Depression is one of the most common mental health conditions, affecting roughly one in six adults at some point in life. First-line treatments include antidepressants like SSRIs and SNRIs, talk therapy, or both. Many people respond to these approaches, but roughly a third don't improve enough even after trying multiple medications.
What's actually going on in research
Trials are testing fast-acting drugs like esketamine nasal spray and psychedelics, new pills that work differently than SSRIs, brain stimulation methods that don't require surgery, and digital tools that predict which treatment might work best for each person. Researchers are also studying inflammation's role in depression and testing anti-inflammatory approaches.
Psychedelics
Psilocybin showed benefits in recent trials and received FDA breakthrough designation for treatment-resistant depression. MDMA-assisted therapy is moving through late-stage trials for PTSD with depression.
Inflammation-targeted treatments
Studies suggest inflammation drives depression in some people. Trials are testing whether anti-inflammatory drugs or drugs that block specific immune signals can help people who haven't responded to standard antidepressants.
Precision matching
Researchers are developing tests that use brain scans, genetic markers, or blood tests to predict which antidepressant will work for a given person. The goal is to shorten the trial-and-error period many people face.
What to know before you search
Eligibility typically depends on depression severity, number of prior treatments tried, and whether symptoms meet specific criteria for major depressive disorder.
What types of trials are currently open
- Medication trials — Testing new antidepressants or new uses of existing drugs, often comparing them to placebo or standard SSRIs.
- Treatment-resistant trials — For people who haven't improved after trying two or more antidepressants. May test add-on drugs, brain stimulation, or novel mechanisms.
- Psychedelic trials — Testing psilocybin, MDMA, or related compounds, usually with therapy sessions before and after dosing.
- Brain stimulation trials — Testing methods like transcranial magnetic stimulation or newer non-invasive approaches that target specific brain circuits.
- Digital health trials — Testing apps, online therapy programs, or tools that use data to predict treatment response.
Recently added Depression trials
Unveiling Maternal-fetal BRAin-body Interactions in Pregnant WOmen Affected by Depression
The goal of this study is to learn how depression during pregnancy is linked to changes in the brain and body of the mother and to the development of the baby, in pregnant women with major depressive disorder (MDD) and pregnant women without depression. The main questions it aims to answer are: * How common is major depressive disorder during pregnancy in a European multi-site cohort? * Do pregnant women with MDD show differences in hippocampal volume compared with pregnant women without depression? * Do maternal blood, placenta, cord blood, brain imaging and heart activity measures, and the brain and development of the babies, differ between the two groups? Pregnant women will be screened within the 20th week of pregnancy and assigned to the MDD group or to the control group based on a structured clinical interview. They will not receive any study drug: women with depression will receive the usual care recommended by clinical guidelines. Participants will: * Have clinical, psychiatric and psychological assessments (interviews and questionnaires) at screening, at 22, 26 and 32 weeks of pregnancy, at birth, and at 1 and 6 months after birth * Have a brain MRI with simultaneous EEG-ECG or photoplethysmography (PPG) at about 22 weeks of pregnancy * Have a fetal MRI by 22 weeks and fetal ultrasound scans at 22, 26 and 32 weeks * Give blood samples at 22, 26 and 32 weeks of pregnancy, and a cord blood sample at birth (placenta samples in a subgroup at the Milan center only) Their newborns will have a neurological and visual examination, a brain MRI and an EEG-ECG or PPG recording after birth, and a developmental assessment (Bayley Scales) at 6 months.
Health Assessment in People With Severe Mental Illness
People living with severe mental illness (SMI) experience substantial physical health inequalities, including an increased prevalence of cardiovascular disease, obesity, metabolic disorders, reduced physical fitness, and premature mortality. Physical inactivity, prolonged sedentary behavior, sleep disturbances, and the metabolic effects of psychiatric medications may contribute to these health problems. The PHASMI study aims to provide a comprehensive assessment of physical health, cardiorespiratory fitness, cardiometabolic risk, physical functioning, lifestyle characteristics, emotional well-being, and health-related quality of life in adults with severe mental illness. The primary objective is to investigate associations between sociodemographic, clinical, and lifestyle characteristics and cardiorespiratory fitness, assessed through peak oxygen uptake (VO2peak). PHASMI is an observational, descriptive, cross-sectional study conducted in Álava, Spain. The anticipated sample comprises 275 adults aged 18 to 65 years with a diagnosis of severe mental illness according to DSM-5 criteria established by psychiatry specialists. Participants will be recruited through the Mental Health Network of Álava, including individuals receiving community-based psychiatric care and hospitalized patients. Participants will undergo a comprehensive health assessment involving cardiopulmonary exercise testing on a treadmill using a modified Bruce protocol, the Modified Shuttle Walk Test, anthropometric measurements, body composition analysis, blood pressure measurements, electrocardiography, laboratory analyses, handgrip strength testing, and standardized assessments of physical functioning. Physical activity, sedentary behavior, and sleep will be assessed using standardized questionnaires and a wrist-worn ActiGraph GT3X+ accelerometer over eight consecutive days. Emotional well-being and health-related quality of life will be evaluated using validated questionnaires. The main in-person assessments will be conducted over two consecutive days at the University of the Basque Country and the Psychiatric Hospital of Álava. Written informed consent will be obtained before participation. No experimental treatment or therapeutic intervention will be assigned. By examining associations between physical fitness, cardiometabolic health, lifestyle characteristics, and psychological well-being, PHASMI seeks to identify potentially modifiable factors associated with poorer physical health and inform future prevention and health promotion strategies for people living with severe mental illness.
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