Major depressive disorder affects roughly 1 in 15 adults in a given year. Treatment options include SSRIs, SNRIs, atypical antidepressants, therapy, and brain stimulation methods like TMS and ECT. About a third of people don't respond adequately to first-line antidepressants, driving research into faster-acting options and new biological targets.
What's actually going on in research
Trials are testing drugs that work through different pathways than SSRIs—including ketamine-like glutamate modulators, psychedelics like psilocybin, anti-inflammatory agents, and drugs targeting the opioid system. Studies are also exploring digital therapeutics, neuromodulation devices, and biomarkers that might predict which treatment will work for whom.
Rapid-acting antidepressants
Esketamine nasal spray gained FDA approval in 2019 for treatment-resistant depression, working within hours instead of weeks. Several trials are testing oral ketamine-like drugs and other glutamate modulators that aim for similar speed without the infusion or clinic visit requirement.
Psychedelic-assisted therapy
Psilocybin is in Phase 3 trials for treatment-resistant depression, combining one or two supervised dosing sessions with therapy. MDMA-assisted therapy is being studied for depression with trauma, and other psychedelics are in earlier testing.
Inflammation targets
Some depression appears driven by inflammation, and trials are testing anti-inflammatory drugs and monoclonal antibodies in people with elevated inflammatory markers. Early studies suggest this approach may help a subset of patients who haven't responded to standard antidepressants.
What to know before you search
Eligibility usually depends on depression severity scores, number of failed treatments, current medications, and absence of bipolar disorder or active substance use.
What types of trials are currently open
- Medication trials — Testing new antidepressants or repurposed drugs, often in people who haven't responded to at least two prior treatments. May involve pills, nasal sprays, or infusions.
- Psychedelic trials — Supervised dosing sessions with psilocybin, MDMA, or other psychedelics, combined with therapy before and after. Typically requires in-person visits and psychological screening.
- Device trials — Testing brain stimulation methods like TMS, tDCS, or vagus nerve stimulation. Usually involves daily or weekly sessions over several weeks.
- Therapy trials — Studies of cognitive behavioral therapy, interpersonal therapy, or newer approaches, sometimes delivered digitally or combined with medication.
- Biomarker studies — Following people through treatment to identify blood tests, brain imaging, or genetic markers that predict response. May involve extra visits for scans or blood draws.
Recently added Major Depressive Disorder trials
Take a new depression medication being tested in adults
The goal of this clinical trial is to learn if a drug called TNX-102 SL works to treat moderate to severe major depressive disorder in adults. It will also learn about the safety of TNX-102 SL. The main questions it aims to answer are: Does TNX-102 SL improve depression symptoms according to a depression symptom rating scale? What medical problems do participants have when taking TNX-102 SL? Researchers will compare TNX-102 SL to a placebo (a look-alike substance that contains no drug) to see if TNX-102 SL works to treat major depressive disorder. Participants will: Take TNX-102 SL or a placebo every night at bedtime for 6 weeks Visit the clinic once every 2 weeks for checkups and tests
Try group-based therapy for depression, anxiety, or stress
This clinical study investigates the effectiveness of two psychological treatment formats for young people aged 16-25 with symptoms of depression, anxiety, stress, or interpersonal difficulties. The study compares group-based Acceptance and Commitment Therapy (ACT) with treatment as usual (TAU), most frequent that would be individual psychotherapy, both of which are established treatment approaches. The study uses a randomized controlled design (RCT), in which participants are randomly assigned to one of the two treatment conditions. This allows for a systematic comparison of treatment outcomes between ACT delivered in a group format and standard individual therapy. The ACT group intervention consists of a structured program in which participants meet regularly over a defined treatment period. The treatment focuses on processes such as psychological flexibility, acceptance of internal experiences, and engagement in actions aligned with personal values. The individual therapy condition consists of one-to-one sessions with a clinician, following standard therapeutic practice. Treatment content and duration are tailored to the participant's clinical presentation and therapeutic needs. Outcome measures include standardized assessments of mental health symptoms, functioning, and psychological processes. These assessments are conducted at baseline, during the treatment period, at post-treatment, and at follow-up time points. Data collected from these measures will be used to evaluate changes over time and differences between the two treatment conditions. The primary aim of the study is to determine whether group-based ACT is as effective as, or more effective than, individual psychotherapy for young people receiving mental health services. The results are expected to contribute to improved knowledge about treatment options for this age group and inform future clinical practice.
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