RecruitingInterventional

Serotonin effects on brain function and their relationship to relapse when stopping antidepressants

If you've recovered from depression but are still taking antidepressants and thinking about stopping, this study might be for you. Many people find their depression returns after stopping medication, and this study aims to understand why and who might be at risk. Researchers at University College London will use brain scans and a special protein drink that temporarily lowers a brain chemical called serotonin. This helps them see what happens in the brain when antidepressants are stopped. Participants will have their brain activity measured before stopping their medication and will then be monitored for six months. The goal is to better understand how serotonin and brain function are linked to depression coming back.

At a glance

Status

Recruiting

Sponsor

University College London

Enrolment target

Start

13 Apr 2026

Estimated completion

12 Apr 2028

Depression

What is this study about?

When people have successfully treated their depression with medication and feel well again, they often want to stop taking their antidepressants. However, for some, depression can unfortunately return. Doctors and scientists don't yet fully understand why this happens or how to predict who might experience a relapse after stopping medication. This study aims to shed light on these important questions.

Researchers at University College London want to learn more about how stopping antidepressants affects the brain and its chemistry. They're particularly interested in a brain chemical called serotonin, which antidepressants often target. Participants will undergo a special drink that temporarily lowers serotonin levels in the brain – similar to what might happen when medication is stopped. At the same time, brain activity will be measured using a safe and harmless scanning method. By doing this before someone stops their actual medication, the researchers hope to see early changes that could be linked to future relapse.

The study will follow participants for six months after they stop their antidepressants, carefully monitoring their mood. By comparing the brain measurements and serotonin changes with whether someone's depression returns, the researchers hope to find clues. Ultimately, they aim to discover what makes depression come back after stopping medication, and how serotonin plays a role. This knowledge could lead to better ways to help people stop antidepressants safely in the future.

Key takeaways

Researchers want to understand why depression can return after stopping antidepressants.
The study looks at how brain chemistry, specifically serotonin, is involved.
Participants will have brain scans and a special drink to temporarily lower serotonin.
You'll be monitored for six months after stopping your antidepressant medication.
The findings could lead to better ways to help people safely stop antidepressants.

Who may be eligible?

This study is looking for adults who are between 18 and 64 years old. You should have experienced depression in the past, but now be feeling well and taking antidepressant medication. It's important that you've been feeling stable for at least six weeks and are planning to stop your antidepressant medication.

There are certain reasons why you might not be able to join the study. For example, if you are currently feeling depressed, have a history of bipolar disorder or other serious mental health conditions, or are pregnant or planning to become pregnant soon. Also, if you have certain medical conditions like epilepsy or insulin-dependent diabetes, or if you have metal implants in your head or upper body (like some piercings or dental braces), you likely won't be able to participate due to the brain scanning equipment used.

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 between 18 and 64 years old?
Have you had depression in the past, but are currently feeling well?
Are you currently taking antidepressant medication and want to stop it?
Have you been feeling stable (not depressed) for at least the past six weeks?
Do you not have certain health conditions like epilepsy or bipolar disorder?
Do you not have metal implants in your head or upper body (e.g., some piercings, dental wires)?

Answer every question to see your result.

What does participation involve?

If you decide to take part, you'll visit University College London for some appointments. During these visits, you'll have brain scans using a method called MEG, which is safe and doesn't involve radiation. You'll also be given a special protein drink, designed to temporarily lower one of your brain chemicals called serotonin. After these initial visits, you will then stop taking your antidepressant medication, with support from the study team.

After stopping your medication, you'll continue to do computer tasks at home and the study team will regularly check in with you through phone or video calls for six months to see how you're doing. The entire study involves initial tests, stopping medication, and then six months of follow-up.

Potential risks and benefits

By taking part, your depression will be carefully monitored as you stop your medication. This means if your depression were to return, the team could help you restart treatment quickly. Your contribution could also help improve future treatments for depression for many other people. However, temporarily lowering serotonin may sometimes bring back or worsen depressive symptoms, including very rarely, suicidal thoughts. You might also experience mild side effects like nausea or headaches. These are usually temporary and the team can help manage them. You can also stop participating at any time if you change your mind.

Locations (1)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

University College London Division of Psychiatry and Queen Square Institute of Neurology
Unverified
London, England

Common questions

What is the main goal of this study?

The main goal is to understand why depression sometimes returns after people stop taking antidepressants, and how brain chemistry changes play a role.

What is 'acute tryptophan depletion'?

It's a process where you drink a special protein drink that temporarily lowers levels of a brain chemical called serotonin. It helps researchers understand how the brain responds when serotonin changes.

Will I stop my antidepressant medication as part of the study?

Yes, if you meet the study criteria and agree to participate, you will stop your antidepressant medication as part of the study plan, with monitoring from the study team.

What kind of brain measurements will be taken?

The study uses a safe brain scanning method called magnetoencephalography (MEG), which measures brain activity without any radiation.

Who is funding this research?

This study is funded by the Wellcome Trust, a health research charity in the UK.

How to find out more

Michaela Poppe

m.poppe@ucl.ac.uk +44 (0)20 7679 9311 Official trial record

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