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RecruitingDepression

PCORI Comparative Effectiveness Study-Esketamine (Spravato) vs. Ketamine-Equivalence Study

Eligible age

18+ yrs

Accepts

All genders

Locations

5 states

Healthy volunteers

No

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About this study

The purpose of this study is to compare the relative effectiveness, acceptability, and side effects of ketamine delivered through an IV (a drip into the arm) which is not currently FDA approved for use in the treatment of treatment-resistant depression (TRD) and Esketamine (Spravato®), taken as a nasal spray which has received FDA approval for use in the treatment of treatment-resistant depression (TRD) in the treatment of patients with treatment-resistant depression (TRD). The study will look at the following: * How well the treatment helps with symptoms of depression (effectiveness), * How comfortable and willing people are to use the treatment (acceptability), and * How well people can deal with any side effects from the treatment (tolerability). The study will also examine factors that may predict which treatment works better for certain patients.

Sponsor: Yale University

You may qualify if…

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Adults ages 18 or older
  • Diagnosis of major depressive disorder that is refractory to two or more antidepressant trials
  • Moderate or severe depression based on an initial MADRS score ≥ 25
  • Judged appropriate for ketamine or esketamine by clinician, independent of potential study participation
  • A female participant must be:
  • a. Not of childbearing potential\*, OR b. Of childbearing potential and practicing a highly effective method of contraception (failure rate of \<1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until 1 week after last dose - the end of relevant systemic exposure. The investigator will evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of drug. Acceptable methods of contraception are: i. combined (estrogen and progestogen containing) hormonal or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, transdermal, or intravaginal) ii. intrauterine device (IUD) iii. intrauterine hormone-releasing system (IUS) iv. bilateral tubal occlusion/ligation v. male partner with a bilateral vasectomy with documented aspermia or a bilateral orchiectomy vi. male or female condom with spermicide, diaphragm, or sponge with spermicide (Note: Use of condom as the sole method of contraception is not considered to be a highly effective method of contraception).

You may not qualify if…

  • Diagnosis of bipolar disorder or psychotic disorder (i.e., schizophrenia, schizoaffective disorder)
  • Other psychiatric comorbidities are permitted so long as depression is the predominant diagnosis
  • Active or recent (within 12 months) substance use disorder (other than nicotine)
  • Pregnant or lactating women
  • Intracerebral hemorrhage or aneurysmal vascular disease
  • Hypersensitivity to ketamine, esketamine or any of the excipients
  • Known family history of ketamine use disorder
  • Prior known ketamine use disorder as well as subjects for whom study participations will result in more than 8 lifetime exposures to ketamine (e.g., prior exposure to ketamine, prior recreational use with ketamine). Prior esketamine exposure is also exclusionary.

Where it's recruiting

Connecticut

Milford · New Haven

Georgia

Atlanta

Michigan

Ann Arbor

Texas

Bellaire

Source: ClinicalTrials.gov · NCT06713616 · last updated 2026-05-05