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 high-dose riboflavin in migraine prophylaxis. A randomised controlled trial.
Neurology. 1998; 50: 466-70.
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 Evidence-Based General Practice
Citation
Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomised controlled trial.
Neurology. 1998; 50: 466-70.
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 co-intervention.
- 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 (1-mathit{CER})}{text{# of control pts.}} + frac{mathit{EER}times(1-mathit{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 high-dose riboflavin in migraine prophylaxis. A randomised controlled trial.
Neurology. 1998; 50: 466-70.
Clinical Question
Is riboflavin effective in preventing migraine?
Search Terms
migraine AND riboflavin
The Study
- Double-blinded concealed randomised controlled trial with intention-to-treat.
- 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 |
|---|---|---|---|---|---|---|
| Non-responder (<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 2-3 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
