The OBSERVE Protocol

September 2, 2026 updated by: Yale University

Comparative Effectiveness of Racemic Ketamine Versus Esketamine (Spravato®) for Depression: The OBSERVE Protocol

This observational protocol is intended to provide long-term follow-up data on patients initiating or continuing treatment with either Spravato® or IV ketamine. This can provide us information on the patient acceptability and satisfaction, patterns of use, long-term effectiveness, and safety of the two approaches.

This 5-year, 6-site study will enroll 450 total patients. The sites will comprise 3 academic medical centers and 3 community psychiatric practices.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

450

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Connecticut
      • Milford, Connecticut, United States, 06461
        • Recruiting
        • Mood Institute
        • Contact:
        • Principal Investigator:
          • Lisa Harding, MD
      • New Haven, Connecticut, United States, 06512
        • Recruiting
        • Yale School of Medicine
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University
        • Contact:
          • Brandon Kitay, MD, PhD
          • Phone Number: 404-712-6939
    • Michigan
      • Ann Arbor, Michigan, United States, 48104
        • Active, not recruiting
        • University of Michigan
    • Oklahoma
      • Moore, Oklahoma, United States, 73160
        • Active, not recruiting
        • LifeStance Health
    • Tennessee
      • Nashville, Tennessee, United States, 37228
        • Recruiting
        • Athena Care
        • Principal Investigator:
          • Amanda Sparks-Bushnell, MD
        • Contact:
    • Texas
      • Bellaire, Texas, United States, 77401
        • Recruiting
        • Houston Center for Advanced Psychiatric Treatment
        • Contact:
          • Sandhya Prashad, MD
        • Contact:
        • Principal Investigator:
          • Sandhya Prashad, MD
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Seattle NTC
        • Principal Investigator:
          • Rebecca Allen, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Study population includes adults ages 18 or older with a diagnosis of major depressive disorder that is refractory to two or more antidepressant trials that have moderate to severe depression based on an initial MADRS score of 25 or greater having recently initiated treatment with appropriate baseline measures obtained (treatment-continuing) or scheduled to initiate standard clinical care (treatment-initiating) with either IV ketamine or Spravato® treatment.

Description

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet the following criteria:

  1. Recently started treatment (within 75 days of screening visit) with IV ketamine or Spravato® as prescribed by a clinician for the treatment of moderate to severe (based on an initial MADRS score ≥ 25) TRD (refractory to two or more antidepressant trials) without psychotic features and having appropriate baseline measures collected before starting treatment. These patients are referred to as treatment-continuing subjects.

    OR

  2. Scheduled to receive standard clinical treatment with IV ketamine or Spravato® as prescribed by a clinician for the treatment of moderate to severe (based on an initial MADRS score ≥ 25) TRD (refractory to two or more antidepressant trials) without psychotic features. These patients are referred to as treatment-initiating subjects.

    In addition, in order to be eligible, an individual must meet all of the following additional criteria:

  3. Adult ages 18 or older
  4. Provision of signed and dated informed consent form prior to any study procedures
  5. Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Diagnosis of bipolar disorder or psychotic disorder (i.e., schizophrenia, schizoaffective disorder)
  2. Other psychiatric comorbidities are permitted so long as depression is the predominant diagnosis
  3. Active or recent (within 12 months) substance use disorder (other than nicotine)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
IV Ketamine
Patients taking IV ketamine
Drug: IV Ketamine
IV ketamine
Spravato
Patients taking Spravato, an intranasal form of ketamine
Drug: Spravato
Intranasal esketamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TSQM-9
Time Frame: baseline to 6 months
9-Item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Analyses will be done for the whole sample as well as for treatment-continuing patients who recently completed a randomized trial of ketamine v. esketamine (EQUIVALENCE). The primary analysis for this measure will analyze treatment-continuing patients. Scores range from 0 - 100 with higher scores indicating higher satisfaction.
baseline to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Depression Severity (Self Report)
Time Frame: baseline to 6 months
Change in 16-Item Quick Inventory of Depressive Symptomatology (QIDS). Score ranges from 0 - 27, with higher scores indicating worse depression.
baseline to 6 months
Depression Severity (Clinician Report)
Time Frame: baseline to 6 months
Change in Montgomery-Åsberg Depression Rating Scale (MADRS). Scores range from 0 - 60, with higher scores indicating worse depression.
baseline to 6 months
Measure of Treatment Patterns: Number of treatments
Time Frame: baseline to 6 months
Total number of treatments (ketamine or esketamine) during the study
baseline to 6 months
Measure of Treatment Patterns: Reasons for Discontinuation
Time Frame: baseline to 6 months
Number and proportion of patients who discontinue treatment
baseline to 6 months
Measure of Treatment Patterns: Average Dose
Time Frame: baseline to 6 months
Descriptive measures of average dose of ketamine / esketamine
baseline to 6 months
Measures of Adverse Events
Time Frame: Baseline to 6 months
Total number of serious adverse events possibly related to IV ketamine or esketamine
Baseline to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

Patient-Centered Outcomes Research Institute

Investigators

  • Principal Investigator: Samuel Wilkinson, MD, Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 21, 2024

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

December 5, 2024

First Submitted That Met QC Criteria

December 5, 2024

First Posted (Actual)

December 10, 2024

Study Record Updates

Last Update Posted (Actual)

September 3, 2026

Last Update Submitted That Met QC Criteria

September 2, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000038673
  • 23-005287 (Other Grant/Funding Number: PCORI)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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