Ongoing Clinical Trials for Major Depression

There are currently 41 clinical trials recruiting patients with Major Depression (also known as Major Depressive Disorder, MDD, Clinical Depression, Unipolar Depression). These studies are investigating various treatments including novel medications, established drugs in new combinations, psychedelic compounds, and brain stimulation techniques, conducted across multiple European countries and other locations worldwide.

Clinical trial locations

• Austria
  • Study on the Effects of Escitalopram and Bupropion on Dopamine Levels in Patients with Major Depression
  • Study on Esketamine and Propofol for Anesthesia in Electroconvulsive Therapy for Patients with Major Depression
  • Study on Enhanced Treatment for Schizophrenia, Depression, and Bipolar Disorder Using Esketamine, Bupropion, and Quetiapine for Patients with Initial Treatment Failure
• Belgium
  • Evaluating NBI-1065845 as an Additional Treatment for Adults with Major Depressive Disorder Who Are Not Responding Adequately to Current Therapy
  • Safety and Tolerability Study of NBI-1065845 as Additional Treatment for Adults with Major Depressive Disorder
  • Study on Minocycline and Celecoxib for Patients with Major Depressive Disorder Not Responding to Antidepressants
  • Study on Aticaprant for Adults with Major Depressive Disorder and Anhedonia Not Responding to Antidepressants
  • Study on Aticaprant and Antidepressant for Preventing Relapse in Adults with Major Depressive Disorder and Anhedonia
  • Study on the Safety and Effectiveness of Aticaprant with Antidepressants for Adults and Elderly with Major Depressive Disorder
  • Testing BI 1569912 for Major Depressive Disorder in Patients Using Antidepressants
• Bulgaria
  • Safety and Tolerability Study of NBI-1065845 as Additional Treatment for Adults with Major Depressive Disorder
  • Study on Lumateperone for Patients with Major Depressive Disorder Not Responding to Antidepressants
  • Study on Seltorexant for Adults and Elderly with Major Depressive Disorder and Insomnia Symptoms
  • Study on the Effects of NMRA-335140 for Adults with Major Depressive Disorder
• Croatia
  • Safety and Tolerability Study of NBI-1065845 as Additional Treatment for Adults with Major Depressive Disorder
  • Study on the Effectiveness and Safety of NBI-1065845 for Adults with Major Depressive Disorder
• Czechia
  • Safety and Tolerability Study of NBI-1065845 as Additional Treatment for Adults with Major Depressive Disorder
  • Study on Seltorexant for Adults and Elderly with Major Depressive Disorder and Insomnia Symptoms
  • Study on the Effects of NMRA-335140 for Adults with Major Depressive Disorder
  • Study on the Effects of Psilocybin (COMP360) for Adults with Treatment-Resistant Depression
  • Study on the Effectiveness and Safety of NBI-1065845 for Adults with Major Depressive Disorder
  • Study on Psilocybin, Ketamine, and Midazolam for Patients with Treatment-Resistant Depression

Evaluating NBI-1065845 as an Additional Treatment for Adults with Major Depressive Disorder Who Are Not Responding Adequately to Current Therapy

This trial is investigating NBI-1065845 as an add-on treatment for adults with moderate or severe Major Depressive Disorder who have not responded well enough to their current antidepressant medication. The study is taking place in Hungary, Latvia, Belgium, and Finland.

Main inclusion criteria: You must be at least 18 years old and have recurrent Major Depressive Disorder that is moderate or severe, or persistent depressive disorder. You need to be taking oral antidepressant medication but experiencing an inadequate response despite proper dosing and duration. Your Hamilton Depression Rating Scale score must be 22 or higher at both screening and on the first day of the study.

Main exclusion criteria: You cannot participate if you have other mental health conditions besides depression, such as bipolar disorder or schizophrenia. You are excluded if you are currently experiencing thoughts of harming yourself or others, have attempted suicide in the past year, or have a history of substance abuse or dependence in the past 6 months. Other exclusions include uncontrolled medical conditions, pregnancy or breastfeeding, and having already tried and failed 4 or more antidepressant treatments for your current episode.

Study focus: The trial evaluates whether NBI-1065845, when added to your existing antidepressant medication, can improve symptoms of depression over an 8-week period. The medication’s effects will be measured using the Montgomery-Asberg Depression Rating Scale and other assessments that evaluate how depression affects your daily functioning.

Investigational drug: NBI-1065845 is an experimental medication taken as tablets. It is designed to work alongside your current depression medication to potentially improve symptoms. Participants will also receive a placebo as a comparison to determine the medication’s effectiveness.

Safety and Tolerability Study of NBI-1065845 as Additional Treatment for Adults with Major Depressive Disorder

This study focuses on evaluating the long-term safety and tolerability of NBI-1065845 when used as an additional treatment alongside existing antidepressants for adults with Major Depressive Disorder. The trial is being conducted across multiple European countries including Poland, Bulgaria, Romania, Lithuania, Netherlands, Czechia, Croatia, Hungary, Slovakia, Latvia, Sweden, Belgium, and Finland.

Main inclusion criteria: You must have been diagnosed with recurrent Major Depressive Disorder (moderate or severe) or persistent depressive disorder. Your current depression treatment with oral antidepressants should not be working well enough. You need to have been taking your medication for at least 8 weeks and be willing to continue taking the same medication at the same dose throughout the 52-week study. Your depression severity score on the MADRS must be 18 or higher when first evaluated.

Main exclusion criteria: You cannot participate if you have bipolar disorder or psychotic disorders. Other exclusions include current substance use disorder within the past 6 months, significant risk of self-harm or suicide, unstable medical conditions, use of medications that could interact with the study drug, pregnancy or breastfeeding, severe liver or kidney problems, history of seizures or epilepsy, and uncontrolled high blood pressure.

Study focus: The trial examines the long-term safety of NBI-1065845 over 52 weeks (one year). Throughout this period, your health and any side effects will be monitored regularly. You will continue taking your current antidepressant medication while also taking the study medication.

Investigational drug: NBI-1065845 is an investigational medication taken as tablets, added to your existing antidepressant treatment. The study aims to determine if it is safe and well-tolerated when used over an extended period for people with depression who haven’t responded adequately to standard treatments.

Study of NBI-1065845 as add-on treatment to prevent depression relapse in adults with Major Depressive Disorder who responded to initial treatment

This trial is studying whether NBI-1065845 can help prevent depression symptoms from returning in adults with Major Depressive Disorder who have shown improvement with treatment. The study is being conducted in Poland, Bulgaria, Estonia, Italy, and Spain.

Main inclusion criteria: You must be at least 18 years old and have a confirmed diagnosis of recurrent Major Depressive Disorder (moderate or severe) or persistent depressive disorder. You need to be currently taking oral antidepressant medications and must have shown inadequate response to previous treatments during your current depression episode. Your Hamilton Depression Rating Scale score must be 22 or higher during screening and on the first day of the study.

Main exclusion criteria: You cannot participate if you have treatment-resistant Major Depressive Disorder (meaning depression that hasn’t improved with at least two different antidepressant treatments). Other exclusions include current diagnosis of other psychiatric conditions besides depression, significant risk of self-harm or suicide, substance abuse or dependence within the past 6 months, serious uncontrolled medical conditions, pregnancy or breastfeeding, use of certain medications that might interfere with the study drug, and history of seizures or other neurological conditions.

Study focus: The trial has two main phases. In the first phase, all participants receive NBI-1065845 along with their current antidepressant to see if they improve. Those who show improvement then move to the second phase, where they are randomly assigned to either continue taking NBI-1065845 or receive a placebo. The main focus is on measuring how long it takes for depression symptoms to return, if they do.

Investigational drug: NBI-1065845 is an experimental medication taken as tablets alongside your existing antidepressant treatment. The study aims to determine if it can help maintain improvements in depression symptoms and prevent relapse after initial improvement. A placebo is also used in the study to compare the effects.

Study on Buprenorphine for Treating Severe Suicidal Thoughts in Patients with Major Depression

This trial is investigating whether buprenorphine, a medication typically used for pain relief, can help reduce severe suicidal thoughts in people experiencing a major depressive episode. The study is taking place in France.

Main inclusion criteria: You must be between 18 and 65 years old and currently hospitalized. You need to have a diagnosis of a current major depressive episode without psychotic features according to DSM-5 criteria, with a Montgomery-Asberg Depression Rating Scale score greater than 20. This can be part of either bipolar or major depressive disorder. You must also have a current Scale for Suicidal Ideation score greater than 8, indicating significant suicidal thoughts.

Main exclusion criteria: While specific exclusion criteria are not fully detailed in the available information, individuals with certain mental disorders other than major depression, those outside the specified age range, and those unable to comply with study procedures would not be eligible. Vulnerable populations who cannot provide informed consent are also excluded.

Study focus: The trial evaluates two different doses of buprenorphine (0.8 mg and 0.4 mg) taken as sublingual tablets (placed under the tongue to dissolve). The primary goal is to assess the effect of buprenorphine compared to placebo on suicidal thoughts at Day 7. Secondary evaluations continue from Day 7 to Day 42, monitoring various aspects including psychological pain, depression scores, suicide attempts, side effects, and brain activity measurements.

Investigational drug: Buprenorphine is being studied for its potential to reduce severe suicidal thoughts during a major depressive episode. The trial aims to determine which dosage is more effective in reducing suicidal ideation when added to standard depression treatment.

Study on Ketamine and Midazolam for Adults with Depression and Alcohol Use Disorder

This trial is examining the effects of ketamine on individuals who have both depression and alcohol use disorder while they are receiving inpatient addiction therapy. The study is being conducted in Norway.

Main inclusion criteria: You must be between 18 and 65 years old and have at least moderate depression without psychotic features. Alcohol dependence must be your primary substance use disorder. You need to be admitted to the hospital for inpatient addiction therapy at University Hospital of North Norway.

Main exclusion criteria: You cannot participate if you are not diagnosed with both depression and alcohol use disorder. Other exclusions include being outside the specified age range, not being admitted for addiction therapy, pregnancy or breastfeeding, and belonging to a vulnerable population with limited ability to protect their own interests.

Study focus: The trial compares the effects of ketamine with midazolam (used as a comparison). Both medications are given as intravenous infusions. The primary outcome is measured by changes in depression symptoms using the MADRS scale from the start of the study to within three days after the final treatment session. Secondary outcomes include changes in alcohol craving, alcohol consumption, neurocognitive function, and any adverse reactions.

Investigational drugs: Ketamine is being studied for its potential to help with depression in adults who also have alcohol use disorder. The trial aims to see if ketamine can effectively reduce symptoms of depression while patients are receiving treatment for addiction. Midazolam is used as a comparison medication.

Study on Lumateperone for Patients with Major Depressive Disorder Not Responding to Antidepressants

This trial is evaluating the effectiveness and safety of lumateperone when used alongside existing antidepressant treatments for individuals with Major Depressive Disorder who have not responded adequately to their current medication. The study is being conducted in Bulgaria, France, Lithuania, and Spain.

Main inclusion criteria: You must provide written informed consent and be between 18 and 65 years old. You need to have Major Depressive Disorder confirmed by a healthcare professional using a special interview process. Your current episode of depression must have started at least 8 weeks ago but not more than 18 months ago, with a moderate level of depression severity. You must be experiencing an inadequate response to your antidepressant treatment, meaning your symptoms have improved by less than 50%. You need to be taking at least the minimum effective dose of one of several specified antidepressants for at least 6 weeks.

Main exclusion criteria: You cannot participate if you have a good response to your current antidepressant therapy, are under 18 or over 65 years old, are pregnant or breastfeeding, have other medical conditions that might interfere with the study, are currently participating in another clinical trial, have a history of substance abuse or dependence within the past year, or have a known allergy or sensitivity to the study medication.

Study focus: The trial lasts for 43 days (about 6 weeks), during which you will take either lumateperone 42 mg or a placebo once daily alongside your ongoing antidepressant therapy. The primary focus is on the change in the Montgomery-Åsberg Depression Rating Scale total score from the baseline to the end of the study. Regular assessments will monitor changes in depression symptoms and overall health.

Investigational drug: Lumateperone is being studied as an additional treatment for Major Depressive Disorder when standard antidepressant therapies haven’t been effective enough. It is taken orally once daily as a capsule and works by modulating neurotransmitter systems in the brain, including serotonin, dopamine, and glutamate.

Study on Minocycline and Celecoxib for Patients with Major Depressive Disorder Not Responding to Antidepressants

This trial is testing whether Minocycline or Celecoxib can help improve symptoms of depression when added to current treatment for people who have not responded to one or two previous antidepressant treatments. The study is being conducted in Belgium.

Main inclusion criteria: You must be between 18 and 65 years old and able to give informed consent and take oral medication. You need to be physically healthy and have a diagnosis of Major Depressive Disorder confirmed by the Mini International Neuropsychiatric Interview. Your current episode of depression must have failed to improve with the current antidepressant treatment at the right dose, or the depression returned while on an antidepressant. You must be stable on your current treatment for at least 4 weeks (or 6 weeks for fluoxetine) before starting the study and have a Hamilton Depression Rating Scale score of 14 or higher.

Main exclusion criteria: You cannot participate if you do not have Major Depressive Disorder, have not tried at least one or two antidepressant treatments without success, are not within the age range specified, or are part of a vulnerable population unable to give informed consent.

Study focus: The trial lasts for 12 weeks, during which you will be randomly assigned to receive either Minocycline (100 mg film-coated tablet), Celecoxib (200 mg hard capsule), or a placebo. You will continue your current treatment while taking the assigned medication. Regular follow-up visits will monitor your progress, and assessments will include depression severity, sleep quality, anxiety levels, and metabolic health indicators. The primary goal is to measure changes in the Hamilton Depression Rating Scale score.

Investigational drugs: Minocycline is an antibiotic being tested for its potential to reduce inflammation in the brain, which might improve symptoms of depression. Celecoxib is a pain and inflammation medication being tested to see if targeting inflammation can help improve depression symptoms in people who haven’t found relief with typical antidepressant medications.

Study on Pramipexole for Reducing Anhedonia in Patients with Major Depression

This trial is investigating whether Pramipexole can reduce anhedonia (difficulty feeling pleasure in activities) in individuals with major depression. The study is taking place in Sweden.

Main inclusion criteria: You must be between 18 and 75 years old and have a diagnosis of unipolar depressive episode, bipolar disorder in depressive phase, or dysthymia (persistent mild depression). You need to be experiencing anhedonia symptoms, measured by scoring 3 or 4 points on at least 3 items of the Snaith-Hamilton Pleasure Scale. You must currently be taking at least one antidepressant or mood stabilizing medication for at least 4 weeks and have tried an antidepressant at a therapeutic dose but not achieved remission (refractory stage 1 depression).

Main exclusion criteria: You cannot participate if you have other serious mental health conditions besides major depression, have had a recent heart attack or have severe heart disease, have uncontrolled high blood pressure, severe liver or kidney disease, are pregnant or breastfeeding, are currently using certain medications that might interfere with the study treatment, have a history of allergic reactions to similar medications, have participated in another clinical trial within the last 30 days, have a history of substance abuse or addiction within the past year, or are unable to comply with study procedures.

Study focus: The trial lasts for nine weeks. You will be randomly assigned to receive either pramipexole or placebo. The maximum dosage of pramipexole will be 3.15 milligrams per day, adjusted to avoid intolerable side effects. Regular assessments will track changes in anhedonia symptoms using questionnaires, and you may also undergo brain imaging to observe brain activity related to pleasure and reward.

Investigational drug: Pramipexole is being studied for its potential to help with symptoms of anhedonia in people with major depression. It works by affecting certain chemicals in the brain linked to mood and motivation, and the study aims to find out if it can help improve feelings of pleasure without causing too many side effects.

Study on Psilocybin for Treating Depression in Cancer Patients

This trial is examining the effects of a single dose of psilocybin for treating Major Depressive Disorder in patients who have been diagnosed with cancer. The study is being conducted in Sweden.

Main inclusion criteria: You must be between 20 and 80 years old and able to read, speak, and understand Swedish. You need to have a diagnosis of a malignant neoplasm (cancer) with at least one month since diagnosis and at least 12 months of life expectancy. Your physical functioning should be at a level of 0 to 2 according to the WHO or ECOG scale. You must meet the criteria for major depressive disorder with a current depressive episode lasting at least 30 days but less than one year, with moderate to severe symptoms shown by a PHQ-9 score. You must be willing to stop other depression treatments during the 180-day study period.

Main exclusion criteria: You cannot participate if you have a current diagnosis of Major Depressive Disorder without cancer, have malignant tumors identified by codes C00 to C97, are not willing to stop other treatments for depression during the study, have been diagnosed with cancer less than one month ago, or do not have at least 12 months of life expectancy.

Study focus: The trial compares a 25 mg dose of psilocybin to a smaller 1 mg dose. You will receive a single oral dose and be monitored for changes in depressive symptoms over time. The primary evaluation occurs at Day 42, with follow-up continuing until Day 180 to monitor long-term effects and any need for additional antidepressant treatment.

Investigational drug: Psilocybin is being studied for its potential to treat major depressive disorder in patients with cancer. It is administered orally, typically in capsule form, and works by interacting with serotonin receptors in the brain, which can lead to changes in mood and perception.

Study on Seltorexant for Adults and Elderly with Major Depressive Disorder and Insomnia Symptoms

This trial is evaluating how well seltorexant works when used alongside other antidepressants (SSRIs or SNRIs) for adults and elderly patients with Major Depressive Disorder who also have trouble sleeping. The study is being conducted in Poland, Romania, Slovakia, Czechia, Portugal, Spain, Bulgaria, Italy, and Sweden.

Main inclusion criteria: You must be between 18 and 74 years old and in good health based on physical examination, vital signs check, and heart test (ECG). You need to have a confirmed diagnosis of Major Depressive Disorder without psychotic features and currently be in a major depressive episode with insomnia symptoms. You should have had an inadequate response to certain antidepressants (SSRIs or SNRIs), and you must be currently taking one of these antidepressants at a stable therapeutic dose for at least 6 weeks. Your depression must be moderate to severe, with a MADRS total score of 25 or higher at both screening and baseline, and the change between these scores must be 20% or less.

Main exclusion criteria: You cannot participate if you have a medical condition other than Major Depressive Disorder with insomnia symptoms, have had an adequate response to your current SSRI/SNRI antidepressant therapy, are not within the specified age range, or are not able to follow study procedures.

Study focus: The trial has two main parts. In Part 1, lasting 43 days, you will receive either seltorexant 20 mg or placebo as an additional treatment to your current antidepressant. The goal is to assess the effectiveness of seltorexant in improving depressive symptoms. If you show a stable response, you may proceed to Part 2, a maintenance phase designed to evaluate whether seltorexant can delay the relapse of depressive symptoms.

Investigational drug: Seltorexant is being studied as an additional treatment for Major Depressive Disorder with insomnia symptoms. It is taken orally in film-coated tablet form alongside existing antidepressant medications. It works by selectively antagonizing the orexin-2 receptor, which is believed to play a role in regulating mood and sleep.

## Summary

These 10 clinical trials represent a diverse range of innovative approaches to treating Major Depressive Disorder. The studies span multiple European countries, with notable concentrations in Belgium (7 trials), several Eastern European nations including Poland, Bulgaria, and Czechia, and Scandinavian countries such as Sweden and Finland.

A significant focus of current research is on adjunctive therapies—treatments added to existing antidepressants for patients who haven’t responded adequately to standard treatment. Several trials are testing NBI-1065845 in various formulations and durations, suggesting considerable interest in this investigational compound. Other novel approaches include the kappa opioid receptor antagonist being studied, anti-inflammatory medications like minocycline and celecoxib, and dopamine agonists such as pramipexole.

The trials also reflect growing interest in psychedelic compounds, with psilocybin being studied in cancer patients with depression. Additionally, several studies are exploring treatments for specific depression subtypes, such as those with anhedonia (inability to feel pleasure) or insomnia symptoms.

Many trials emphasize long-term safety and relapse prevention, recognizing that depression is often a chronic, recurring condition. The geographic diversity of these studies across Europe suggests strong international collaboration in depression research, potentially allowing for more comprehensive understanding of treatment effects across different populations.