Condition category
Mental and Behavioural Disorders
Date applied
29/08/2006
Date assigned
30/08/2006
Last edited
07/06/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
One in five people experience depression during their lives. Only half of those treated with drugs will get better; many others experience symptoms for a long time. The most common type of treatment for depression is a drug known as an antidepressant. These work by improving the way in which certain chemical messengers work in the brain. The vitamin called folate, found in foods such as green vegetables, helps to produce the chemicals used by these messengers in the brain. So low levels of folate, caused by poor diet or similar factors, may worsen or even cause depression, and may stop antidepressants from working as well as they should. This means that taking folate tablets could help treat depression. However, very few studies have been done to test this. This study will test whether giving a tablet of folate every day to people with depression will help their antidepressants work better.

Who can participate?
Patients aged 18 or over with moderate to severe depression

What does the study involve?
Participants are randomly allocated to take either a folate tablet or a dummy tablet for 3 months in addition to their antidepressant. To test whether folate tablets help antidepressants to work better, we assess whether those taking the tablets achieve better health. To do this we measure peoples' symptoms of depression at different times during the study. We also check their blood to see how much folate they have at different times during the study. We shall use some of the blood samples to see whether any genes affect the way folate helps treat depression.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
University of Wales Bangor (UK)

When is the study starting and how long is it expected to run for?
October 2006 to June 2011

Who is funding the study?
Health Technology Assessment Programme (UK)

Who is the main contact?
Prof. Ian Russell
ian.russell@bangor.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Ian Russell

ORCID ID

Contact details

IMSCaR
Brigantia Building
Penrallt Road
Bangor
LL57 2AS
United Kingdom
+44 (0)1248 383617
ian.russell@bangor.ac.uk

Additional identifiers

EudraCT number

2006-004647-37

ClinicalTrials.gov number

NCT00514410

Protocol/serial number

HTA 04/35/08

Study information

Scientific title

Folate Augmentation of Treatment - Evaluation for Depression: a randomised controlled trial

Acronym

FolATED

Study hypothesis

The primary objective of this trial is to estimate the effect of folate augmentation in new or continuing treatment of depressive disorder in primary, intermediate and secondary care. Secondary objectives are to evaluate the cost-effectiveness of folate augmentation of antidepressant treatment, investigate how the response to antidepressant treatment depends on genetic polymorphisms relevant to folate metabolism and antidepressant response, and explore whether baseline folate status can predict response to antidepressant treatment.

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/043508
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0003/51078/PRO-04-35-08.pdf

Ethics approval

MREC for Wales, 06/11/2006, CTA ref: 21996/0001/001-0001

Study design

Multi-centred double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Moderate to severe depression

Intervention

Folic acid 5 mg versus placebo supplementation to antidepressant therapy.

Intervention type

Supplement

Phase

Drug names

Primary outcome measures

Symptom severity as estimated by the self-rated Beck Depression Inventory (BDI)

Secondary outcome measures

1. Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS)
2. Clinical Global Impression (CGI) of change
3. SF-12 short form health survey
4. Adverse events and side effects as measured by the UKU side effect scale
5. EuroQoL (EQ-5D)
6. Health Resource Use questionnaire

Overall trial start date

01/10/2006

Overall trial end date

30/06/2011

Reason abandoned

Eligibility

Participant inclusion criteria

Only patients aged 18 or over with an International Classification of Diseases (ICD-10) diagnosis of moderate to severe depression (confirmed by the trial psychiatrists during the screening interview using Beck Depression Inventory [BDI]) will be included. Only patients able to give informed consent (not delirious, actively psychotic or with severe communication or learning disability) and able to complete the research assessments will be included.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

730

Participant exclusion criteria

1. Patients that are folate deficient (provisionally set at less than 2.5 ng/l): they cannot be randomised because they need to be treated with folic acid but can be included in the comprehensive cohort
2. Are B12 deficient (provisionally set at less than 150 pg/ml): they cannot be randomised because they need to be treated with B12 injections but can be included in the comprehensive cohort
3. Have knowingly taken supplements containing folic acid within two months because this will mask any effects of folic acid given during the study
4. Substance misuse because people who use drug and alcohol typically have low folate levels
5. Suffer from psychosis because additional treatment for psychosis may mask any benefit of folic acid with antidepressants. Plus people suffering from psychosis are less able to give informed consent and will require referral through to secondary services
6. Are already participating in another research project
7. Are pregnant or planning to become pregnant as it is important for pregnant women to take folic acid so they cannot be randomised to placebo
8. Are taking anticonvulsants as in very rare circumstances folic acid can react with certain anticonvulsants
9. Serious, advanced or terminal illness with a life expectancy of less than one year
10. Have recently started treatment for a medical condition which has not yet been stabilised

Recruitment start date

01/10/2006

Recruitment end date

30/06/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

IMSCaR
Bangor
LL57 2AS
United Kingdom

Sponsor information

Organisation

University of Wales Bangor (UK)

Sponsor details

Brigantia Building
Penrallt Road
Bangor
LL57 2AS
United Kingdom
+44 (0)1248 383617
ian.russell@bangor.ac.uk

Sponsor type

University/education

Website

http://www.bangor.ac.uk/index.php.en?width=1024&height=768

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2007 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/18005429
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25052890

Publication citations

  1. Protocol

    Roberts SH, Bedson E, Hughes D, Lloyd K, Menkes DB, Moat S, Pirmohamed M, Slegg G, Thome J, Tranter R, Whitaker R, Wilkinson C, Russell I, Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial., BMC Psychiatry, 2007, 7, 65, doi: 10.1186/1471-244X-7-65.

  2. Results

    Bedson E, Bell D, Carr D, Carter B, Hughes D, Jorgensen A, Lewis H, Lloyd K, McCaddon A, Moat S, Pink J, Pirmohamed M, Roberts S, Russell I, Sylvestre Y, Tranter R, Whitaker R, Wilkinson C, Williams N, Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised trial and economic evaluation, Health Technol Assess, 2014 , 18, 48, 1-159, doi: 10.3310/hta18480.

Additional files

Editorial Notes

07/06/2016: Plain English summary added. 26/08/2009: the overall trial end date of this trial was changed from 30/06/2009 to 30/06/2011.