A middle aged woman presented with exacerbation of her usual pattern of migraine. She asked specifically about whether riboflavin might help as she had heard from a friend that it helped prevent migraine. Together you formulate the question, in patients with frequent migraines , is riboflavin effective in the reduction of migraine frequency or severity?
Searching terms and evidence source:
Since this is a question of intervention, a randomised trial would be ideal. The most comprehensive and easy to check source is the Controlled Clinical Trials Registry (CCTR) in the Cochrane Library. I used the terms “migraine and riboflavin” (no methodological filters are needed as only list controlled trials).This gives 2 hits, one of which is: Schoenen J, Jacquy J, Lenaerts M. Effectiveness of highdose riboflavin in migraine prophylaxis. A randomised controlled trial.
Neurology. 1998; 50: 46670.
Read the article and decide:
 Is the evidence from this trial valid?
 If valid, is this evidence important?
 If valid and important, can you apply this evidence in caring for your patient?
Completed Therapy Worksheet for EvidenceBased General Practice
Citation
Schoenen J, Jacquy J, Lenaerts M. Effectiveness of highdose riboflavin in migraine prophylaxis. A randomised controlled trial.
Neurology. 1998; 50: 46670.
Are the results of this single preventive or therapeutic trial valid?
 Was the assignment of patients to treatments randomised?
 And was the randomisation list concealed?
 Yes
 Were all patients who entered the trial accounted for at its conclusion?
 And were they analysed in the groups to which they were randomised?
 Yes.
1 patient was excluded from analysis for a protocol violation.  Were patients and clinicians kept “blind” to which treatment was being received?
 Yes – the trial used a placebo identical to the riboflavin
 Aside from the experimental treatment, were the groups treated equally?
 Yes – again the use of placebo helped control cointervention.
 Were the groups similar at the start of the trial?
 Yes
Are the valid results of this randomised trial important?
Sample Calculations
Occurrence of diabetic neuropathy  Relative Risk Reduction RRR 
Absolute Risk Reduction ARR 
Number Needed to Treat NNT 


Usual Insulin Control Event Rate CER 
Intensive Insulin Experimental Event Rate EER 
(CER – EER)/CER  CER – EER  1/ARR 
9.6%  2.8%  (9.6% – 2.8%)/9.6% = 71% 
9.6% – 2.8% = 6.8% 
1/6.8% = 15 pts 
begin{align}
&text{95% Confidence Interval ($CI$) on an $NNT$}\
&= 1 / (text{limits on the $CI$ of its $ARR$}) \
&= pm 1.96 sqrt{frac{mathit{CER} times (1mathit{CER})}{text{# of control pts.}} + frac{mathit{EER}times(1mathit{EER})}{text{# of exper. pts.}}} \
&= pm 1.96 sqrt{frac{0.096 times 0.904}{730} + frac{0.028times 0.972}{711}} \
&= pm 2.4%
end{align}
Your Calculations
< 50% improvement in migraine frequency at 3 months  Relative Risk Reduction RRR 
Absolute Risk Reduction ARR 
Number Needed to Treat NNT 


CER  EER  (CER – EER)/CER  CER – EER  1/ARR 
81%  46%  43%  35%  3 
Can you apply this valid, important evidence about a treatment in caring for your patient?
Do these results apply to your patient?
 Is your patient so different from those in the trial that its results can’t help you?
 My patient had been having 4 migraines per month, and had had migraines for several years and so fulfilled the criteria.
 How great would the potential benefit of therapy actually be for your individual patient?
 She’d expect to reduce the frequency from 4 to about 2 per month.
1. Method I: f
$$ text{Risk of the outcome in your patient, relative to patients in the trial. expressed as a decimal: }underline{qquad}\
mathit{NNT}/mathit{F} \
= underline{qquad} / underline{qquad} \
= text{($NNT$ for patients like yours)} $$
Are your patient’s values and preferences satisfied by the regimen and its consequences?
 Do your patient and you have a clear assessment of their values and preferences?
 Taking riboflavin once per day would be worth avoiding 2 migraines per month.
Are they met by this regimen and its consequences?
Additional Notes
The reduction in migraine frequency appeared to develop over the 3 months. Patients should not expect an immediate reduction. Riboflavin is available as a sole ingredient (not as a multivitamin) but costs around $10 per month.
Migraine – Riboflavin is effective prophylaxis
Clinical Bottom Line
Treating two patients with migraine with 400mg riboflavin per day will result in one of them having a 50% reduction in migraine frequency, though with no effect on severity.
Citation
Schoenen J, Jacquy J, Lenaerts M. Effectiveness of highdose riboflavin in migraine prophylaxis. A randomised controlled trial.
Neurology. 1998; 50: 46670.
Clinical Question
Is riboflavin effective in preventing migraine?
Search Terms
migraine AND riboflavin
The Study
 Doubleblinded concealed randomised controlled trial with intentiontotreat.
 The Study Patients: recurrent migraines
 Control group (N = 27; 27 analysed): placebo
 Experimental group (N = 28; 28 analysed): riboflavin 400mg daily
The Evidence
Outcome  Time to Outcome  CER  EER  RRR  ARR  NNT 

Nonresponder (<50% reduction)  0.85  0.41  52%  0.440  2  
95% Confidence Intervals  25% to 78%  0.213 to 0.667  2 to 5 
Comments
We have two caveats:
 This is the only study, and has modest numbers (55).
 The effect appeared to take 23 months to build up; patients need to be warned it will not necessarily work immediately.
Appraised By
Paul Glasziou
Email: P.Glasziou@spmed.uq.edu.au