. 2019 Apr 19;31(2):85–97. doi: 10.1089/acu.2019.1337

Table 3A.

Summary of Findings—Primary Analysis

*Prophylactic Drug Treatment vs. Placebo* Study risk of bias: Low risk of bias Patients or populations: Male & female participants with common or classic episodic migraine & no comorbidities Settings: Neurologic, psychiatric, or migraine clinics Interventions: Flunarizine, metoprolol, or valproic-acid capsule Comparison: Placebo capsule
Outcomes	Intervention	# of participants & list of studies	Quality of the evidence per GRADE^a–h
Outcomes	Results with prophylactic drug treatment	# of participants & list of studies	Quality of the evidence per GRADE^a–h
Headache frequency at a 3-month follow-up	7 studies reported a significant reduction in headache frequency at a 3-month follow-up in the prophylactic drug treatment group, compared to the placebo group *Reductions in frequency of migraine attacks:* Frenken & Nuijten, 1984¹⁵ (P = 0.029; flunarizine MD: 1.2; placebo MD: 0.4) Louis, 1981¹⁶ (P < 0.001; flunarizine pretreatment median: 7 [range: 6–14]; flunarizine post-treatment median: 2 [range: 0–5]; placebo pretreatment median: 7 [range: 6–12]; placebo post-treatment median: 3 [range: 2–5]) Mendenopoulos et al., 1985¹⁷ (P = 0.033; NNT: 1.23) Sørenson et al., 1986¹⁸ (P = 0.002; NNT: 2.5) Sorge et al., 1988¹⁹ (P < 0.001; flunarizine MD: 1.7; placebo MD: 0.7) Andersson et al., 1983²¹ (P < 0.05; flunarizine MD: 1.3; placebo MD: 0.53) Reductions in migraine days: Steiner et al., 1988²² (P = 0.05; metoprolol pretreatment mean: 7.1 [SD]: 3.8); metoprolol post-treatment mean: 5.2 [SD: 4.1]; placebo pretreatment mean: 6.5 [SD: 3.4]; placebo post-treatment mean: 5.5 [SD: 2.7])	335 (in 7 studies) Frenken & Nuijten, 1984¹⁵ Louis, 1981¹⁶ Mendenopoulos et al., 1985¹⁷ Sørensen et al., 1986¹⁸ Sorge et al., 1988¹⁹ Andersson et al., 1983²¹ Steiner et al., 1988²²	High Limitations: 0 Imprecision: 0 Inconsistency: 0 Indirectness: 0 Other: 0A
Headache frequency at a 6-month follow-up	N/A	N/A	N/A
Response (at least 50% reduction of headache frequency) at a 3-months follow-up	N/A	N/A	N/A
Response (at least 50% reduction of headache frequency) at a 6-month follow-up	N/A	N/A	N/A

^{^a}

Evidence from randomized controlled trials are initially classified as high quality and then downgraded based on five criteria: (1) limitations in design; (2) imprecision of results; (3) inconsistency of results; (4) indirectness of evidence; and (5) high probability of publication bias.

^{^b}

Evidence from observational studies are initially classified as low quality and then upgraded based on three criteria: (1) large magnitude of effect; (2) all plausible confounders would reduce a demonstrated effect when results show no effect; (3) dose–response gradient.

^{^c}

Evidence obtained from study designs with a high risk of bias.

^{^d}

Evidence obtained from different study designs.

^{^e}

No direct comparison of therapeutic dose with sham therapy.

^{^f}

Lack of allocation concealment and blinding.

^{^g}

Small study group.

^{^h}

GRADE Working Group grades of evidence:

High quality: Further research is very unlikely to change confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on confidence in the estimate of effect and might change the estimate.

Low quality: Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate.

Very low quality: The reviewers are very uncertain about the estimate.

GRADE, Grading of Recommendations Assessment, Development, and Evaluation scale; MD, mean difference; NNT, number needed to treat; SD, standard deviation; NA, not available (i.e., no available data).