood disorders as a stand-alone treatment without concurrent psychotherapy or other behavioral strategies or interventions.
• Psychotherapeutic Paradigm: The psychotherapeutic paradigm involves using ketamine as a catalyst or lubricant for the psychotherapy process, helping facilitate the emotional expression and integration of meaningful emotional content during the administration. This is similar to the ways in which MDMA is being studied to be used in the psychotherapy of PTSD.
• Psychedelic Paradigm: The final school of thought approaches ketamine the way others approach more “traditional” psychedelics such as psilocybin or LSD. Whereas biochemical and psychotherapeutic applications of ketamine treatment deliberately keep the dosages sub-dissociative, the psychedelic model purposely uses the medicine to create an intentionally altered state of consciousness. There is some research that psychedelic experiences such as awe may correlate with greater improvement in mood symptoms in some cases.

Things to Consider

Although ketamine is generally safe and well-tolerated in medical settings, it is still a powerful treatment that can be expensive and have some side effects you will want to know about.

Cost

Ketamine treatment can be very expensive, with infusions running upwards of several hundred dollars and not always covered by insurance. Spravato (esketamine) is the only form of ketamine that is FDA-approved for depression, which may make it eligible for insurance coverage, but depending on insurance, it still may be costly.

Time

Because ketamine, in most of its formats, will cause some dissociative effects, and/or dizziness/fogginess, you will be recommended not to drive anywhere from six to 24 hours, so you may need to depend on others to drive you. It is generally administered two to three times a week for a few weeks.

Additionally, you will want to factor in time to prepare yourself mentally for treatment, as well as time after for recovery—so, in addition to the financial commitment, it is also a time commitment.

Mania

Although there is limited evidence of ketamine causing a switch from depression to mania, the potential for this danger does exist.

Substance Use 

Although ketamine is a substance with addictive potential, when used therapeutically, the risks appear to be relatively low (but not zero). In fact, ketamine treatment has even been found to help some dealing with certain substance use issues.

Physical Side Effects

Ketamine was originally developed as an anesthetic (though it is given at  significantly higher doses for anesthesia than for bipolar treatment), many of the side effects are similar to those you might deal with if you were under anesthesia, though they are all temporary and should subside within a few hours.

Temporary side effects may include nausea, mild sedation and/or dizziness. Also, it may interact with certain other medications.

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

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By Theodora Blanchfield, AMFT

Theodora Blanchfield is an Associate Marriage and Family Therapist and mental health writer using her experiences to help others. She holds a master’s degree in clinical psychology from Antioch University and is a board member of Still I Run, a non-profit for runners raising mental health awareness. Theodora has been published on sites including Women’s Health, Bustle, Healthline, and more and quoted in sites including the New York Times, Shape, and Marie Claire.

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