About a third of people with major depressive disorder (MDD) don't respond fully to standard antidepressants — a pattern called treatment-resistant depression (TRD). Research is finally producing options that work differently from older drugs: esketamine nasal spray and ketamine are FDA-approved for TRD, and zuranolone (a 14-day oral pill) is approved for postpartum depression. Psilocybin, orexin receptor antagonists like seltorexant, and other rapid-acting treatments are advancing through Phase 2 and Phase 3 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
Effects of the Multispecies Probiotic Ecologic Barrier in IBS Patients With Upper GI Symptoms and Anxiety, Depression, or Stress
The aim of this clinical trial is to find out whether Ecologic Barrier is effective in supporting the treatment of irritable bowel syndrome (IBS) in adults. The main questions that this trial aims to answer are: * Does Ecologic Barrier help improve IBS severity when added to standard IBS treatment? * Does Ecologic Barrier help improve symptoms of anxiety, depression, and stress in patients with IBS? * Does Ecologic Barrier help improve upper gastrointestinal symptoms when added to standard IBS treatment? * What adverse events may occur when using Ecologic Barrier? The researchers will compare a group receiving standard symptom-based treatment with another group receiving standard treatment plus Ecologic Barrier. Participants will: * Receive IBS treatment for 2 months, with Ecologic Barrier added during either the first month or the second month, depending on random assignment. * Attend a follow-up visit after 1 month of treatment. * Take part in interviews about IBS severity, symptom improvement, adverse events, and symptoms of depression and anxiety at baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
Pilot Study of a Behavioral Program for Resident Depression in Skilled Nursing Facilities
The goal of this clinical trial is to test a behavioral health program (Interventions for Stressful Transitions in Later Life, InSTILL, for Individuals) for skilled nursing facility residents. The main questions it aims to answer is whether the program is program is feasible, satisfactory, and helpful. Participants will join 6 bi-weekly sessions of the InSTILL program. Participants will complete assessments at three timepoints (all) and a brief-exit interview.
Find Depression trials matched specifically to you
Answer 3 quick questions and we'll show you trials that fit your situation.