Clinical trial NCT00514410: Folate Augmentation of Treatment - Evaluation for Depression: a Randomised Controlled Trial
Official title: Folate Augmentation of Treatment - Evaluation for Depression: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Keywords: Depression
Folate
Folic acid
Antidepressants
Lead sponsor: Bangor University
Sponsor class: OTHER
Collaborators: name: NHS Health Technology Assessment Programme
name: Swansea University
name: Cardiff University
name: University of Liverpool
name: North West Wales NHS Trust
name: North East Wales NHS Trust
name: Swansea NHS Trust
First posted: 2007-08-10
Enrollment: 730
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Self rated symptoms of depression using the Beck Depression Inventory
timeFrame: Repeated measures up to 6 months after initiation of folic acid/placebo
Secondary outcomes:
measure: Clinician rated depression using the Montgomery-Asberg Depression Rating Scale
timeFrame: Repeated measures up to 6 months after initiation of folic acid/placebo
measure: Clinician rated symptom severity using the Clinical Global Impression scale
timeFrame: Repeated measures up to 6 months after initiation of folic acid/placebo
measure: Health status using the SF12
timeFrame: Repeated measures up to 6 months after initiation of folic acid/placebo
measure: Adverse events
timeFrame: Repeated measures up to 6 months after initiation of folic acid/placebo
measure: Cost Utility using the EuroQol, resource use questionnaire and medication history
timeFrame: Repeated measures up to 6 months after initiation of folic acid/placebo
measure: Folate status
timeFrame: Baseline, 3 months and 6 months
measure: Homocysteine Status
timeFrame: Baseline, 3 months and 6 months
measure: 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
timeFrame: Baseline only
measure: 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
timeFrame: 12 weeks and 6 months
Other outcomes:
Locations:
city: Bangor
country: United Kingdom
facility: North West Wales Trust
state: Gwynedd
city: Swansea
country: United Kingdom
facility: Swansea University
city: Wrexham
country: United Kingdom
facility: Cardiff University
Study officials:
affiliation: Swansea University
name: Ian T Russell, PhD, HonFRCGP, FRCP Edin, FFPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Swansea University
name: Keith Lloyd, MBBS, MSc, MRC Psych, MSc, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1186/1471-244X-7-65.