Folate Augmentation of Treatment - Evaluation for Depression: a Randomised Controlled Trial

Depression Clinical Trial

— FolATED  

Official title:

Folate Augmentation of Treatment - Evaluation for Depression: a Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00514410
• Other study ID #: G0373
• Secondary ID: ISRCTN37558856
• Status: Completed
• Phase: Phase 4
• First received: August 9, 2007
• Last updated: October 11, 2011
• Start date: July 2007
• Est. completion date: May 2011

Study information

• Verified date: February 2009
• Source: Bangor University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

To determine whether giving folic acid to people with depression will help their antidepressants work better. If folate does help antidepressants to work better, then it will provide a safe, simple and cheap way of improving the treatment of depression.

Description:

Clinical depression is common, debilitating and treatable; one in four people experience it during their lives. The majority of sufferers are treated in primary care and only half respond well to active treatment. Evidence suggests that folate may be a useful adjunct to antidepressant treatment: 1) patients with depression often have a functional folate deficiency; 2) the severity of such deficiency, indicated by elevated homocysteine, correlates with depression severity, 3) low folate is associated with poor antidepressant response, and 4) folate is required for the synthesis of neurotransmitters implicated in the pathogenesis and treatment of depression.

The primary objective of this multi-centred placebo-controlled randomised trial is to estimate the effect of folate augmentation in new or continuing treatment of depressive disorder in primary 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.

Comparisons: Eligible patients with moderate to severe depression will be randomised to receive 5mg of folic acid or placebo as an adjunct to their antidepressant treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 730
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Only patients aged 18 or over

• ICD-10 diagnosis of moderate to severe depression

• Able to give informed consent (not delirious, actively psychotic or with severe communication or learning disability)

• Able to complete the research assessments

Exclusion Criteria:

• are folate deficient

• are B12 deficient

• have knowingly taken supplements containing folic acid within 2 months

• suffer from psychosis

• are already participating in another research project

• are pregnant or planning to become pregnant

• are taking anticonvulsants

• have a serious, advanced or terminal illness with a life expectancy of less than 1 year

• have recently started treatment for a medical condition which has not yet been stabilised

• are taking lithium

• have had a diagnosis or treatment for any malignant disease or any related condition such as intestinal polyposis

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Drug:
• Folic Acid
Folic acid 5 mg once a day for three months as a supplement to their antidepressant treatment
• Placebo
Matching placebo taken once a day for three months

Locations

Country	Name	City	State
United Kingdom	North West Wales Trust	Bangor	Gwynedd
United Kingdom	Swansea University	Swansea
United Kingdom	Cardiff University	Wrexham

Sponsors (8)

Lead Sponsor	Collaborator
Bangor University	Cardiff University, NHS Health Technology Assessment Programme, North East Wales NHS Trust, North West Wales NHS Trust, Swansea NHS Trust, Swansea University, University of Liverpool

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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 Nov 15;7:65. Erratum in: BMC Psychiatry. 2009;9. doi: 10.1186/1471-244X-9-14. Menkes, David B [added]; Thome, Johannes [added]. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Self rated symptoms of depression using the Beck Depression Inventory		Repeated measures up to 6 months after initiation of folic acid/placebo	No
Secondary	Clinician rated depression using the Montgomery-Asberg Depression Rating Scale		Repeated measures up to 6 months after initiation of folic acid/placebo	No
Secondary	Clinician rated symptom severity using the Clinical Global Impression scale		Repeated measures up to 6 months after initiation of folic acid/placebo	No
Secondary	Health status using the SF12		Repeated measures up to 6 months after initiation of folic acid/placebo	No
Secondary	Adverse events		Repeated measures up to 6 months after initiation of folic acid/placebo	Yes
Secondary	Cost Utility using the EuroQol, resource use questionnaire and medication history		Repeated measures up to 6 months after initiation of folic acid/placebo	No
Secondary	Folate status		Baseline, 3 months and 6 months	Yes
Secondary	Homocysteine Status		Baseline, 3 months and 6 months	No
Secondary	The interaction between any of the genetic polymorphisms in the folate pathway that predicts the severity of depression, response to antidepressants, and the response to folate supplementation		Baseline only	No
Secondary	Compliance - using the number of tablets remaining at each follow up, dispensing records for folic acid or placebo, dates of repeat prescriptions, Morisky questionnaire, red cell folate and homocysteine levels		12 weeks and 6 months	No

External Links

•   Funder website
•   Trial website