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DepressionAugust 2019Summary reviewed May 2026

A Nasal Spray Plus Antidepressant Pill Cut Depression Scores in Half at Four Weeks

TRANSFORM-2 tested esketamine, a nasal spray form of ketamine, in 236 adults with major depressive disorder that hadn't responded to at least two prior antidepressants. After four weeks of esketamine alongside a newly started oral antidepressant, depression scores improved more than with the antidepressant alone — and many patients felt better within the first 24 hours.

What the trial was testing

The TRANSFORM-2 enrolled 236 patients with depression. The study was sponsored by Janssen Research & Development and tracked outcomes across the full group of patients who matched the trial's eligibility profile.

It was a large trial designed to confirm whether the treatment works well enough for wider use. Trials at this stage are designed to produce evidence regulators and physicians can act on — not just observations to follow up later.

What the results showed

4 points greater improvement on depression scales at 4 weeks vs. antidepressant alone.

American Journal of Psychiatry · 2019 · NCT02418585

These findings — that greater improvement on depression scales at 4 weeks with esketamine + a new oral antidepressant — were published in the American Journal of Psychiatry and represent the headline result of the study.

Researchers tracked outcomes across 236 patients enrolled in the trial. The result was consistent enough across the group that the team felt confident reporting it.

What this means for patients

For patients with depression, this result changes the calculus on what to ask their care team about. Whether it changes day-to-day care depends on factors like disease subtype, prior treatments, and where the patient is in their care journey.

What you can do now

Esketamine (Spravato) is FDA-approved for treatment-resistant depression and for depression with active suicidal thoughts. Sessions happen at certified clinics under medical supervision (~2 hours each), starting twice weekly and tapering. Ask your psychiatrist whether you'd qualify if at least two antidepressants haven't worked for you.

Eligibility for the treatments mentioned above depends on specific test results and clinical history. Bring this summary, the trial name, and your most recent labs or pathology report to your next visit.

Open depression trials

RecruitingInterventional study

Creating Health Course Study for People With Rheumatological Conditions and Mood Disorders

The goal of this project is to critically evaluate the effectiveness of an online health program designed to improve diet and self-care in patients with rheumatological conditions, including rheumatoid arthritis (RA), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), psoriatic arthritis (PsA), anxiety disorders, depressive disorders and moderate depression. Additionally, investigators will assess the program's effectiveness, as well as the challenges and facilitators involved in using an online wellness program to reduce fatigue and enhance the quality of life in patients suffering from these conditions.

Iowa City, Iowa, United States
RecruitingInterventional study

Activating Social Resources in Psychotherapy-Seeking Individuals: Effectiveness and Timing of a Social Support Just-in-Time Adaptive Intervention

This study evaluates a Just-In-Time Adaptive Intervention (JITAI) aiming to foster social support processes for adults with elevated depressive symptoms awaiting outpatient psychotherapy. Utilizing a daily-level micro-randomized trial (MRT) design conducted over 21 days, participants are assessed six times daily. Participants are randomized across four conditions: (1) vulnerability-triggered, (2) vulnerability and receptivity-triggered, (3) support-need-triggered, and (4) a no-intervention control. The primary objective of this study is to evaluate the effectiveness of the JITAI in reducing daily depressive symptoms and increasing received social support (primary outcomes), as well as reducing daily loneliness and enhancing perceived social support (secondary outcomes). Furthermore, the study aims to compare the relative efficacy of three distinct triggering strategies to identify the most effective timing for intervention delivery.

Zurich, Canton of Zurich, Switzerland