Understanding the Mechanism of Ketamine Infusion Therapy

Theodora Blanchfield, an Associate Marriage and Family Therapist and dedicated mental health author, leverages her clinical psychology expertise from Antioch University to support others. She serves on the board of Still I Run, a nonprofit focused on mental health awareness among runners. Her work has been featured in Women’s Health, Bustle, Healthline, and quoted by prominent outlets like the New York Times, Shape, and Marie Claire.

Ketamine infusion therapy represents a groundbreaking treatment option for select mental health disorders, notably those unresponsive to traditional therapies such as treatment-resistant depression and anxiety.

Initially developed as an anesthetic, ketamine’s antidepressant properties were identified as early as 1975. Although early anecdotal evidence from recreational users hinted at its benefits, its illegal status delayed formal recognition.

Scientific investigations into ketamine's therapeutic potential began in the late 1990s, culminating in a 2000 study that highlighted promising outcomes for ketamine infusion therapy.

In 2019, the FDA approved Spravato (esketamine) for individuals with depression unresponsive to at least two antidepressant medications—a condition more prevalent than commonly assumed, affecting over half of patients on initial antidepressants.

Administration Methods

Among various delivery methods, ketamine infusions are noted for optimal absorption and efficacy, though treatment choice may depend on clinical setting preferences and cost considerations.

• Intravenous infusions: Administered in clinical environments over approximately 40 minutes.
• Intramuscular injections: Delivered into large muscles like the thigh or arm, with effects lasting about 40 minutes, typically in medical settings.
• Lozenges (troches): Oral administration suitable for home or clinic use, often prescribed as primary or maintenance therapy between other forms.
• Nasal sprays: Includes FDA-approved Spravato, administered under medical supervision with post-treatment monitoring, and compounded nasal sprays customized by pharmacies per physician guidance.

Primary Uses of Ketamine Infusion Therapy

Ketamine infusion therapy is primarily utilized for treatment-resistant depression, diagnosed when patients fail to respond adequately to multiple antidepressant treatments.

It also shows efficacy in addressing acute suicidal crises and persistent suicidal thoughts.

Additional mental health conditions benefiting from ketamine treatment include:

• Post-traumatic stress disorder (PTSD)
• Chronic pain syndromes
• Anxiety disorders
• Bipolar disorder
• Obsessive-compulsive disorder (OCD)
• Suicidal ideation

If experiencing suicidal thoughts, immediate support is available via the National Suicide Prevention Lifeline at 988. In emergencies, call 911. Additional mental health resources can be found in our National Helpline Database.

Advantages of Ketamine Infusion Therapy

Unlike traditional antidepressants that may take weeks to show effects, ketamine infusion can rapidly alleviate symptoms. For example, a study revealed that 88% of emergency room patients experienced resolution of suicidal thoughts within 90 minutes post-infusion.

Ketamine promotes glutamate release in the brain, a neurotransmitter linked to mood regulation. This process fosters the creation and repair of neural connections, enhancing brain plasticity.

These newly formed neural pathways facilitate positive cognitive and behavioral changes, contrasting with conventional antidepressants which only act while present in the system.

Improvements may be observed in depressive mood, suicidal ideation, and feelings of helplessness or worthlessness.

Effectiveness Overview

Ketamine infusion therapy is recognized for its transformative potential, with studies reporting remission rates of depressive symptoms in approximately 85% of patients, defined as a 50% or greater symptom reduction.

While not a definitive cure, symptom relapse typically occurs around 19 days post-treatment, though some patients maintain remission for over three months.

Considerations Before Treatment

Prior to initiating ketamine infusion therapy, it is important to understand potential side effects and eligibility criteria.

Possible Side Effects

Administered at sub-anesthetic doses, ketamine infusions may cause transient side effects that usually resolve within hours:

• Nausea
• Dizziness
• Double vision
• Drowsiness
• Confusion

Given ketamine’s dissociative properties, some patients might experience sensations such as out-of-body feelings or detachment from their body, which are temporary and part of the therapeutic process.

Who Should Avoid Ketamine Infusions

Ketamine therapy may be contraindicated for individuals with conditions like schizophrenia, uncontrolled hypertension, or acute alcohol intoxication.

Maximizing Your Treatment Experience

• Reduce stress prior to sessions by avoiding distressing content such as news.
• Create a calming atmosphere with instrumental music to enhance relaxation.
• Engage in meditation before infusions to ease mental activity.
• Coordinate with your therapist to integrate ketamine therapy into your overall mental health plan.

Initiating Ketamine Infusion Therapy

Finding a Qualified Provider

Locating a reputable ketamine therapy provider can be challenging. The American Society of Ketamine Physicians, Psychotherapists & Practitioners (ASKP) offers a directory of vetted professionals adhering to stringent ethical standards.

What to Expect During Your First Visit

Your initial appointment typically involves a comprehensive evaluation of your mental health history, previous treatments, and current medications. This is also an opportunity to discuss any questions and assess your suitability for therapy.

Standard treatment protocols usually consist of six infusions over two to three weeks, followed by ongoing assessments. Maintenance infusions may be scheduled monthly or as needed.

The infusion session lasts approximately 40 minutes, during which vital signs are monitored. Patients may be offered eye masks and headphones to facilitate comfort and relaxation. Effects such as mild dissociation may begin within minutes but are temporary.

Post-infusion, patients remain under observation for 20 to 30 minutes and should arrange transportation home, as driving is not advised.

Rest and reflection post-treatment support the brain’s adaptive processes and the development of positive thought patterns.

Explore further resources on therapy and getting started with ketamine treatments.

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2. Domino EF, Warner DS. Taming the ketamine tiger. Anesthesiology. 2010;113(3):678-684. doi:10.1097/ALN.0b013e3181ed09a2
3. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biological Psychiatry. 2000;47(4):351-354. doi:10.1016/s0006-3223(99)00230-9
4. NIMH questions and answers about the NIMH sequenced treatment alternatives to relieve depression (STAR*D) study — all medication levels.
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7. Can AT, Hermens DF, Dutton M, et al. Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study. Transl Psychiatry. 2021;11:101. doi:10.1038/s41398-021-01230-z
8. Abdallah CG, De Feyter HM, Averill LA, et al. The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology. 2018;43(10):2154-2160. doi:10.1038/s41386-018-0136-3
9. Mathew SJ, Shah A, Lapidus K, et al. Ketamine for treatment-resistant unipolar depression. CNS Drugs. 2012;26(3):189-204. doi:10.2165/11599770-000000000-00000

By Theodora Blanchfield, AMFT
Theodora Blanchfield is an Associate Marriage and Family Therapist and mental health writer who draws on her clinical psychology background to assist others. She holds a master's degree from Antioch University and serves on the board of Still I Run, a nonprofit promoting mental health awareness among runners. Her work appears in Women’s Health, Bustle, Healthline, and she has been quoted in the New York Times, Shape, and Marie Claire.

Updated by Hannah Owens, LMSW

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