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Table 1 Antihistamines in migraine prophylaxis

From: Histamine and migraine revisited: mechanisms and possible drug targets

Type (Ligand) Participants Daily dose Duration Main findings First author (year)
H1 antagonist (cyproheptadine) vs. 5HT antagonist (methysergide) vs. Bellergalb vs. placebo 453a 12–24 mg 6 mg NA NA 6 months Clinical improvement (Headache free or substantial improvement)c: methysergide 64%, cyproheptadine 46%, Bellergal 34%, placebo 20%. Curran (1964) (12)
Antihistaminic drug (pizotifen) 32a 1.5–2 mg NA Cessation or attenuation of attacks in 33%. Significant reduction in migraine days and increased response to acute medication in 40%. Increased resilience against induced attacks. AEd: weight gain and drowsiness. Sicuteri (1967) (13)
Antihistaminic drug (pizotifen) 11 MAe
27 MOf
2 Cluster headache
1.5 mg
(1–3 mg)
2–6 mo: 16
> 6 mo: 17
Significant (42.5%) clinical improvement compared to previous placebo reports (Curran 1964). Selby (1970) (14)
H1 antagonist (cyproheptadine) vs. antihistaminic drug (pizotifen) vs. antihistaminic drug (methdilazine) 165a 12–24 mg
4.5–9 mg
16–32 mg
4 weeks Clinical improvement: pizotifen 58%, methdilazine 41%, cyproheptadine 40% No placebo control. Lance (1970) (15)
Antihistaminic drug (pizotifen) vs. 5HT antagonist (divascan) vs placebo 4 MAe
26 MOf
3 mg
15 mg
8 weeks Significant lowered attack rate with pizotifen.
AEd: weight gain and drowsiness.
Osterman (1977) (16)
Antihistaminic drug (pizotifen) vs placebo 28a 3 mg 12 weeks Complete resolution in 6 cases, reduced frequency and severity in 6 and no improvement in 2 cases. No improvement in the placebo group. AEd: weight gain and dizziness. Lawrence (1977) (17)
H2 (cimetidine) vs. H2 and H1 combined (cimetidine and chlorpheniramine) vs. placebo 24 MO
1 basilar migraine
200 mg cimetidine
4 mg chlor pheniramine
1 week No significant improvement over placebo with H2 antagonist alone or in combination with H1antagonist.
AEd: weight gain and drowsiness.
Anthony (1978) (18)
H2 (cimetidine) vs. H2 and H1 combined (cimetidine and chlorpheniramine) vs. placebo 6 MA
28 MO
200 mg cimetidine
4 mg chlor-pheniramine
12 weeks No significant improvement over placebo with H2 antagonist alone or in combination with H1antagonist.
AEd: weight gain and drowsiness.
Nanda (1980) (20)
H1 (cinnarizine) 11MAe
69 MOf
75 mg 14 weeks Significant reduction in migraine days and use of acute medication. AEd: weight gain, drowsiness, mild reversible depression and dyspepsia.
Open label. Dropout rate 3.75%.
Rossi (2003) (22)
H1 (cinnarizine) 60g Up to 75 mg 12 weeks Significant reduction in migraine days. AEd: Palpitations and dizziness.
Open label. Dropout rate 5%.
Togha (2006) (21)
H1 (cinnarizine) vs valproate 86 MOf
18 MAe
50 mg Cinnarizine
400 mg valproate
12 weeks Valproate more effective than cinnarizine.
AEd: Dry mouth, fatigue and somnolens as the most frequent. No placebo control. Dropout rate: 23% cinnarizine, 19.4% valproate.
Bostani (2013) (23)
H1 (cinnarizine) vs placebo 68 children (5-17y)a 50 mg or 1.5 mg/kg(> 30 kg) 12 weeks Significant better than placebo to reduce headache frequency by at least 50% reduction. AEd: weight gain and drowsiness.
Dropout rate: 12% cinnarizine, 5% placebo.
Ashrafi (2014) (24)
  1. aNo subtype stated
  2. bMixture of phenobarbitone 20 mg, ergotamine tartrate 0.3 mg and belladonna alkaloids 0.1 mg
  3. cNot placebo corrected
  4. dAdverse effects
  5. eMigraine with aura
  6. fMigraine without aura
  7. gSubtype unknown