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

Phase 4

Completed

• Conditions: Depression
• Interventions: Drug: Folic Acid; Drug: Placebo

• Registration Number: NCT00514410
• Lead Sponsor: Bangor University

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-08-09
• Study First Submitted QC: 2007-08-09
• Study First Posted: 2007-08-10
• Status Verified: 2009-02
• Primary Completion: 2011-05
• Study Completion: 2011-05
• Last Update Submitted: 2011-10-11
• Last Update Posted: 2011-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 730

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Folic Acid	Folic Acid	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Self rated symptoms of depression using the Beck Depression Inventory	Repeated measures up to 6 months after initiation of folic acid/placebo

Secondary Outcome Measures

Name	Time	Method
Clinician rated depression using the Montgomery-Asberg Depression Rating Scale	Repeated measures up to 6 months after initiation of folic acid/placebo
Clinician rated symptom severity using the Clinical Global Impression scale	Repeated measures up to 6 months after initiation of folic acid/placebo
Health status using the SF12	Repeated measures up to 6 months after initiation of folic acid/placebo
Adverse events	Repeated measures up to 6 months after initiation of folic acid/placebo
Cost Utility using the EuroQol, resource use questionnaire and medication history	Repeated measures up to 6 months after initiation of folic acid/placebo
Folate status	Baseline, 3 months and 6 months
Homocysteine Status	Baseline, 3 months and 6 months
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
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

Trial Locations

Locations (3)

North West Wales Trust; 🇬🇧 Bangor, Gwynedd, United Kingdom

Cardiff University; 🇬🇧 Wrexham, United Kingdom

Swansea University; 🇬🇧 Swansea, United Kingdom