RecruitingPhase IIIInterventional

Assessing the effectiveness of lithium plus quetiapine compared to lithium alone or quetiapine alone for treatment of adults with bipolar disorder

This UK-based study, called COMBINER, investigates the most effective long-term treatment for adults with bipolar disorder. It compares taking lithium, quetiapine, or both together, to stop periods of severe depression or feeling overly elated (mania or hypomania). Researchers know both medications help, but they want to know if combining them is better. The study aims to recruit around 300 adults with bipolar disorder to take one of these treatments for up to two years. Participants will have regular check-ups to see which treatment works best, how acceptable it is, and its impact on quality of life. The study will also look at how cost-effective each approach is.

At a glance

Status

Recruiting

Phase

Phase III

Sponsor

University of Birmingham

Enrolment target

303

Start

20 May 2025

Estimated completion

31 Jul 2027

Bipolar disorder

What is this study about?

If you live with bipolar disorder, you'll know how important it is to find a treatment that helps you live a stable and fulfilling life. This study, called COMBINER, is looking into how well two commonly prescribed medications for bipolar disorder – lithium and quetiapine – work over the long term. These medications are often used as 'maintenance treatments', which means they're taken regularly to reduce the chances of experiencing mood swings, like severe depression or feeling overly high (mania or hypomania).

Doctors already know that both lithium and quetiapine can be effective on their own. However, what they don't fully understand is whether taking them together might be even better at preventing mood episodes, or if one is clearly superior to the other. The COMBINER trial aims to answer these vital questions, helping to improve future treatment guidelines and ensure people with bipolar disorder receive the most effective care.

The study will follow participants for up to two years, closely monitoring their mood, any side effects they experience, and how the treatment affects their daily lives and overall well-being. This will help researchers not only see which treatment is most effective at preventing mood episodes but also which is most acceptable and improves quality of life. The findings will be really important for doctors and patients deciding on the best long-term treatment plans.

Key takeaways

Compares lithium, quetiapine, or both for long-term bipolar disorder treatment.
Aims to find the most effective maintenance strategy for adults.
Participation involves taking medication for up to two years with remote check-ups.
Focuses on preventing mood swings and improving quality of life.
Recruitment starts May 2025, funded by NIHR (UK).
Contributions will help shape future bipolar disorder treatment.

Who may be eligible?

This study is open to adults aged 18 or over who have been diagnosed with bipolar disorder type 1 or 2. It’s important that you are not currently in a mood episode (like severe depression, mania, or hypomania) when you join.

You might be able to take part even if you are already on lithium or quetiapine, as long as you and your doctor are open to possibly changing your treatment as part of the study. You also need to be able to understand and agree to take part in the study.

There are some reasons you wouldn't be able to join. For example, if you have another main diagnosis like substance dependence, if your doctor thinks you are at immediate risk of self-harm, or if you have serious untreated health problems. Also, if you have certain kidney problems (eGFR below 60), specific heart conditions, untreated thyroid issues, or other medical issues where lithium or quetiapine might be risky, you wouldn't be eligible. Women who could become pregnant must not be pregnant and must be willing to use effective contraception throughout the study.

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 18 years old or older?
Have you been diagnosed with bipolar disorder (type 1 or 2)?
Are you currently stable, meaning you're not in a severe mood episode (like depression or mania)?
Are you willing to potentially change or start a new bipolar medication as part of the study?
Do you have good kidney function (eGFR 60 or higher)?
If you could become pregnant, are you willing to use effective contraception during the study?

Answer every question to see your result.

What does participation involve?

If you decide to take part in the COMBINER study, you would be one of about 300 people randomly chosen to receive one of three treatment options: lithium only, quetiapine only, or both medications together. You would take this assigned treatment for up to two years.

The study would involve regular check-ups. You'd have more detailed and longer appointments when you first join, at one year, and at two years. In between, you'd have shorter, remote follow-up visits every three months for 24 months. During these visits, researchers will ask about your mood, any side effects, your general well-being, and how the treatment is fitting into your life. The whole study, from start to finish, is expected to run for 68 months, with recruitment of participants beginning in May 2025.

Potential risks and benefits

The study aims to find the best way to manage bipolar disorder for the long term. While specifics weren't provided at the time of registration, potential benefits of taking part could include receiving regular medical support and monitoring, and contributing to important research that will help many others with bipolar disorder in the future. As with any medication, there are potential side effects associated with lithium and quetiapine, which your study team would discuss in detail. You would have the right to withdraw from the study at any time, for any reason, without it affecting your usual medical care.

Locations (1)

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

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Unverified
United Kingdom

Common questions

What is the main goal of the COMBINER study?

The main goal is to find out if taking lithium and quetiapine together is better than taking either one alone for preventing mood swings in adults with bipolar disorder.

How long will I need to be in the study if I participate?

If you take part, you will be followed for up to two years, taking the assigned study medication during this time.

Will I know which treatment I'm getting?

You will be told whether you are taking lithium, quetiapine, or both, as you will be randomly assigned to one of these groups.

Who is funding this research?

The study is funded by the National Institute for Health and Care Research (NIHR) in the UK.

What if I'm already taking one of these medications?

You may still be able to join if you and your doctor are willing to consider changing or adjusting your treatment as part of the study.

How to find out more

Samantha Hopkins

combiner@trials.bham.ac.uk - Official trial record

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