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Understanding the Induction and Maintenance Phases of Ketamine Therapy, Boosters, “Off-Label” Use, and More

Ketamine is an FDA-approved anesthetic medication known for rapidly inducing sedation and alleviating pain. It has also proven to be an effective treatment for depression, anxiety disorders, and post-traumatic stress disorder (PTSD). When used for mental health and pain management, ketamine is often administered through a series of intravenous (IV) infusions over the course of several weeks, and its use is considered "off-label." Ketamine infusion clinics typically follow an induction phase with a maintenance phase, where additional infusions (boosters) are spaced at longer intervals.

Another crucial concept in ketamine therapy is the inclusion of psychotherapy, with various methods of combining it alongside ketamine administration. One such approach is ketamine-assisted psychotherapy (KAP). Today, let's take a closer look at the phases of care in ketamine therapy, understanding their unique aspects while exploring the different methods of practice, including ketamine alone versus KAP.

What Does "Off-Label" Ketamine Mean?

Healthcare professionals across the country have been using IV ketamine off-label to treat anxiety and depression, meaning it is prescribed for a use other than its original intended purpose. This practice is not unique to ketamine; in fact, it's estimated that approximately 20% of all drugs prescribed in the United States are used off-label. The percentage varies depending on the drug class and patient population. For instance, off-label use is particularly high in oncology (up to 60%), psychiatry (30-50%), and pediatrics (50-75%). Off-label prescribing reflects common clinical practice, where healthcare professionals rely on their clinical judgment and the latest research to prescribe medications, even if the specific use is not explicitly approved by regulatory agencies like the FDA.

Common Examples of Off-Label Drug Use

Amitriptyline, initially designed for depression, is widely used off-label for neuropathic pain, migraines, fibromyalgia, and interstitial cystitis. Similarly, gabapentin, an antiepileptic drug, is frequently used to treat neuropathic pain, fibromyalgia, restless legs syndrome, and anxiety disorders.

Minoxidil, once intended for hypertension treatment, is now more recognized for its effectiveness in treating androgenetic alopecia (hair loss). Clonidine,, originally an antihypertensive, is also prescribed off-label for ADHD, opioid withdrawal, anxiety, and Tourette syndrome.

Quetiapine, an antipsychotic medication for schizophrenia and bipolar disorder, is often prescribed for insomnia and anxiety disorders. Trazodone, another antidepressant, sees widespread use in treating insomnia and anxiety.

Propranolol, known for hypertension and angina management, has gained prominence for its ability to reduce performance anxiety, essential tremor, and migraines. Prazosin, initially for hypertension, has shown efficacy in relieving PTSD-related nightmares.

Phases of Ketamine Therapy

Induction Phase:

This initial stage of ketamine therapy involves a series of ketamine infusions delivered over a relatively short period to quickly alleviate symptoms and establish a new baseline of improvement. This phase typically consists of six to eight IV infusions administered over three to six weeks, often with 2-3 infusions per week. Dosage is carefully titrated based on individual needs and clinical response. Ketamine is infused intravenously in a controlled clinical setting and under close monitoring by a medical professional to ensure patient safety.

During the induction phase, patients often notice a rapid reduction in symptoms of depression and anxiety, sometimes within hours or days of the first few infusions. For chronic pain, ketamine can quickly decrease pain levels and improve quality of life. Following or immediately after the induction phase, psychotherapy sessions may be integrated to maximize the therapeutic benefits. Ketamine-assisted psychotherapy (KAP) is one approach where ketamine is combined with therapy to enhance introspection and emotional processing.

Maintenance Phase:

After completing the induction phase, clinicians assess the patient's progress using standardized symptom rating scales (e.g., PHQ-9) and clinical evaluation. Based on the response, they recommend the next steps, which often involve a maintenance phase where infusions, referred to as boosters, are spaced out over longer intervals (e.g., monthly, quarterly, or annually) to sustain the therapeutic effects. Booster infusions are structured similarly to those administered during the induction phase in terms of duration and dosage.

The induction phase provides quick symptom relief, allows for the customization of subsequent treatment, and establishes the groundwork for ongoing maintenance therapy. Understanding this phase is crucial for both clinicians and patients to appreciate the structure and potential benefits of ketamine therapy in managing mental health conditions and pain.

A graph that represents the phases of ketamine therapy including the induction phase, maintenance phase, and boosters. The x axis represents time with the y axis represents symptom alleviation. The words "Innerbloom Ketamine Therapy" are centered in the middle of the graph

Figure1: This graph represents the induction and maintenance phases of ketamine therapy. The x-axis represents time, while the y-axis represents the inverse of symptom severity. As shown, symptoms improve following each subsequent infusion during the induction phase until a new baseline is achieved, representing a significant alleviation of symptoms. Over time, symptoms may gradually resurface, as evidenced by a decrease in the y-axis values. If a booster infusion is needed, the goal is to administer it before symptoms return to their original pre-treatment baseline. By utilizing a well-timed booster, the individual can return to the improved baseline achieved after completing the induction series.

Ketamine Alone vs. Ketamine-Assisted Psychotherapy (KAP)

Ketamine Alone:

Ketamine therapy for mental health and pain treatment can be delivered using different methods, each with unique approaches and benefits. One approach is ketamine alone, which involves the administration of ketamine without directly integrating psychotherapy during the treatment sessions. Ketamine can be administered through various routes such as IV or intramuscularly (IM). This method is effective for rapidly alleviating symptoms of depression, anxiety, and PTSD. It also helps reduce suicidal ideation. Ketamine alone is particularly beneficial for patients seeking immediate symptom relief or those who may not be ready for psychotherapy.

Ketamine-Assisted Psychotherapy (KAP):

Ketamine-assisted psychotherapy (KAP) combines ketamine administration with structured psychotherapy sessions to enhance therapeutic outcomes. Before administering ketamine, a preparation session helps establish therapeutic goals and build rapport. During the ketamine session, a facilitator/sitter or therapist may be present with the patient through their experiences, providing support and ensuring the altered state of consciousness remains therapeutic. An integration session follows, where the therapist helps the patient process their experience and integrate insights gained into daily life, addressing underlying psychological issues. KAP enhances the introspective and emotional processing aspects of ketamine therapy, providing holistic healing through deeper emotional processing and increased self-awareness. Insights gained during therapy can lead to sustained mental health improvements.

Which is Better?

The primary difference between ketamine alone and KAP lies in their focus. Ketamine alone emphasizes rapid symptom relief, while KAP combines this with psychotherapy to address deeper psychological issues. The ketamine alone approach does not require structured therapy sessions, whereas KAP involves preparation, ketamine, and integration sessions with a trained therapist. Ultimately, the choice between the two methods depends on individual needs, treatment goals, and clinical judgment, offering either immediate symptom relief or a more holistic approach through emotional processing and insight.

Discussion Summary:

Today, we covered several key topics, including the use of ketamine for treating mental health and pain conditions. While ketamine is used off-label in this context, we clarified that "off-label" does not mean ineffective or unsafe. Instead, it represents a common practice in medical care where practitioners, such as medical doctors, use their best judgment based on the latest research and clinical experience.

We discussed the two phases of ketamine therapy: the induction phase, which involves a series of infusions, and the maintenance phase, which may include booster infusions if necessary. It's essential to note that the need for a booster infusion does not represent treatment failure or warrant discouragement. Instead, it signifies that an effective method of mental health or pain management has been found, which is a positive outcome.

Moreover, individuals undergoing ketamine therapy may be able to taper off or discontinue conventional antidepressant therapy, which often has limited efficacy, high relapse rates, or undesirable side effects.

Lastly, we emphasized the importance of combining psychotherapy with ketamine administration. This combination aims to address the root cause of mental health issues and pain rather than merely providing short-term symptom relief. The potential synergy between psychotherapy and ketamine can help achieve lasting and meaningful improvement in the individual's overall well-being.

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