Ketamine + Esketamine for Depression
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: Benzodiazepines, Opiates, Barbiturates, others
Disqualifiers: Substance use disorder, Bipolar, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The study will consist of a 24-week-long trial examining outcomes in patients with Major Depressive Disorder and suicidal ideation who will receive intravenous (IV) ketamine and intranasal (IN) esketamine, compared to a large sample of matched historical controls. Patients will be recruited from an inpatient psychiatric unit. Eligible patients who provided informed consent will be enrolled in the study that will include a eight IV ketamine treatments, 13 esketamine treatment visits, seven long assessment visits, five short assessment visits, and daily surveys. The study will examine the feasibility, tolerability, and efficacy of repeated IV ketamine followed by esketamine, as well as predictors of treatment response.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently receiving ECT treatment or taking frequent or high doses of certain medications like benzodiazepines, opiates, or barbiturates.
What data supports the effectiveness of the drug Ketamine + Esketamine for depression?
Research shows that both ketamine and esketamine can quickly and effectively reduce depression symptoms, with studies reporting significant improvement in patients, including those with treatment-resistant depression. These drugs have been found to work rapidly, often within hours, and have shown promise in reducing severe suicidal thoughts.
12345Is ketamine and esketamine safe for treating depression?
Research shows that ketamine and esketamine can be safe for treating depression, with some studies reporting only temporary side effects. Long-term safety is still being studied, but they have been approved for use in treatment-resistant depression.
12678What makes the drug Ketamine + Esketamine unique for treating depression?
Ketamine and esketamine offer a rapid antidepressant effect, with subcutaneous administration being a convenient and cost-effective option, especially in developing countries. Esketamine is also available as a nasal spray for treatment-resistant depression, providing an alternative to traditional antidepressants for those who haven't responded to other treatments.
1291011Eligibility Criteria
This trial is for adults aged 18-70 with Major Depressive Disorder and suicidal thoughts, who are inpatients at a psychiatric unit. They must be in good health, not pregnant or breastfeeding, willing to use birth control if applicable, have internet access and a treating psychiatrist. Excluded are those on certain CNS depressants or with recent substance abuse issues.Inclusion Criteria
Ability to read, understand, and provide written and dated informed consent prior to screening
I have a psychiatrist who has been treating me.
Access to a mobile phone or computer with internet connection
+6 more
Exclusion Criteria
Current diagnosis of a moderate to severe substance use disorder, within the last six months prior to screening based on DSM-5 criteria
A status of childbearing potential and is not willing to use birth control during the study
Inability to comply with study safety procedures, including having reliable escorts to and from visits
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive intravenous (IV) ketamine and intranasal (IN) esketamine treatments
24 weeks
8 IV ketamine treatments, 13 esketamine treatment visits, 7 long assessment visits, 5 short assessment visits
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests the effects of IV ketamine followed by IN esketamine over 24 weeks against historical controls for reducing suicide risk in depression patients. It includes multiple treatment sessions, assessments visits, and daily surveys to evaluate feasibility, tolerability and predictors of response.
1Treatment groups
Experimental Treatment
Group I: Ketamine and Esketamine TreatmentExperimental Treatment2 Interventions
All study subjects will receive intravenous (IV) ketamine and intranasal (IN) esketamine treatment.
Esketamine is already approved in United States for the following indications:
🇺🇸 Approved in United States as Spravato for:
- Treatment-resistant depression
- Major depressive disorder with suicidal ideation or behavior
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
American Foundation for Suicide PreventionCollaborator
References
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.
Subcutaneous Ketamine in Depression: A Systematic Review. [2021]Background: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability. Methods: A systematic literature search was carried out, from inception through March, 2021, using PubMed/MEDLINE, EMBASE and Web of Science, with no limits of language. After identifying 159 potentially relevant articles, 12 articles were selected after applying our inclusion/exclusion criteria. These comprised two randomized clinical trials, five case-reports and five retrospective studies. Given the small number of studies found and their heterogeneous nature, a meta-analysis was not considered appropriate. Here we provide a synthesis of these data including participant characteristics, dose range, efficacy, safety/ tolerability. Risk of bias was accessed using the Cochrane risk of bias tool. Results: SC Ketamine was administered to unipolar and bipolar patients a single or multiple doses, weekly or twice-weekly, a dose-titration approach was made in major studies, dose ranged from 0.1 to 0.5 mg/Kg of racemic ketamine and 0.5-1 mg/Kg of esketamine. Across all studies, SC ketamine showed a rapid and robust antidepressant effect, with response/ remission rates from 50 to 100% following both single or multiple doses, with transitory side effects. Conclusion: SC racemic ketamine and esketamine in depression is a promising strategy showing beneficial efficacy and tolerability. Future studies exploring the SC route, its cost-effectiveness, and a direct comparison with IV and intranasal (IN) protocols are warranted. Systematic Review Registration: CRD42019137434.
Intravenous ketamine therapy in a patient with a treatment-resistant major depression. [2022]Recently, reports from North America have indicated that the intravenous infusion of ketamine hydrochloride (an N-methyl-d-aspartate receptor antagonist) results in a sudden and robust improvement of depression symptoms.
Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. [2018]Ketamine in a subanaesthetic dose has been shown to produce rapid antidepressant effects. Here, we describe a long-term follow-up case of a Korean patient with severe major depression who received repeated ketamine intravenous therapy (KIT).
Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. [2022]To confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group.
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.
Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis. [2023]Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. We aimed to review the efficacy and safety of racemic and esketamine for depression.
Long-term safety of ketamine and esketamine in treatment of depression. [2022]Ketamine can produce rapid-acting antidepressant effects. Esketamine (Spravato), the S-enantiomer of racemic ketamine, was approved by the FDA for treatment-resistant depression in 2019. Here we review what is known about the long-term safety of both racemic ketamine and esketamine as therapies for psychiatric disorders.
Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression. [2022]Esketamine nasal spray is approved for treatment-resistant depression.
Repeated subcutaneous esketamine administration for depressive symptoms and pain relief in a terminally ill cancer patient: A case report. [2021]Depressive disorders are common among cancer patients. Ketamine can quickly relieve depression, and its subcutaneous administration appears to be as effective as and probably safer than its standard intravenous administration. Herein, we report a case verifying the antidepressant effect of a subcutaneous esketamine formulation.
Esketamine for treatment-resistant depression. [2021]Generic name: Esketamine hydrochloride Brand name: Spravato Formulation: 28mg in 0.2ml nasal spray solution Market Authorisation holder: Janssen-Cilag International NV Indication: Treatment resistant major depressive disorder in adults who have failed to respond to at least two different antidepressants during the current moderate to severe episode. To be used in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI). Dose: The starting dose is 56 mg for adults aged <65 years and 28 mg for adults aged ≥65 years 1 Subsequent doses (56 mg or 84 mg for those <65 years; 28 mg, 56 mg or 84 mg for those ≥65 years) are given twice a week for 4 weeks, followed by once a week for 4 weeks, and then once a week or once every 2 weeks from week 9. Treatment is recommended for at least 6 months after symptoms improve. Cost: £163 for 28 mg (one device) Classification: Prescription only medicine (POM) subject to additional monitoring (▼). Controlled drug schedule 2.