About a third of people with depression do not respond fully to standard antidepressants, and research is finally producing options that work differently from older drugs. Ketamine, esketamine nasal spray, and a new postpartum depression pill are already approved, and psilocybin and other rapid-acting treatments are advancing through trials.
What's actually going on in research
Studies are testing fast-acting drugs that work in hours rather than weeks, structured psychedelic therapy with psilocybin, brain stimulation approaches like accelerated TMS, and digital therapy programs. Researchers are also looking at depression in specific groups — postpartum, adolescents, older adults, and people whose depression has resisted multiple treatments.
Fast-acting treatments
Drugs like ketamine and esketamine can lift severe depression within hours, and newer options are being tested. They are aimed at people who have not responded to standard antidepressants.
Psychedelic therapy
Psilocybin combined with talk therapy is being studied for treatment-resistant depression. Early trials show meaningful and sometimes lasting improvement after just a few sessions.
Brain stimulation
Newer forms of TMS deliver a full course in days instead of weeks, and trials are testing deeper stimulation for severe cases. These options avoid medications and their side effects.
What to know before you search
Eligibility often depends on severity, how many treatments have already been tried, and whether the depression is part of bipolar disorder, postpartum, or another specific situation.
What types of trials are currently open
- New medication trials — Testing antidepressants that work through new pathways, including fast-acting drugs for severe or treatment-resistant depression.
- Therapy trials — Testing structured talk therapy programs, often delivered in person, online, or through apps.
- Device trials — Studies of brain stimulation devices like TMS or implanted stimulators for hard-to-treat depression.
- Psychedelic-assisted therapy trials — Testing supervised psilocybin or related treatments combined with therapy sessions.
- Prevention trials — Testing approaches to prevent depression after childbirth, illness, or other high-risk life events.
Recently added Depression trials
Online Personalized Psychological Intervention for Patients With Heart Disease and Depression or Anxiety (MY-CHOICE)
The goal of this feasibility study is to assess if the personalised online psychological intervention MY-CHOICE is acceptable to adults with ischemic heart disease and anxiety or depression. It will also examine the reasons for drop-out. The main questions the study aims to answer are: How many participants complete the intervention and what are the reasons for drop-out. And what are the pre-post change scores on anxiety and depression. Participants will: Complete the MY-CHOICE intervention consisting of 6-12 weeks with online modules on various topics based on individual needs in combination with video- or telephone calls with a therapist (psychologist or a trained master student in Psychology) on a need-to basis. Answer a set of questionnaires pre and post intervention. Participate in a brief interview post intervention.
Coaching as an Adjunct to Ketamine Therapy for Treatment-Resistant Depression
This study is being conducted at Massachusetts General Hospital (MGH) to explore whether adding psychedelic coaching can enhance the effects of ketamine or esketamine maintenance treatment in individuals with treatment-resistant depression (TRD). The investigators are currently enrolling participants who are receiving ongoing maintenance intravenous (IV) ketamine or intranasal esketamine (Spravato) treatment at the MGH Ketamine Clinic. Participation in the study will involve adding coaching sessions to your existing ketamine maintenance treatment.
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