Ketamine has been shown to rapidly alleviate depressive symptoms in patients with treatment-resistant major depressive disorder (TRD). It has also demonstrated effectiveness in treating other mental health conditions, such as anxiety, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD). Additionally, ketamine may be used for individuals experiencing substance abuse and physical pain.

How Ketamine Works

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It is believed that ketamine's primary mechanism of action involves glutamate modulation, leading to increased synaptic excitability. Ketamine is thought to increase neuroplasticity and synaptogenesis. Animal studies suggest ketamine can elevate brain-derived neurotrophic factor (BDNF) levels, which can reduce the effects of acute and chronic stress.

What a Ketamine Session Looks Like

A typical ketamine session varies depending on the setting and method of administration. Patients are usually in a comfortable, supervised environment, either in a clinical setting or at home under medical guidance. The session begins with a period of relaxation before the ketamine is administered. Patients may experience altered states of consciousness, vivid imagery, and emotional processing during the session. The effects typically last between 45 minutes to a few hours, and patients are often encouraged to reflect on their experiences with the guidance of a therapist or healthcare provider.

Methods of Ketamine Administration

Ketamine can be ingested in several ways, each with its own unique effects and duration:

• Intravenous (IV) Infusion: The most common clinical method, providing precise dosing and rapid effects, typically within minutes.
• Nasal Spray: A non-invasive option available through prescription, with effects that begin within 15-30 minutes.
• Troches (Lozenges): Dissolvable tablets placed under the tongue, often used in at-home therapy protocols, with a slower onset of effects compared to IV or nasal administration.

Ketamine-Assisted Psychotherapy (KAP)

Ketamine-assisted psychotherapy (KAP) combines ketamine use with psychotherapy sessions to treat mental disorders. The neuroplasticity-promoting effects of ketamine are thought to strengthen the cognitive restructuring that occurs during psychotherapy, leading to lasting behavioral changes. KAP may involve preparation sessions, support during ketamine administration, and integration sessions following ketamine treatment. Psychotherapeutic modalities, such as cognitive behavioral therapy, motivational enhancement therapy, and functional analytic psychotherapy, can be paired with ketamine.

Ketamine for Treatment-Resistant Depression (TRD)

Ketamine has been studied for its antidepressant effects, particularly in treatment-resistant depression (TRD). A single dose of ketamine can have rapid antidepressant effects that last up to a week. Ketamine has also been shown to reduce suicidality in some patients with suicidal ideation.

Ketamine in Couple Therapy

Ketamine may improve couple therapy by addressing cognitive, emotional, and behavioral aspects of the therapy. Ketamine may decrease emotional inhibition and rigidity, thus improving empathy and connection. Ketamine may reduce negative behaviors, such as avoidance and reactivity, and improve the willingness to attempt new positive behaviors. A proposed framework for ketamine-assisted couple therapy involves KAP preparation, dosing, and integration within a dyadic intervention framework.

The Future of Ketamine Therapy

Further research is needed to understand the effects and mechanisms of action of ketamine. Studies should focus on integrating ketamine with various forms of therapy. Research should also explore the intraindividual mechanisms of ketamine effects, especially in the context of ketamine-assisted couple therapy.

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