Major Depressive DisorderPhase 4NCT05450432
Long-Term Maintenance With Ketamine and Esketamine for Reduction of Suicide in High-Risk Patients With Depression
A Phase 4 study testing Ketamine and Esketamine in people with Major Depressive Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Ketamine and Esketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2022to 1 Jun 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inpatient at a psychiatric unit (or MGH medical unit, awaiting transfer to psychiatry).
- Male and female, 18-70 years of age, inclusive, at screening.
- Diagnosis of MDD, single or recurrent, and currently experiencing a major depressive episode (MDE) at least eight weeks in duration, prior to screening, according to the criteria defined in the Diagnosis and Statistical manual of Mental Disorders, Fifth Edition (DSM-5). The diagnosis of MDD will be made by a site psychiatrist and supported by the Mini-International Neuropsychiatric Interview (MINI).
- Suicidal ideation determined by a minimum score of 1 on item 12 of the QIDS-C assessment and based on admission to the inpatient unit for suicidal thoughts or behaviors.
- In good general health, as ascertained by medical history. If needed to verify health status, the investigator may order/conduct physical examination (PE) (including measurement of supine and standing vital signs), clinical laboratory evaluations, or ECG.
- A status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:
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- 1. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her last menses at least one year prior to screening); or 2. Childbearing potential, and meets the following criteria:
- Childbearing potential, including women using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent.
- Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test prior to receiving study treatment.
- Willing and able to continuously use a method of birth control during the course of the study (implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence). The form of birth control will be documented at screening.
- 7. Access to a mobile phone or computer with internet connection. 8. Ability to read, understand and provide written and dated informed consent prior to screening.
- 9. Must have a provider to manage psychiatric medication, such as a psychiatrist, nurse practitioner, primary care physician, etc., either prior to admission or at discharge from the inpatient unit.
Who cannot join
- Any history of previous treatment with IV ketamine.
- Pregnant or breastfeeding.
- Subject of childbearing potential who is not willing to use birth control during the study.
- Unstable medical illness, i.e., severe liver or kidney disease, uncontrolled hypertension, uncontrolled hyperthyroidism
- Current diagnosis of a moderate to severe substance use disorder (excluding mild or moderate alcohol or cannabis use disorder which will be permitted), within the last six months prior to screening based on DSM-5 criteria.
- History of bipolar disorder, or any psychotic symptoms in the current or previous depressive episodes.
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- An Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant to their MDD at any time within six months prior to screening (i.e., eating disorder, OCD, PTSD).
- Currently receiving ECT treatment.
- Currently receiving frequent or high dose benzodiazepines, opiates, barbiturates, or other CNS depressant medications, based on an increased risk of sedation in combination with ketamine.
- Has dementia, delirium, amnestic, or any other primary cognitive disorder.
- Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results according to a licensed physician on the study staff.
- Inability to consent to or comply with the study procedures.
- Other medical issues:
- Hypertension, (SBP ≥160 mmHg or DBP ≥100 mHg) at Screening - untreated
- Recent myocardial infarction (within one year)
- Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention which, according to the screening done by a licensed physician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years
- Thyroid stimulating hormone (TSH) outside of the normal limits and clinically significant as determined by the Investigator.
- Any other clinically significant abnormal laboratory result (determined as such by the Investigator and/or medical monitor) at the time of the screening.
- Patients with diabetes mellitus fulfilling any of the following criteria:
- 1. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.5% at screening.
- 2. Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus- related illness in the past 12 weeks.
- Patients with a history of narrow angle glaucoma - untreated 14. Inability to comply with ketamine clinic safety procedures, including having reliable escorts to and from visits.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Catherine Schuessler, BS, 617-643-7690, mghketamindstudy@partners.org
Catherine Schuessler, BS, mghketamindstudy@partners.org
About this study
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.
- Conditions
- Major Depressive Disorder
- Being tested
- Ketamine, Esketamine
- Keywords
- depression, suicidal ideation
- Medical subject headings
- Depressive Disorder, Major, Depression, Suicidal Ideation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Study participants will start treatment including two ketamine infusion visits per week during the acute phase, for up to eight ketamine infusion visits. Participants will then be transitioned to maintenance with intranasal esketamine.
EsketamineDrug
After one month from the eighth ketamine infusion visit, participants will initiate weekly esketamine for 12 weeks, for a total of 13 esketamine treatments. The esketamine visits will happen as per standard of care at the clinic and as instructed by the SPRAVATO Risk Evaluation and Mitigation Strategy.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine and Esketamine Treatment | Other | All study subjects will receive intravenous (IV) ketamine and intranasal (IN) esketamine treatment. Receives: Drug: Ketamine; Drug: Esketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility - Retention
For examining the feasibility of treatment with ketamine and esketamine, descriptive analyses will be conducted to assess participants' retention across study visits.
Measured: 24 weeks
Feasibility - Drop-out Rates
For examining the feasibility of treatment with ketamine and esketamine, descriptive analyses will be conducted to assess participants' drop-out rates across participation in the study.
Measured: 24 weeks
Tolerability - Cognitive Function and Side Effects
In regard to tolerability, the investigators will closely monitor cognitive functions and side effects during the administration of ketamine and esketamine.
Measured: Weeks 0, 1, 2, 3, 4, 8, and 12-24
Tolerability - Dosage of Treatment
In regard to tolerability, the investigators will record the Necessary Clinical Adjustments (NCAs) for dosage of ketamine and esketamine treatments.
Measured: Change between weeks 0, 4, 6, 8, 10, 12, 14, 16, 20, 22, and 24
Tolerability - Frequency of Treatment
In regard to tolerability, the investigators will record the Necessary Clinical Adjustments (NCAs) for the frequency of ketamine and esketamine administration.
Measured: Change between weeks 0, 4, 6, 8, 10, 12, 14, 16, 20, 22, and 24
Secondary outcomes (6)
Efficacy - Treatment Response
Descriptive analyses will be performed for percentage of responders (defined as 35% improvement on the QIDS-16) at the end of the IV ketamine acute phase, after the eighth ketamine infusion, and across the esketamine maintenance phase.
Measured: Weeks 4, 8, and 12-24
Efficacy - Trajectory of Suicidal Ideation
The change in participants' suicidal ideation will be examined over time and compared to historical controls.
Measured: 24 weeks
Efficacy - Trajectory of Depression
The change in participants' depression will be examined over time and compared to historical controls.
Measured: 24 weeks
Efficacy - Hospital Readmission Rates
The change in participants' hospital readmission rates will be examined over time and compared to historical controls.
Measured: 24 weeks
Efficacy - Prevalence of Suicidal Behavior
The occurrence of suicidal behavior (gestures, attempts, and completed suicide) among participants will be examined over time and compared to historical controls.
Measured: 24 weeks
Efficacy - Healthcare Utilization
The change in participants' healthcare utilization rates will be examined over time and compared to historical controls.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2022
- Study start13 Oct 2022
- Primary completion1 Jun 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A total of 100 participants will be enrolled in the study to receive intravenous ketamine and intranasal esketamine. Participants will be compared against matched historical control subjects identified through electronic medical records.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- American Foundation for Suicide Prevention
- Responsible party
- Principal investigator, Cristina Cusin, MD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05450432
- Sponsor's protocol ID
- 2022P000972
- Status last verified
- Dec 2025
- First submitted
- 16 Jun 2022
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The investigators do not plan to share IPD.
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-Term Maintenance With Ketamine and Esketamine for Reduction of Suicide in High-Risk Patients With Depression
- ClinicalTrials.gov ID
- NCT05450432
- Acronym / sponsor ID
- 2022P000972
- Conditions
- Major Depressive Disorder
- Keywords
- depression, suicidal ideation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- American Foundation for Suicide Prevention
- Study start
- 13 Oct 2022 (actual)
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 8 Jul 2022 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A total of 100 participants will be enrolled in the study to receive intravenous ketamine and intranasal esketamine. Participants will be compared against matched historical control subjects identified through electronic medical records.
| Arm | Type | Receives |
|---|---|---|
| Ketamine and Esketamine Treatment | Other | Drug: Ketamine, Drug: EsketamineAll study subjects will receive intravenous (IV) ketamine and intranasal (IN) esketamine treatment. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Inpatient at a psychiatric unit (or MGH medical unit, awaiting transfer to psychiatry).
- Male and female, 18-70 years of age, inclusive, at screening.
- Diagnosis of MDD, single or recurrent, and currently experiencing a major depressive episode (MDE) at least eight weeks in duration, prior to screening, according to the criteria defined in the Diagnosis and Statistical manual of Mental Disorders, Fifth Edition (DSM-5). The diagnosis of MDD will be made by a site psychiatrist and supported by the Mini-International Neuropsychiatric Interview (MINI).
- Suicidal ideation determined by a minimum score of 1 on item 12 of the QIDS-C assessment and based on admission to the inpatient unit for suicidal thoughts or behaviors.
- In good general health, as ascertained by medical history. If needed to verify health status, the investigator may order/conduct physical examination (PE) (including measurement of supine and standing vital signs), clinical laboratory evaluations, or ECG.
Key exclusion criteria (22 listed)
- Any history of previous treatment with IV ketamine.
- Pregnant or breastfeeding.
- Subject of childbearing potential who is not willing to use birth control during the study.
- Unstable medical illness, i.e., severe liver or kidney disease, uncontrolled hypertension, uncontrolled hyperthyroidism
- Current diagnosis of a moderate to severe substance use disorder (excluding mild or moderate alcohol or cannabis use disorder which will be permitted), within the last six months prior to screening based on DSM-5 criteria.
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 |
|---|---|---|
| KetamineStudy participants will start treatment including two ketamine infusion visits per week during the acute phase, for up to eight ketamine infusion visits. Participants will then be transitioned to maintenance with intranasal esketamine. | Drug | Ketamine and Esketamine Treatment |
| EsketamineAfter one month from the eighth ketamine infusion visit, participants will initiate weekly esketamine for 12 weeks, for a total of 13 esketamine treatments. The esketamine visits will happen as per standard of care at the clinic and as instructed by the SPRAVATO Risk Evaluation and Mitigation Strategy. | Drug | Ketamine and Esketamine Treatment |
Primary outcome
Feasibility - Retention
Time frame: 24 weeks
For examining the feasibility of treatment with ketamine and esketamine, descriptive analyses will be conducted to assess participants' retention across study visits.
Feasibility - Drop-out Rates
Time frame: 24 weeks
For examining the feasibility of treatment with ketamine and esketamine, descriptive analyses will be conducted to assess participants' drop-out rates across participation in the study.
Tolerability - Cognitive Function and Side Effects
Time frame: Weeks 0, 1, 2, 3, 4, 8, and 12-24
In regard to tolerability, the investigators will closely monitor cognitive functions and side effects during the administration of ketamine and esketamine.
Tolerability - Dosage of Treatment
Time frame: Change between weeks 0, 4, 6, 8, 10, 12, 14, 16, 20, 22, and 24
In regard to tolerability, the investigators will record the Necessary Clinical Adjustments (NCAs) for dosage of ketamine and esketamine treatments.
Tolerability - Frequency of Treatment
Time frame: Change between weeks 0, 4, 6, 8, 10, 12, 14, 16, 20, 22, and 24
In regard to tolerability, the investigators will record the Necessary Clinical Adjustments (NCAs) for the frequency of ketamine and esketamine administration.
6 secondary outcomes
Efficacy - Treatment Response
Time frame: Weeks 4, 8, and 12-24
Efficacy - Trajectory of Suicidal Ideation
Time frame: 24 weeks
Efficacy - Trajectory of Depression
Time frame: 24 weeks
Efficacy - Hospital Readmission Rates
Time frame: 24 weeks
Efficacy - Prevalence of Suicidal Behavior
Time frame: 24 weeks
Efficacy - Healthcare Utilization
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
- Individual participant dataSharing planned: No. The investigators do not plan to share IPD.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine and Esketamine in people with Major Depressive Disorder, run by Massachusetts General Hospital 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 12 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 12 Dec 2025. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cristina Cusin, MD (617-724-5510, mghketamindstudy@partners.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility - Retention (time frame: 24 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Dec 2025.