Clinical trials
Treatment-Resistant Major Depressive Disorder clinical trials
Below are recruiting treatment-resistant major depressive disorder clinical trials, each written for real people, not researchers. We’re tracking 71 recruiting studies, each written for real people, not researchers, below.
Recruiting studies
- NCT05661383Recruiting
Smell and brain stimulation for hard-to-treat depression
This trial studies whether stimulating the brain and senses related to smell can reduce symptoms in people with depression that has not responded to usual treatment. It may help by testing new non-drug approaches for improving mood and motivation.
BronAges 18 years+ - NCT05773755Recruiting
Brain stimulation surgery for treatment-resistant depression
This trial studies whether deep brain stimulation (DBS)—a surgically placed brain device—can reduce severe, long-lasting depression that hasn’t responded to many treatments. It may help people whose depression has persisted despite trying multiple antidepressant and other evidence-based therapies.
New York, New YorkAges 25–70 - NCT05798143Recruiting
Testing brain-signal biomarkers in treatment-resistant depression
This trial studies signs in the brain (biomarkers) during an accelerated form of nerve stimulation to treat depression that hasn’t improved with usual antidepressants. It may help researchers learn who benefits and how to better personalize treatment.
ChietiAges 18–65 - NCT05833087Recruiting
Schema therapy for long-lasting, hard-to-treat depression
This study tests whether schema therapy can help people with chronic depression that hasn’t improved enough with standard antidepressant treatments. You’d be in a psychiatric clinic and be assessed for severity and diagnosis, then receive the therapy being studied.
Ballerup MunicipalityAges 18–65 - NCT06085950Recruiting
Ultrasound brain stimulation for hard-to-treat depression
This trial tests whether a gentle ultrasound treatment aimed at the brain can help people with severe depression that hasn't improved with at least two prior medications. It's a first small study to see if the approach is safe and promising.
ParisAges 18–75 - NCT06132178RecruitingPhase 2
Psilocybin and rTMS for hard-to-treat depression
This study tests whether a combination of psilocybin (a psychedelic substance) and transcranial magnetic stimulation (rTMS, a noninvasive brain stimulation) can help people with treatment-resistant depression. It involves daily visits to the research center for about 2 weeks.
Austin, TexasAges 22–65 - NCT06163625Recruiting
Brain activity and memory in treatment-resistant depression
This study looks at how the brain's frontal lobe (DLPFC) works during memory tasks in people with treatment-resistant depression. It compares brain activity between depressed patients and healthy controls using MRI and possibly a brain stimulation technique (rTMS). It aims to understand why some people don't respond to standard treatments.
Toronto, OntarioAges 18–65 - NCT06218030RecruitingPhase 4
L-methylfolate for treatment-resistant anxiety
This study tests whether adding L-methylfolate (a form of vitamin B9) to your current antidepressant can help with generalized anxiety disorder that has not responded to other treatments. It is for adults who are already on a stable dose of an SSRI or SNRI medication.
Kingston, OntarioAges 18–65 - NCT06278909Recruiting
Nerve stimulation for stubborn anxiety
This study tests a new, non-invasive treatment using mild electrical stimulation on a nerve in your face (trigeminal nerve) to help with anxiety that hasn't improved with other treatments. It aims to see if this approach is safe and helpful for people with generalized anxiety disorder who have not responded to standard medications.
Kingston, OntarioAges 18–65 - NCT07696871RecruitingPhase 1/Phase 2
Cannabidiol oil for treatment-resistant depression
This trial tests if cannabidiol (CBD) oil can help people with major depression that has not improved with standard antidepressants. You will take CBD oil or a placebo while continuing your current antidepressant treatment to see if it improves your symptoms.
Tubarão, Santa CatarinaAges 18–69 - NCT06378229RecruitingPhase 2
Psilocybin for hospitalized treatment-resistant depression
This trial tests whether a single dose of psilocybin can help hospitalized patients with tough-to-treat depression. It focuses on people who haven't improved with standard antidepressants and need a new option.
Ghent, Oost-VlaanderenAges 18 years+ - NCT06396312Recruiting
Predicting lithium response in difficult depression
This study looks at how to predict which people with hard-to-treat depression will benefit from adding lithium to their antidepressant. If you have treatment-resistant depression and are considering lithium, this trial may help find the best treatment for you.
Munich, BavariaAges 18 years+ - NCT06404320Recruiting
Exercise program for treatment-resistant depression
This study tests whether a physical activity program can help adults whose depression hasn’t improved after trying at least two antidepressants. If you’re sedentary, between 18 and 65, and have treatment-resistant depression, this program might offer a new way to feel better through exercise.
Toronto, OntarioAges 18–65 - NCT06480500RecruitingPhase 2
Online therapy and IV ketamine for severe depression with suicide risk
This study tests whether adding an online therapy (i-CBT) to intravenous (IV) ketamine is better than IV ketamine alone for people with treatment-resistant depression who are also thinking about suicide. You'll receive either ketamine or a comparison drug (midazolam), plus the online therapy, in a hospital setting.
Toronto, OntarioAges 21–65 - NCT06511544Recruiting
Brain stimulation for treatment-resistant depression with rumination
This study tests whether a specific form of brain stimulation (called rTMS) can help people with treatment-resistant depression by targeting brain circuits linked to rumination (repetitive negative thinking). If you have tried at least one antidepressant without success and do not have other major mental health conditions, this trial may be worth exploring with your doctor.
Indianapolis, IndianaAges 18–70 - NCT06511908RecruitingPhase 2
Testing a new ketamine-like drug for hard-to-treat depression
This study tests a new experimental drug (2R,6R)-HNK, a chemical related to ketamine, given by IV infusion to see if it can help people with depression that hasn't improved with other treatments. The goal is to find a new option for people who have not found relief from standard antidepressants.
Bethesda, MarylandAges 18–70 - NCT06512220RecruitingPhase 2
Psilocybin for treatment-resistant depression brain imaging study
This study tests whether a psilocybin-based treatment can help people with depression that has not improved after trying several antidepressants. You will receive the study treatment and have brain scans to see how it affects brain connections.
Toronto, OntarioAges 18–65 - NCT06542094Recruiting
Brain stimulation for severe depression that hasn't improved with other treatments
This trial tests if deep brain stimulation (a device that sends tiny electrical pulses to mood-related brain areas) can help people with tough-to-treat depression. It uses brain-signal monitoring to see which patterns predict improvement.
Chengdu, SichuanAges 18–65 - NCT06547489RecruitingPhase 2
Testing zelquistinel for major depression
This study tests whether zelquistinel, an investigational drug, can reduce symptoms of major depressive disorder (a type of clinical depression). It is for people who are currently experiencing a moderate to severe depressive episode and are not taking other antidepressants.
Birmingham, AlabamaAges 18–64 - NCT06599099Recruiting
Deep brain stimulation for depression that hasn't responded to other treatments
This trial tests if deep brain stimulation (a surgical implant that sends gentle electrical pulses to a specific area of the brain) can help people with bipolar I disorder who are currently in a severe depressive episode and have not found relief from multiple treatments.
Boston, MassachusettsAges 22–64 - NCT06668571RecruitingPhase 2
Ketamine for treatment-resistant depression
This study tests if intravenous ketamine can help people with treatment-resistant depression who haven't found relief from at least two other treatments. If you qualify, you'll receive ketamine infusions to see if it improves your mood.
Rochester, MinnesotaAges 18–65 - NCT07684911Recruiting
Long-term effects of TMS for depression
This study looks at how well the benefits of transcranial magnetic stimulation (TMS) last over time for people with depression that didn't get better with other treatments. It also uses brain scans to find markers that might predict who will keep doing well.
RennesAges 18 years+ - NCT07611773Recruiting
Brain Stimulation for Depression Treatment Planning
This study tests whether brain scans can predict which people with depression will benefit from transcranial direct current stimulation (tDCS)—a non-invasive treatment that uses mild electrical pulses to stimulate brain areas related to mood. You would use a small home device and complete brain monitoring sessions.
ValenciaAges 18 years+ - NCT06732089Recruiting
Digital help for stubborn depression
This trial tests a digital program (smartphone app or website) to help people with tough-to-treat depression. If you are already receiving advanced treatments like rTMS, ketamine, or ECT at St. Michael's Hospital, you may be able to join and see if this extra digital support improves your mood.
Toronto, OntarioAges 18 years+
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Common questions
- Are there clinical trials for treatment-resistant major depressive disorder?
- Yes. Clin2 currently lists 71 recruiting treatment-resistant major depressive disorder studies from the U.S. registry, each rewritten for real people, not researchers, so you can see what it’s testing and who it’s for.
- How do I know if I qualify for a treatment-resistant major depressive disorder trial?
- Each study lists its eligibility criteria — rules about age, diagnosis, and prior treatments. On every Clin2 trial page we explain these in words written for real people and offer a short, optional pre-screen for a fit read. The study team makes the final decision.
- Does it cost anything to join a treatment-resistant major depressive disorder trial?
- Using Clin2 is always free. Many trials cover the cost of the study treatment and related visits; some reimburse travel. The study team explains exactly what’s covered before you decide.
Related conditions
Clin2 helps you find and understand clinical trials and does not provide medical advice. Study data comes from ClinicalTrials.gov. Talk with your doctor about whether a specific trial is right for you.