A proof-of-concept study of an accessible lithium supplement
| ISRCTN | ISRCTN12858621 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12858621 |
| Integrated Research Application System (IRAS) | 329291 |
| Sponsor | Institute of Psychiatry, Psychology & Neuroscience and South London & Maudsley NHS Foundation Trust joint office |
| Funder | Psychiatry Research Trust |
- Submission date
- 25/07/2024
- Registration date
- 01/08/2024
- Last edited
- 21/04/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims:
Lithium is the gold-standard medication for bipolar depression and mania, and is also effective in unipolar depression, but is under-used because it requires frequent blood tests to ensure safety for patients. 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, anxiety and agitation, all particularly relevant for depression. 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 depression 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 depression.
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. People also have to be suitable and willing to try supplementary lithium and visit our research centre for measures 5 times over 6 months (as below).
What does the study involve?
Participants will be asked to visit our research centre 5 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, 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 2027
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
Contact information
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 |
| becci.strawbridge@kcl.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Open label single arm proof of concept study |
| Secondary study design | Non randomised study |
| Participant information sheet | ISRCTN12858621 PIS MixLi_329291_v1.1_18092024.pdf |
| Scientific title | Lithium orotate: a potential accessible supplement for people experiencing depression |
| Study acronym | MixLi |
| Study objectives | To establish initial feasibility of studying a commercially available supplement (lithium orotate; LiOr) for its potential mood effects in people with depression including mixed features (DMF). |
| Ethics approval(s) |
Approved 08/10/2024, Westminster Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 1048146; westminster.rec@hra.nhs.uk), ref: 24/LO/0620 |
| Health condition(s) or problem(s) studied | People experiencing an episode of depression |
| Intervention | A lithium supplement which is currently available to purchase worldwide over the counter. Formulation: Lithium orotate Dose: up to 20 mg per day Duration: Up to 6 months |
| Intervention type | Supplement |
| Primary outcome measure(s) |
Current primary outcome(s) as of 21/04/2026: |
| Key secondary outcome measure(s) |
Current key secondary outcome(s) as of 21/04/2026: |
| Completion date | 31/01/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | All |
| Target sample size at registration | 40 |
| Key inclusion criteria | Current key inclusion criteria as of 21/04/2026: 1. Aged between 18 - 65 years at study entry 2. Meet DSM-5 criteria for a current depressive episode (MINI) 3. Undergoing stable pharmacological treatment for depression (intervention/dose unchanged for >6 weeks) 4. Willing to try a commercially available lithium supplement 5. Willing to attend planned study visits _____ Previous key inclusion criteria: 1. Aged between 18 - 65 years at study entry 2. Meet DSM-5 criteria for a current depressive episode (MINI) and exceed thresholds indicating presence of mixed features (Internal States Scale; ISS) 3. Undergoing stable pharmacological treatment for depression (intervention/dose unchanged for >6 weeks) 4. Willing to try a commercially available lithium supplement 5. Willing to attend planned study visits |
| Key exclusion criteria | 1. Clinical diagnosis of bipolar disorder. 2. Other health condition that is severely impairing 3. Known contraindication to lithium treatment. This includes currently taking lithium 4. Unable to communicate fluently in English 5. Suicide risk |
| Date of first enrolment | 28/10/2024 |
| Date of final enrolment | 30/06/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Monks Orchard Road
Beckenham
BR3 3BX
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Rebecca Strawbridge, becci.strawbridge@kcl.ac.uk, with the type of (anonymised) data depending on the request, available from 26 weeks after data collection has been completed, subject to participants’ consent. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.1 | 18/09/2024 | 09/10/2024 | No | Yes |
| Participant information sheet | version 5 | 18/03/2026 | 21/04/2026 | No | Yes |
| Protocol file | version 1.2 | 08/10/2024 | 09/10/2024 | No | No |
| Protocol file | version 7 | 16/02/2026 | 21/04/2026 | No | No |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- ISRCTN12858621 PIS MixLi_329291_v1.1_18092024.pdf
- Participant information sheet
- ISRCTN12858621 Protocol MixLi_329291_v1.2_08102024.pdf
- Protocol file
- ISRCTN12858621 ProtocolMixLi_329291_v7_16.02.2026.pdf
- Protocol file
- ISRCTN12858621 PIS MixLi_329291_v5_18.03.26.pdf
- Participant information sheet
Editorial Notes
21/04/2026: The following changes were made to the study record:
1. Uploaded protocol v7.0 (not peer-reviewed) as an additional file.
2. The participant information sheet v5.0 was uploaded as an additional file.
3. The plain English summary was updated.
4. The scientific title was changed from "Lithium orotate: a potential accessible supplement for people experiencing depression with mixed features" to "Lithium orotate: a potential accessible supplement for people experiencing depression".
5. The primary outcome(s) were changed.
6. The key secondary outcome(s) were changed.
7. The key inclusion criteria were changed.
30/12/2025: The following changes were made to the study record:
1. The date of final enrolment was changed from 30/11/2025 to 30/06/2026.
2. The completion date was changed from 31/01/2026 to 31/01/2027.
04/07/2025: The date of final enrolment was changed from 31/07/2025 to 30/11/2025.
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.
