Depression affects more than 20 million adults in the United States each year. Current treatments include SSRIs and SNRIs (antidepressants that adjust brain chemistry), psychotherapy, and newer options like esketamine nasal spray and transcranial magnetic stimulation. Many people improve with these treatments, but about one-third don't respond adequately to standard approaches.
What's actually going on in research
Trials are testing psychedelics like psilocybin that may work in days rather than weeks, faster-acting oral drugs that target different brain pathways than SSRIs, and digital tools that aim to predict which treatment will work best for each person. Researchers are also studying inflammation's role in depression and testing anti-inflammatory approaches.
Psychedelic-assisted therapy
Psilocybin and MDMA are being tested in supervised therapy sessions for treatment-resistant depression. Early results show rapid improvement in some people who haven't responded to standard antidepressants.
Rapid-acting antidepressants
New drugs targeting NMDA receptors and other pathways aim to lift depression within days, not the 4-6 weeks typical for SSRIs. Esketamine was FDA-approved in 2019 for treatment-resistant depression.
Inflammation and depression
Studies are testing whether anti-inflammatory drugs can help people whose depression involves high inflammation markers. This approach may explain why some people don't respond to standard antidepressants.
What to know before you search
Eligibility typically depends on depression severity, whether you've tried other treatments, current medications, and whether you have other mental health or medical conditions.
What types of trials are currently open
- Treatment trials — Testing new antidepressants or comparing existing ones to see which work better or faster for different types of depression.
- Psychedelic trials — Studies of psilocybin, MDMA, or other psychedelics combined with therapy sessions, typically for people who haven't responded to standard treatment.
- Brain stimulation trials — Testing transcranial magnetic stimulation, electroconvulsive therapy, or newer stimulation methods that target specific brain circuits.
- Combination trials — Testing whether combining medications, or pairing medication with specific types of therapy, works better than either alone.
- Digital health trials — Studies using apps, online therapy, or artificial intelligence tools to deliver treatment or predict which treatment will work best.
Recently added Depression trials
EEG Microstate Parameters and Neuroinflammatory Biomarkers in Patients With Treatment-Resistant Major Depressive Disorder Receiving ECT
This study aims to investigate the neurophysiological and inflammatory changes associated with electroconvulsive therapy (ECT) in patients diagnosed with Major Depressive Disorder who are resistant to at least two antidepressant treatments, using microstate analysis derived from resting-state electroencephalography (EEG) recordings. Within this scope, EEG recordings obtained before and after ECT will be compared to determine the relationships between changes in microstate parameters and inflammatory marker levels, clinical variables, and psychometric scale scores reflecting clinical improvement. Peripheral blood samples collected from the same patient group will be analyzed for complete blood count parameters as well as levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), soluble glycoprotein 130 (sgp-130), soluble interleukin-6 receptor (sIL-6R), interferon gamma-induced protein 10 kDa (IP-10), and C-reactive protein (CRP). In addition, inflammatory indices, including the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR), will be calculated. The association between baseline levels of these biomarkers and treatment response will be evaluated. Moreover, changes in biomarker levels following ECT will be statistically examined in relation to clinical scale scores and EEG microstate parameters. Although microstate analysis and inflammatory biomarkers have each been extensively investigated in psychiatric disorders, studies evaluating these two biomarkers together, particularly with the inclusion of healthy control participants, remain limited. In this regard, the present study aims to evaluate the effects of ECT on patients with treatment-resistant depression using objective neurophysiological indicators, to contribute to the understanding of the pathophysiology of depression at the level of brain networks, and to provide a scientific basis for the development of personalized treatment approaches in the future.
Receive a brain implant to treat severe bipolar depression
This study addresses a critical unmet need in the treatment of bipolar disorder by investigating whether Subcallosal Cingulate (SCC) Deep Brain Stimulation (DBS) can safely and effectively treat treatment-resistant bipolar depression without inducing manic switches. The researchers propose to accomplish this by incorporating monitoring of the SCC local field potentials (LFP) for depression tracking and amygdala LFP monitoring for mania prediction while treating Bipolar I patients with SCC DBS Stimulation. This approach could establish a new paradigm for personalized neuromodulation therapy that uses real-time neural monitoring to optimize outcomes while minimizing risks. By incorporating bilateral, dual-site LFP monitoring from both the SCC and amygdala, this research will allow the researchers to assess the therapeutic efficacy of continuous SCC-DBS and develop novel safety biomarkers that could transform the clinical management of DBS therapy in psychiatry. The findings will have immediate implications for clinical practice and will advance the study team's fundamental understanding of the neural circuits underlying mood regulation and dysregulation in bipolar disorder.
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