Folate Augmentation of Treatment – Evaluation for Depression (FolATED): randomised trial and economic evaluation

Bedson, Emma; Bell, Diana; Carr, Daniel F.; Carter, Ben; Hughes, Dyfrig; Jorgensen, Andrea; Lewis, Helen J; Lloyd, Kenneth E.; McCaddon, Andrew; Moat, Stuart; Pink, Joshua; Roberts, Seren; Russell, Ian; Sylvestre, Yvonne; Tranter, Richard; Whitaker, Rhiannon; Wilkinson, Clare; Williams, Nefyn

doi:10.3310/hta18480

Cited by 36 publications

(34 citation statements)

References 150 publications

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“…In fact, it is not clear from currently available literature if the effect pertains to individuals with normal folate, to those with low red cell folate, or to those with serum folate deficiency (Bedson et al, 2014;Taylor, Carney, Goodwin, & Geddes, 2004). Additionally, there are concerns that the folate supplementation may mask anemia due to B12 deficiency, whereas other symptoms on account of that deficiency may progress (Coppen & Bolander-Gouaille, 2005;Papakostas et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis

Petridou¹,

Kousoulis²,

Michelakos³

et al. 2015

Aging & Mental Health

110

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Section: Discussionmentioning

confidence: 99%

Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis

Petridou¹,

Kousoulis²,

Michelakos³

et al. 2015

Aging & Mental Health

110

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“…To detect an effect size of 0.35 in these scores with 80% power when using a 5% significance level, required that we analyse at least 250 trial participants. We used the techniques of statistical imputation applied successfully by the Cancer of the Oesophagous or Gastricus: New Assessment of the Technology of Endosonography 58 and Folate Augmentation of Treatment -Evaluation of Depression (FolATED) 59 trials to achieve an effective sample size of 250 for CONSTRUCT.…”

Section: Sample Size and Powermentioning

confidence: 99%

Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

Williams

Alam

Alrubaiy

et al. 2016

Health Technol Assess

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BackgroundThe efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness.ObjectiveTo compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC.MethodBetween May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn’s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1–3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years.ResultsThe 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) –0.0088 to 0.0682;p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI –0.032 to 0.096;p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI –0.0250 to 0.0353;p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188;p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493;p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546;p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917;p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114;p = 0.998); deaths (all three who died received infliximab;p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference –£5632, 95% CI –£8305 to –£2773;p < 0.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin.ConclusionsTotal cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1–3 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin.Trial registrationCurrent Controlled Trials ISRCTN22663589.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 44. See the NIHR Journals Library website for further project information.

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“…The trials by Bedson et al 66 and Christensen et al 67 reported no benefit from the adjunctive use of 5 mg/day of FA for 12 weeks, and 0.4 mg/day of FA with 0.1 mg/day of vitamin B 12 for 24 months, respectively. In the study by Bedson et al, 66 475 participants were included initially (females, 304; males, 171) with the outcome measure, assessed by the BDI-II at 25 weeks, showing no evidence that FA was more effective than the placebo (OR: 1.09; 95% CI: 0.75-1.59; p = 0.65).…”

Section: Folate (Fa And/or L-mthf) As An Adjunct To Antidepressants Imentioning

confidence: 98%

“…75 Two studies examined adults with either depressive symptoms, 67 or moderate to severe depression. 66 Inclusion into the remaining study was based on a diagnosis of Restrictive Anorexia Nervosa or Eating Disorder Not Otherwise Specified. 73 In this study, a food frequency and "3-day food and drink record" also assessed low folate intake.…”

Section: Folate (Fa And/or L-mthf) As An Adjunct To Antidepressants Imentioning

confidence: 99%

“…In the study by Bedson et al, 66 475 participants were included initially (females, 304; males, 171) with the outcome measure, assessed by the BDI-II at 25 weeks, showing no evidence that FA was more effective than the placebo (OR: 1.09; 95% CI: 0.75-1.59; p = 0.65). All other outcome measures showed no significant difference between FA and placebo (p > 0.05), except for the SF-12 mental component for the placebo group (p = 0.017).…”

Section: Folate (Fa And/or L-mthf) As An Adjunct To Antidepressants Imentioning

confidence: 99%

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Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

Barnett¹,

D’Cunha

Georgousopoulou

et al. 2017

Exploratory Research and Hypothesis in Medicine

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Folate has been proposed to be an efficacious treatment strategy for depression. The mandatory fortification of flour with synthetic folic acid (FA) in over 80 countries has yielded improvements in folate intake; however, depression is still a considerable public health concern. While there are established benefits of FA fortification in reducing risk of neural tube defects, the implications regarding depression are unclear, especially in individuals with certain genetic polymorphisms. Therefore, a systematic review was conducted to examine the effects of folate to treat depression. Following PRISMA guidelines, a systematic review was conducted of electronic databases (PUBMED, Scopus, CINAHL, and Cochrane Library) to identify human clinical trials examining the effects of folate (including FA) supplementation in the management or prevention of depression, the impact on inflammatory markers and if genetic polymorphisms were considered. Ten trials met the inclusion criteria. Seven trials examined effects of either adjunctive FA or L-methylfolate (L-MTHF) supplementation with antidepressants in the management of depression and three examined effects of FA supplementation alone for prevention of depression. No benefit of FA was found compared to placebo (all, p > 0.05). The single L-MTHF trial that explored the interplay of genetic polymorphisms and methylation status found benefit in the Hamilton depression rating scale from adjunctive treatment with 15 mg/day of L-MTHF compared with placebo (−6.8 ± 7.2 vs. −3.7 ± 6.5; p = 0.017) and improvement with L-MTHF for most genetic markers. Currently, there is no evidence to support FA supplementation for the management or prevention of depression. More research is required to determine the efficacy of L-MTHF and folinic acid in certain clinical populations.

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Folate Augmentation of Treatment – Evaluation for Depression (FolATED): randomised trial and economic evaluation

Cited by 36 publications

References 150 publications

Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis

Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis

Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

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