Syllabi - General Practice - Therapy Scenario

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

95% Confidence Interval (CI) on an NNT
= 1 / (limits on the CI of its ARR)
= +-1.96 sqrt(((CERx(1-CER))/(# of control pts.)) + ((EERx(1-EER))/(# of exper. pts.)))
= +-1.96 sqrt(((0.096x0.904)/730) + ((0.028x0.972)/711))
= ±2.4%

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

Risk of the outcome in your patient, relative to patients in the trial. expressed as a decimal: _____

NNT/F
= ___ /___
= (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