Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial.
BACKGROUND
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.


METHODS
The primary objective of this 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. Seven hundred and thirty patients will be recruited from North East Wales, North West Wales and Swansea. Patients with moderate to severe depression will be referred to the trial by their GP or Psychiatrist. If patients consent they will be assessed for eligibility and baseline measures will be undertaken. Blood samples will be taken to exclude patients with folate and B12 deficiency. Some of the blood taken will be used to measure homocysteine levels and for genetic analysis (with additional consent). Eligible participants will be randomised to receive 5 mg of folic acid or placebo. Patients with B12 deficiency or folate deficiency will be given appropriate treatment and will be monitored in the 'comprehensive cohort study'. Assessments will be at screening, randomisation and 3 subsequent follow-ups.


CONCLUSIONS
If folic acid is shown to improve the efficacy of antidepressants, then it will provide a safe, simple and cheap way of improving the treatment of depression in primary and secondary care.


BACKGROUND
Current controlled trials ISRCTN37558856.
Roberts
Seren Haf
SH
North Wales Section of Psychological Medicine, Institute of Medical and Social Care Research (IMSCaR), Bangor University, Academic Unit, Wrexham Technology Park, Wrexham, LL13 7YP, UK. seren.roberts@new-tr.wales.nhs.uk
Bedson
Emma
E
Hughes
Dyfrig
D
Lloyd
Keith
K
Menkes
David B
DB
Moat
Stuart
S
Pirmohamed
Munir
M
Slegg
Gary
G
Thome
Johannes
J
Tranter
Richard
R
Whitaker
Rhiannon
R
Wilkinson
Clare
C
Russell
Ian
I
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000191:economics; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005194:Family Practice; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D005492:Folic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000191:economics; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D011570:Psychiatry
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D006710:Homocysteine; D005492:Folic Acid