Ketamine-Assisted Psychotherapy for Depression (KAP Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Icahn School of Medicine at Mount Sinai
No Placebo Group
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This trial compares two treatments for adults with severe depression. One treatment uses ketamine combined with therapy, and the other uses only ketamine. Ketamine helps improve mood by changing brain chemistry, and therapy might make these improvements last longer. Ketamine, originally a dissociative anesthetic, has been increasingly used for treatment-resistant depression due to its rapid antidepressant effects.
What safety data exists for ketamine-assisted psychotherapy for depression?Existing safety data for ketamine-assisted psychotherapy for depression includes evidence from systematic reviews and meta-analyses, which summarize the efficacy and safety of ketamine and esketamine. Ketamine has been used safely for decades, making it suitable for office and supervised at-home use. However, there are emerging adverse events, such as apnea during slow sub-anaesthetic infusion, which are generally transient but require careful monitoring. The Ketamine Side Effect Tool (KSET) has been developed to comprehensively measure safety in psychiatric use. Overall, while ketamine is effective, safety monitoring and reporting of adverse events are crucial.12346
Do I have to stop taking my current medications for the trial?No, you can continue taking your current medications for depression as long as you stay on a stable dose.
Is Ketamine-Assisted Psychotherapy a promising treatment for depression?Yes, Ketamine-Assisted Psychotherapy is a promising treatment for depression. It combines the drug ketamine with therapy to help reduce depression and anxiety, especially in people who haven't responded to other treatments. It has shown positive results in both adults and adolescents, helping improve symptoms and overall well-being.258910
What data supports the idea that Ketamine-Assisted Psychotherapy for Depression is an effective treatment?The available research shows that Ketamine-Assisted Psychotherapy (KAP) is effective in reducing depression and anxiety, especially in older patients and those with severe symptoms. In a study of 235 patients, KAP was found to be beneficial in a private practice setting. Additionally, in adolescents with multiple psychiatric diagnoses, KAP led to improvements in symptoms and functioning. This suggests that KAP can be a promising treatment for depression, offering rapid relief and being well-tolerated by patients.257910
Eligibility Criteria
This trial is for adults with major depressive disorder (MDD). Participants will be randomly assigned to receive either ketamine-assisted psychotherapy or just ketamine without psychotherapy over four weeks, followed by an 8-week observation period.Inclusion Criteria
I am between 18 and 90 years old.
I am currently experiencing moderate to severe depression.
I have been diagnosed with major depressive disorder.
Exclusion Criteria
I have experienced psychotic symptoms during my current depressive episode or have a history of psychotic disorder.
I do not have any unstable illnesses affecting my organs or immune system.
I do not have any major health issues found in blood tests, physical exams, or heart tests.
I have not responded to ketamine or esketamine treatments before.
I am currently receiving ECT, TMS, or VNS for my depression.
My BMI is over 35.
My cognitive test score is below 23.
Treatment Details
The study compares two treatments for depression: one combines ketamine with psychotherapy (KAP), and the other uses only ketamine (KET). The effectiveness of each treatment will be measured through changes in depression severity and wellness.
2Treatment groups
Experimental Treatment
Active Control
Group I: Ketamine Assisted Psychotherapy (KAP)Experimental Treatment2 Interventions
KAP sessions will occur once a week for a total of 4 weeks with the potential for a second session the first week for dose-finding purposes. Participants will have a ketamine exposure of at least 0.3 mg/kg and a maximum of 1.0mg/kg, at each treatment session, personalizing dose to patient experience. Each of the treatment sessions will last 120-180 min and will be conducted by a single therapist who has completed the KAP training as specified in the standard operating procedures.
Group II: Ketamine (KET)Active Control1 Intervention
Standard medicalized ketamine administration consisting of twice weekly treatment for 3 weeks, followed by a 4th week with a single ketamine infusion serving as a down-titration period before discontinuation. Participants will have a ketamine exposure of at least 0.3 mg/kg administered via intravenous infusion at each treatment session. Patients may be up-titrated over the course of subsequent treatment sessions, as indicated clinically up to 1.0 mg/kg25. No formal psychotherapy will be provided in the KET arm, though study participants will have matched basic psychoeducation related to depression and treatment with ketamine prior to the first dosing session, during the ketamine treatment period, and post-treatment, in order to match the KAP arm. All individuals will be followed over an eight week follow up period and undergo clinical study assessments.
Ketamine-Assisted Psychotherapy is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Esketamine for:
- Treatment-resistant depression
- Major depressive disorder with acute suicidal ideation or behavior
🇪🇺 Approved in European Union as Ketamine for:
- Anesthesia
- Not specifically approved for psychiatric indications but used off-label
🇨🇦 Approved in Canada as Esketamine for:
- Treatment-resistant depression
Find a clinic near you
Research locations nearbySelect from list below to view details:
Icahn School of Medicine at Mount SinaiNew York, NY
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Who is running the clinical trial?
Icahn School of Medicine at Mount SinaiLead Sponsor
References
Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. [2013]Narrative review of the literature on the efficacy and safety of subanaesthetic doses of ketamine for the treatment of depression.
Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy. [2020]Currently, ketamine is the only legal psychedelic medicine available to mental health providers for the treatment of emotional suffering. Over the past several years, ketamine has come into psychiatric use as an intervention for treatment resistant depression (TRD), administered intravenously without a psychotherapeutic component. In these settings, ketamine's psychedelic effects are viewed as undesirable "side effects." In contrast, we believe ketamine can benefit patients with a wide variety of diagnoses when administered with psychotherapy and using its psychedelic properties without need for intravenous (IV) access. Its proven safety over decades of use makes it ideal for office and supervised at-home use. The unique experience that ketamine facilitates with its biological, experiential, and psychological impacts has been tailored to optimize office-based treatment evolving into a method that we call Ketamine Assisted Psychotherapy (KAP). This article is the first to explore KAP within an analytical framework examining three distinct practices that use similar methods. Here, we present demographic and outcome data from 235 patients. Our findings suggest that KAP is an effective method for decreasing depression and anxiety in a private practice setting, especially for older patients and those with severe symptom burden.
Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. [2021]Ketamine's pharmacological profile makes it an interesting and useful drug to challenge treatment-resistant-depression (TRD). Emerging adverse events associated with single-slow-sub-anaesthetic doses for the treatment of depression are common, although generally transient and self-limited. Nevertheless, data on the safety of this practice are scarce. Thus, it seems timely before ketamine is used for clinical treatment of depression to recommend careful monitoring and reporting of all potential adverse events related to ketamine administration. Here, we describe a case of apnea during slow sub-anaesthetic infusion of intravenous ketamine for the treatment of resistant depression. As far as we are concerned, this is an uncommon, previously unreported, and potentially severe adverse event that clinicians should be aware of, and specific management measures should be implemented.
Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. [2022]To summarize the evidence of efficacy and safety of the use of ketamine and esketamine for depression.
Toward Synergies of Ketamine and Psychotherapy. [2022]Ketamine is a dissociative drug that has been used medically since the 1970s primarily as an anesthetic agent but also for various psychiatric applications. Anecdotal reports and clinical research suggest substantial potential for ketamine as a treatment in conjunction with psychological interventions. Here, we review historical and modern approaches to the use of ketamine with psychotherapy, discuss the clinical relevance of ketamine's acute psychoactive effects, propose a unique model for using esketamine (one isomeric form of ketamine) with Acceptance and Commitment Therapy (ACT), and suggest considerations for moving medication-assisted psychotherapy forward as a field.
The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]On a background of the rapidly expanding clinical use of ketamine and esketamine for treatment of depression and other conditions, we examined safety monitoring, seeking to identify knowledge gaps relevant to clinical practice.
A case series of group-based ketamine-assisted psychotherapy for patients in residential treatment for eating disorders with comorbid depression and anxiety disorders. [2022]Depression and anxiety outcome measures, safety/tolerability, patient satisfaction, and ease of implementation of group-based ketamine-assisted psychotherapy (G-KAP) delivered to patients in intensive residential eating disorder (ED) treatment were assessed.
Active mechanisms of ketamine-assisted psychotherapy: A systematic review. [2022]Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD).
Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses. [2023]Ketamine-assisted psychotherapy is a promising new treatment for a variety of mental disorders of adolescence. There is currently an adolescent mental health crisis, with a high prevalence of disorders, diagnostic complexity, and many adolescents failing to respond to conventional treatments. While there is strong evidence for the use of ketamine in adults for a variety of treatment-refractory mental illnesses, research in adolescents is in its early stages. Ketamine-assisted psychotherapy (KAP) has been described in adults with promising results and here we present the first published cases of the use of KAP in adolescents. The four cases include adolescents aged 14-19 at the initiation of treatment, each with a variety of comorbid diagnoses including treatment-resistant depression, bipolar disorder, eating disorders, anxiety, panic, and trauma-related symptoms. They each initially received sublingual ketamine, followed by sessions with intramuscular ketamine. Their courses varied, but each had symptomatic and functional improvements, and the treatment was well-tolerated. Subjective patient reports are included. Rapid resolution of symptomatology and suffering often occurs within months as the result of the application of KAP to adolescent psychiatric care but is not inevitable. Family involvement in the treatment process appears to be essential to success. The development of this modality may have a singularly positive impact that will expand the psychiatric toolbox and its healing potency.
Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review. [2023]Ketamine is an effective short-term treatment for a range of psychiatric disorders. A key question is whether the addition of psychotherapy to ketamine treatment improves outcomes or delays relapse.