A proof-of-concept study of an accessible lithium supplement

Plain English Summary

Background and study aims:
Depression with mixed features (DMF) is where people experiencing a depressive episode also have symptoms of mania at the same time (for example, agitation, racing thoughts, reduced inhibition). DMF is common, occurring in up to a quarter of people with depression, and is associated with greater disability compared to depression without mixed features. DMF is particularly common in people with bipolar (spectrum) illnesses, and in people without a bipolar diagnosis is a significant risk factor for later receiving a bipolar diagnosis. The difficulties in treating DMF are well documented, and these challenges are compounded by the fact that DMF is often undetected in healthcare services and therefore not treated. (Full-dose) lithium is the gold standard medication for bipolar depression and mania, but is under-used because it requires frequent blood tests to ensure safety for patients. Our work, though, shows benefits of lower doses of lithium for depression and mania (when used alongside other medications) as well as cognitive function (e.g., memory). Because DMF includes symptoms of mania and depression (plus often cognitive difficulties), lower doses of lithium could be an effective add-on treatment. Mixed features are often not recognised in healthcare services, which reduces the potential for prescribed lithium. However, non-medication forms of lithium are available at a low dose (20mg) over-the-counter as a ‘nutraceutical’ (“LiOr”) and could be accessible for many people to take, if found to be effective. My previous research shows that low-dose lithium is safe, and that – anecdotally – people find it helpful for low/fluctuating mood, cognition and agitation, all particularly relevant for DMF. However, LiOr’s potential has not been explored in any reasonable-quality human studies.
This project will provide a ‘proof of concept’ to see whether LiOr could be assessed as a potential therapy at a large scale. We will recruit 40 people with DMF who are under stable ongoing treatment for depression, and measure 1) whether they agree to take 20mg LiOr daily, and how long they take it over a period of up to 6 months, 2) their levels of lithium in the blood, 3) any positive changes (e.g., to mood) over the 6-month study, 3) any negative effects or difficulties participants experience, 4) whether the measures and visits participants are asked to complete are acceptable for people. The results will give us enough information to plan a clinical trial, where LiOr can be robustly compared with a placebo to help determine whether LiOr could have benefits for people with DMF.

Who can participate?
We are looking for people aged 18 - 65 years, who are fluent in English, who do not have a diagnosis of bipolar disorder or are currently very suicidal but are having treatment for depression and have certain symptoms with their depression ('DMF'). People also have to be suitable and willing to try supplementary lithium and visit our research centre for measures 6 times over 6 months (as below).

What does the study involve?
Participants will be asked to visit our research centre 6 times over 6 months for a blood test and some questionnaires. Between visits they will be asked to take LiOr each day, so long as they are willing to do so during this time. After the first visit, we ask that the following visits are 2 weeks, 1 month, 2 months, 4 months and 6 months after the first visit.

What are the possible benefits and risks of participating?
We do not expect any significant risks or negative effects from taking part in the study. It is possible that people may feel some distress during blood tests or some of the questionnaires in visits. It is possible that people may not get on well with the lithium supplement, in which case they can lower the dose or stop taking it. On the other hand, we hope people will find benefits to mood and/or thinking skills and possibly other areas of life from the lithium supplement. Some people find the questionnaire visits interesting. Whether people experience benefits or not, findings from this study may help people in the future, as supplementary lithium is being tested to see if it is helpful for people experiencing a range of mood and brain conditions.

Where is the study run from?
South London and Maudsley NHS Foundation Trust (UK)

When is the study starting and how long is it expecting to run for?
July 2024 to January 2026

Who is funding the study?
Psychiatry Research Trust (UK)

Who is the main contact?
The study team's email address is lithium@kcl.ac.uk.
The lead researcher is Dr Rebecca Strawbridge, becci.strawbridge@kcl.ac.uk

Study website

Contact information

Dr Rebecca Strawbridge
Public, Scientific, Principal Investigator

PO74 Centre for Affective Disorders
103 Denmark Hill
London
SE5 8AZ
United Kingdom

ORCID ID	0000-0002-2984-1124
Phone	+44 2078480088
Email	becci.strawbridge@kcl.ac.uk

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centre

Sponsor information

Funders

Funder type

Charity

Results and Publications

Study outputs

Additional files

ISRCTN12858621 PIS MixLi_329291_v1.1_18092024.pdf

ISRCTN12858621 Protocol MixLi_329291_v1.2_08102024.pdf

Editorial Notes

09/10/2024: The following changes were made to the trial record:
1. The ethics approval was added.
2. The participant information sheet was uploaded as an additional file.
3. Uploaded protocol (not peer-reviewed) as an additional file.
4. The recruitment start date was changed from 01/10/2024 to 28/10/2024.
5. The participant level data sharing statement was added.
6. The study website was added.
25/07/2024: Trial's existence confirmed by Psychiatry Research Trust.