Not yet recruitingNAINTERVENTIONAL

Using Fenfluramine to Test the Serotonin Deficiency Theory of Depression

This study is investigating a long-standing idea that depression might be caused by not having enough of a brain chemical called serotonin. Many common antidepressant medicines, like SSRIs, work by targeting serotonin. The researchers want to directly see if serotonin levels are different in the brains of people with depression. They will use a special scanning technique called PET, combined with a medicine called Fenfluramine, which briefly increases serotonin. This will help them compare how serotonin is released in people with depression versus healthy volunteers. The aim is to get a clearer picture of how serotonin might be involved in depression and to potentially find ways to predict who might benefit most from existing treatments.

At a glance

Status

Not yet recruiting

Phase

Sponsor

Imperial College Healthcare NHS Trust

Enrolment target

Start

01 Jul 2026

Estimated completion

01 Dec 2028

Depression - Major Depressive Disorder

What is this study about?

Depression is a common illness that can make people feel sad, lose interest in things they enjoy, and find it hard to manage their daily life. For a long time, doctors and scientists have thought that problems with a brain chemical called serotonin might play a big role in depression. This idea is known as the 'serotonin deficiency hypothesis,' and it's why many common antidepressant medicines, called SSRIs, work by affecting serotonin levels in the brain.

However, it's been difficult to directly check if serotonin levels are actually lower or less active in the brains of people with depression. This study aims to do just that, using advanced scanning technology. Researchers will use a special type of scan called a PET scan, along with a mild medicine called Fenfluramine. Fenfluramine temporarily releases serotonin in the brain. By observing how a special dye (called [11C]Cimbi-36) binds in the brain before and after Fenfluramine, researchers can get a clearer idea of how much serotonin is being released. They will compare these findings in people with depression and healthy volunteers.

Ultimately, this study hopes to provide solid evidence about whether serotonin problems are directly linked to depression. This understanding could lead to more effective and personalised ways to treat depression in the future, helping doctors better understand why some people respond well to certain antidepressants and others don't.

Key takeaways

The study explores if low serotonin causes depression.
It uses special brain scans with a temporary serotonin-boosting medicine.
Compares people with depression to healthy volunteers.
Aims to improve treatments by understanding serotonin's role.
Participants with depression on SSRIs will be followed up.
Your participation could advance understanding of depression.

Who may be eligible?

To join this study, everyone must be at least 21 years old and be able to lie comfortably on their back for the scans. You'll need to be able to understand and sign consent forms, and be able to read and record information in English. You also need access to the internet on your own device.

If you have depression, you must have been diagnosed with moderate to severe major depressive disorder and score above 20 on a specific depression scale (MADRS). You either can't have taken antidepressants before, or you must have stopped taking them at least 8 weeks before agreeing to join the study. You also shouldn't have depression that is considered 'treatment-resistant' and need to be seeing a GP or other healthcare professional regularly.

If you're a healthy volunteer, a doctor will need to confirm you are healthy based on a medical check-up, including your medical history, a physical exam, and blood tests. Everyone will be checked to make sure they don’t have any other serious medical or mental health conditions (apart from depression for the patient group) that could make taking part unsafe or affect the study's results. You also can't be taking certain medications that might interfere with the study's findings, or have used illegal drugs in the last 3 months.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you 21 years old or older?
Can you lie comfortably for a scan?
Are you able to read and understand information in English?
If you have depression: Have you been diagnosed with moderate to severe depression (and meet specific score criteria)?
If you have depression: Have you never taken antidepressants, or stopped them at least 8 weeks ago?
If you are a healthy volunteer: Are you generally healthy with no major medical or mental health conditions?

Answer every question to see your result.

What does participation involve?

If you decide to take part, you will have several visits to the study centre. For the main part of the study, you'll undergo special brain scans called PET scans. Before these scans, you'll receive a small amount of a medicine called Fenfluramine, which helps measure serotonin release in your brain. You will also have blood tests and fill out questionnaires about your mood and feelings.

If you have depression and are planning to start SSRI antidepressant treatment as part of your usual care, the study team will follow up with you after your scans for 8 weeks. During this follow-up period, you'll complete assessments remotely (from home) to see how your mood changes with treatment. The total duration of your involvement will depend on whether you are in the depression group and undergo the follow-up, but generally will involve a few initial visits and then remote check-ins for the depression group.

Potential risks and benefits

Taking part in this study may help scientists understand depression better, potentially leading to new treatments in the future. For those with depression who are starting SSRIs, the study aims to understand what predicts a good response to treatment. While the medicines and scans used are generally safe, there are some potential risks associated with Fenfluramine, such as temporary changes in heart rate or blood pressure, and a very small risk from the radiation in the PET scans. You will be closely monitored by medical staff throughout the study, and you have the right to withdraw from the study at any time without giving a reason, and this will not affect your usual medical care.

Locations (1)

entre for Psychedelics Research, Division of Psychiatry Imperial College London, Level 2, Commonwealth Building, Hammersmith Campus, Du Cane Road, London
Verified postcode
London, United Kingdom

Common questions

What is serotonin and why is it important?

Serotonin is a natural chemical in your brain that helps control your mood, sleep, appetite, and other important functions. Many scientists believe that an imbalance of serotonin might contribute to depression.

What is a PET scan?

A PET scan is a special type of imaging test that allows doctors to see how your organs and tissues are working. In this study, it's used to look at serotonin activity in your brain.

Will I receive treatment for my depression in this study?

This study itself isn't a treatment program. If you have depression and plan to start SSRI treatment as part of your regular care, the study will follow your progress to understand how you respond to this treatment.

What is Fenfluramine?

Fenfluramine is a medication that briefly increases the amount of serotonin in your brain. In this study, it helps researchers measure how your brain reacts to increased serotonin.

Will I know my personal study results?

The study aims to understand group differences, and individual results are part of larger research data. Specific personal results may not be shared, but aggregated findings will contribute to scientific understanding.

How to find out more

David Erritzoe, MD., PhD.

d.erritzoe@imperial.ac.uk +447503289090 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.