AuthorisedTherapeutic use (Phase IV)Interventional

Unprescribing the Pill to Reassess Symptom and Cognitive Recovery in Depression (UNPRESCRIB-D)

Depression is a common condition that can affect your mood, daily energy, and thinking skills such as memory and focus. Many women take the combined contraceptive pill, but scientists still do not fully understand how hormonal contraception might influence depression or recovery. The UNPRESCRIB-D study aims to find out whether stopping the contraceptive pill helps women recover more effectively from depression. Participants will receive antidepressant treatment (such as sertraline or duloxetine) alongside either their usual contraceptive pill or a dummy pill (placebo). Researchers will carefully measure changes in depressive symptoms, memory, and attention. They will also look at biological markers like brain activity, stress hormones, and inflammation. The aim of this research is to give doctors and women clearer evidence about whether stopping the pill could be a helpful step in treating depression.

At a glance

Status

Authorised

Phase

Therapeutic use (Phase IV)

Sponsor

Region Hovedstaden

Enrolment target

106

Start

29 Jun 2026

Major Depressive Disorder

What is this study about?

Depression is more than just feeling low for a few days; it is a serious illness that can cause persistent sadness, exhaustion, and difficulties with memory and problem-solving. While antidepressants can be very effective, not everyone recovers completely, and scientists are keen to find ways to help treatments work better.

Many women take hormonal contraceptives, such as 'the pill', at the same time as antidepressants. Hormones have powerful effects on the body and brain, but it is currently unclear whether taking the pill makes it easier or harder to bounce back from depression. This study was designed to investigate whether 'unprescribing' or pausing the pill can lead to better emotional and mental recovery.

In this trial, women with depression will be offered standard antidepressant medications, including sertraline or duloxetine. At the same time, researchers will compare those who continue taking a contraceptive pill against those who take a placebo (a pill with no active ingredients). This allows researchers to see the true effect of stopping the pill on mood and cognitive function.

By gathering detailed information from memory tests, blood samples, and brain scans, the study team hopes to uncover how hormones interact with brain chemistry and antidepressants. In the long run, this could help doctors provide more personalised, effective treatment plans for women experiencing depression.

Key takeaways

The study explores whether stopping the contraceptive pill improves recovery from depression.
It measures improvements in low mood as well as thinking skills like memory and attention.
Participants receive an antidepressant and either a real contraceptive pill or a dummy pill.
Only adult women aged 18 and over can take part.
Alternative barrier contraception (such as condoms) is required throughout the study.
Participation is completely voluntary, and you can leave at any time.

Who may be eligible?

This clinical trial is designed for adult women who have been diagnosed with major depressive disorder (clinical depression). To take part, you must be aged 18 or older.

Because the study investigates the impact of hormonal birth control, it is aimed at women who are currently using or eligible to take the combined oral contraceptive pill, and who may benefit from starting or adjusting antidepressant treatment such as sertraline or duloxetine.

You may not be eligible if you have certain other medical conditions, are pregnant or planning a pregnancy, or cannot safely take the medications or undergo brain scans used in the study. A member of the research team will carry out a thorough health review to see if the study is safe and suitable for you.

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.

I am a woman aged 18 or older.
I am currently experiencing symptoms of depression or have a diagnosis of major depressive disorder.
I am currently taking, or able to take, the combined contraceptive pill.
I am willing and able to take standard antidepressant tablets (sertraline or duloxetine).
I am not currently pregnant and agree to use non-hormonal contraception during the trial.

Answer every question to see your result.

What does participation involve?

If you decide to take part, you will be assigned to take an antidepressant (such as sertraline or duloxetine) alongside either an active contraceptive pill or an inactive dummy pill (placebo). You will be asked to attend regular clinic visits over several weeks or months so the medical team can monitor your health and mood. During these visits, you will complete memory and concentration exercises, answer questionnaires about your emotions, and provide blood samples to check hormone levels and inflammation. Some participants may also be invited to have specialised, non-invasive brain scans (such as MRI or PET scans) to see how the brain responds to treatment. The study team will explain the exact schedule and duration before you agree to join.

Potential risks and benefits

Taking part offers the benefit of frequent, comprehensive health checks and close support from a specialist medical team, while also helping improve depression treatments for other women in the future. However, there are potential risks and inconveniences. Common antidepressants and changes to hormonal contraception can cause side effects like temporary nausea, headaches, sleep changes, or changes in menstrual bleeding. If you switch to a dummy pill, you will also need to use non-hormonal contraception (like condoms) to prevent unplanned pregnancy. Joining is entirely voluntary, and you can change your mind and leave the study at any time without your regular NHS care being affected in any way.

Locations (1)

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

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Unverified
Denmark

Common questions

Will I definitely receive an active antidepressant?

Yes, all participants in this trial receive standard antidepressant medication to treat their depression, whilst the contraceptive pill part of the trial may involve an active pill or a dummy pill.

Could I become pregnant during this study?

Because some participants may receive an inactive dummy pill instead of a real contraceptive pill, you must use reliable, non-hormonal barrier contraception (such as condoms) to avoid pregnancy during the study.

What will happen during the memory tests?

The memory tasks are simple, non-invasive exercises. You may be asked to remember lists of words, solve short puzzles, or complete computer-based games to check your focus, learning, and recall.

Do I have to pay to take part?

No, you do not have to pay for any study medications, tests, or appointments. Some studies also help cover reasonable travel expenses to and from the clinic.

What if my depression gets worse during the trial?

Your safety is the top priority. The study team will monitor your symptoms very closely at every visit, and if your mood worsens, your doctor can adjust your care or withdraw you from the trial immediately.