Treatment Resistant DepressionNCT04856124
Intranasal Esketamine to Maintain the Antidepressant Response to IV Racemic Ketamine
An observational study of Treatment Resistant Depression, run by Psych Atlanta at 1 site in United States.
Trial summary
This study aims to assess the efficacy and safety of intranasal esketamine as maintenance antidepressant therapy in patients who have demonstrated clinical improvement with off-label intravenous racemic ketamine for treatment-resistant depression. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Intranasal esketamine
- Type of treatment
- Injection or infusion
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2018to 1 Mar 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Six females and four males with a mean age of 41.1 years. Nine (90%) had one or more psychiatric diagnoses, including generalized anxiety disorder (n = 9), attention deficit hyperactivity disorder (n = 4), post-traumatic stress disorder (n = 3), and panic disorder (n = 1). Six (60%) were unemployed at baseline due to the disabling effects of their depression and five (50%) reported daily suicidal ideation prior to treatment. The duration of the current depressive episode ranged between 5 and 20 years.
Who may be able to join
- Diagnosis of major depression, recurrent, severe without psychotic symptoms according to criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). Must be diagnosed with Treatment resistant depression.
- 18 years old and up Patients had a clinically meaningful response to a course of IV racemic ketamine
Who cannot join
- Active substance abuse, psychosis, significant medical comorbidities, or axis II diagnosis that would interfere with the reliability of outcome measures or response to pharmacotherapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Switching to Intranasal Esketamine Maintains the Antidepressant Response to Intravenous Racemic Ketamine Administration: A Case Series of 10 Patients
This study aims to assess the efficacy and safety of intranasal esketamine as maintenance antidepressant therapy in patients who have demonstrated clinical improvement with off-label intravenous racemic ketamine for treatment-resistant depression.
Read the detailed description
This is a retrospective case series of ten consecutive outpatients with treatment-resistant depression who all had a clinically meaningful response when treated with intravenous racemic ketamine and were then switched to intranasal esketamine for maintenance therapy. Efficacy and adverse effects were assessed at each treatment All patients underwent an extensive consenting process with a detailed discussion about the off-label use of IV racemic ketamine for TRD and known risks of the treatment. Other available approved therapies were offered including alternative medication, TMS, ECT, and VNS. All patients signed an informed consent form prior to treatment and a consent form allowing their data to be used for retrospective research reporting. All patients had baseline lab work and an electrocardiogram to determine medical stability. Patients were encouraged to undergo a series of six ketamine infusions over 14 to 21 days. If a response (>50% improvement) or partial response (25-50% improvement) occurred as determined by a reduction of Montgomery-Asberg Depression Rating Scale (MADRS), Patient Health Questionnaire-9 (PHQ9), and/or a Clinical Global Impressions - Improvement (CGI-I) rating of 3 or more and infusions were well tolerated, patients were offered weekly infusions for four weeks. Patients then had the option of receiving successive maintenance infusions with variable frequency depending on individual patient response and preference. Vital sign and clinical monitoring, dosing, and frequency of IV ketamine treatment were based on the published available data in this area.Treatment with IV ketamine was initiated at subanesthetic doses of 0.5mg/kg with flexible dosing based on response and tolerability up to 1.0mg/kg. Patient's oxygen saturation, blood pressure, and pulse were monitored continuously with pulse oximetry and Caretaker ® finger sensor. Patients that transitioned to IN esketamine received an initial dose of 28mg (n=1) or 56mg (n=9) of IN esketamine and all patients were eventually titrated up to a target dose of 84mg for the remainder of treatments. All patients were monitored as required by the REMS protocol for IN esketamine. Prior to treatment at the beginning of each clinic visit, MADRS and PHQ-9 were completed. CGI ratings were obtained by the treating physician at each treatment. All treatments were administered on-site at the clinic and any adverse effects related to treatment with IV ketamine or IN esketamine were captured through spontaneous reporting and rated as mild, moderate, and severe at the discretion of the treating psychiatrist.
- Conditions
- Treatment Resistant Depression
- Being tested
- Intranasal esketamine
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal esketamineDrug
Also called IV racemic ketamine
Subjects with a clinically meaningful response to IV racemic ketamine were switched to IN esketamine
| Study group | Role | What they receive |
|---|---|---|
| Treatment resistant depressed outpatients | Subjects had a clinically meaningful response to IV racemic ketamine and remained on other psychotropic medications during treatment with both IV ketamine and IN esketamine. Concomitant medication classes included CNS stimulants (n = 7), atypical antipsychotics (n = 6), selective serotonin reuptake inhibitors (n = 5), serotonin/norepinephrine reuptake inhibitors (n = 4), anticonvulsants (n = 3), antipsychotics (n = 3), mood stabilizers (n = 3), benzodiazepines (n = 2), norepinephrine/dopamine reuptake inhibitors (n = 2), alpha 2 antagonists (n=1), and sedative hypnotics (n = 1). Two patients (20%) previously underwent ECT with partial but transient relief from depressive symptoms, two (20%) failed TMS, and no patients reported any period of greater than 50% improvement during their current depressive episode prior to ketamine treatment. Receives: Drug: Intranasal esketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS)
Depression relapse based on MADRS
Measured: 12 months
Secondary outcomes (2)
Patient-Health Questionnaire-9 (PHQ-9)
Depression relapse based on PHQ-9
Measured: 12 months
Clinical Global Impression of Improvement scale- CGI-I
Depression relapse based on CGI-I
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2021
- Study start1 Sep 2018
- Primary completion15 Dec 2020
- Study completion1 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Psych Atlanta
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, michael banov, Psych Atlanta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04856124
- Sponsor's protocol ID
- #1262
- Status last verified
- Apr 2021
- First submitted
- 19 Apr 2021
- Last updated
- 23 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Vekhova KA, Namiot ED, Jonsson J, Schioth HB. Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clin Pharmacol Ther. 2025 Feb;117(2):374-386. doi: 10.1002/cpt.3478. Epub 2024 Oct 20.
PubMed 39428602Banov MD, Landrum RE, Moore MB, Szabo ST. Switching to Intranasal Esketamine Maintains the Antidepressant Response to Intravenous Racemic Ketamine Administration: A Case Series of 10 Patients. J Clin Psychopharmacol. 2021 Sep-Oct 01;41(5):594-599. doi: 10.1097/JCP.0000000000001456.
PubMed 34411009
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switching to Intranasal Esketamine Maintains the Antidepressant Response to Intravenous Racemic Ketamine Administration: A Case Series of 10 Patients
- ClinicalTrials.gov ID
- NCT04856124
- Acronym / sponsor ID
- #1262
- Conditions
- Treatment Resistant Depression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Psych AtlantaUniversity, hospital or other
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 15 Dec 2020 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 23 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to assess the efficacy and safety of intranasal esketamine as maintenance antidepressant therapy in patients who have demonstrated clinical improvement with off-label intravenous racemic ketamine for treatment-resistant depression.
Detailed description
This is a retrospective case series of ten consecutive outpatients with treatment-resistant depression who all had a clinically meaningful response when treated with intravenous racemic ketamine and were then switched to intranasal esketamine for maintenance therapy. Efficacy and adverse effects were assessed at each treatment All patients underwent an extensive consenting process with a detailed discussion about the off-label use of IV racemic ketamine for TRD and known risks of the treatment. Other available approved therapies were offered including alternative medication, TMS, ECT, and VNS. All patients signed an informed consent form prior to treatment and a consent form allowing their data to be used for retrospective research reporting. All patients had baseline lab work and an electrocardiogram to determine medical stability. Patients were encouraged to undergo a series of six ketamine infusions over 14 to 21 days. If a response (>50% improvement) or partial response (25-50% improvement) occurred as determined by a reduction of Montgomery-Asberg Depression Rating Scale (MADRS), Patient Health Questionnaire-9 (PHQ9), and/or a Clinical Global Impressions - Improvement (CGI-I) rating of 3 or more and infusions were well tolerated, patients were offered weekly infusions for four weeks. Patients then had the option of receiving successive maintenance infusions with variable frequency depending on individual patient response and preference. Vital sign and clinical monitoring, dosing, and frequency of IV ketamine treatment were based on the published available data in this area.Treatment with IV ketamine was initiated at subanesthetic doses of 0.5mg/kg with flexible dosing based on response and tolerability up to 1.0mg/kg. Patient's oxygen saturation, blood pressure, and pulse were monitored continuously with pulse oximetry and Caretaker ® finger sensor. Patients that transitioned to IN esketamine received an initial dose of 28mg (n=1) or 56mg (n=9) of IN esketamine and all patients were eventually titrated up to a target dose of 84mg for the remainder of treatments. All patients were monitored as required by the REMS protocol for IN esketamine. Prior to treatment at the beginning of each clinic visit, MADRS and PHQ-9 were completed. CGI ratings were obtained by the treating physician at each treatment. All treatments were administered on-site at the clinic and any adverse effects related to treatment with IV ketamine or IN esketamine were captured through spontaneous reporting and rated as mild, moderate, and severe at the discretion of the treating psychiatrist.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment resistant depressed outpatients | – | Drug: Intranasal esketamineSubjects had a clinically meaningful response to IV racemic ketamine and remained on other psychotropic medications during treatment with both IV ketamine and IN esketamine. Concomitant medication classes included CNS stimulants (n = 7), atypical antipsychotics (n = 6), selective serotonin reuptake inhibitors (n = 5), serotonin/norepinephrine reuptake inhibitors (n = 4), anticonvulsants (n = 3), antipsychotics (n = 3), mood stabilizers (n = 3), benzodiazepines (n = 2), norepinephrine/dopamine reuptake inhibitors (n = 2), alpha 2 antagonists (n=1), and sedative hypnotics (n = 1). Two patients (20%) previously underwent ECT with partial but transient relief from depressive symptoms, two (20%) failed TMS, and no patients reported any period of greater than 50% improvement during their current depressive episode prior to ketamine treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Six females and four males with a mean age of 41.1 years. Nine (90%) had one or more psychiatric diagnoses, including generalized anxiety disorder (n = 9), attention deficit hyperactivity disorder (n = 4), post-traumatic stress disorder (n = 3), and panic disorder (n = 1). Six (60%) were unemployed at baseline due to the disabling effects of their depression and five (50%) reported daily suicidal ideation prior to treatment. The duration of the current depressive episode ranged between 5 and 20 years.
Key inclusion criteria (2 listed)
- Diagnosis of major depression, recurrent, severe without psychotic symptoms according to criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). Must be diagnosed with Treatment resistant depression.
- 18 years old and up Patients had a clinically meaningful response to a course of IV racemic ketamine
Key exclusion criteria (1 listed)
- Active substance abuse, psychosis, significant medical comorbidities, or axis II diagnosis that would interfere with the reliability of outcome measures or response to pharmacotherapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intranasal esketamineAlso: IV racemic ketamineSubjects with a clinically meaningful response to IV racemic ketamine were switched to IN esketamine | Drug | Treatment resistant depressed outpatients |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 12 months
Depression relapse based on MADRS
2 secondary outcomes
Patient-Health Questionnaire-9 (PHQ-9)
Time frame: 12 months
Clinical Global Impression of Improvement scale- CGI-I
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2021.
- Derived from this study: PubMed 39428602Vekhova KA, Namiot ED, Jonsson J, Schioth HB. Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clin Pharmacol Ther. 2025 Feb;117(2):374-386. doi: 10.1002/cpt.3478. Epub 2024 Oct 20.
- Derived from this study: PubMed 34411009Banov MD, Landrum RE, Moore MB, Szabo ST. Switching to Intranasal Esketamine Maintains the Antidepressant Response to Intravenous Racemic Ketamine Administration: A Case Series of 10 Patients. J Clin Psychopharmacol. 2021 Sep-Oct 01;41(5):594-599. doi: 10.1097/JCP.0000000000001456.
Related trials for Treatment Resistant Depression
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Treatment Resistant Depression, run by Psych Atlanta at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04856124, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2021.