Evidence Table 10Efficacy of Other Serotoninergic Agents1,2

StudyTreatment# of patients improved/N (%)Odds ratioMean ValuesEffect size or p-value
NBefore TreatmentAfter Treatment
COMPARISONS WITH PLACEBO (AND DOSING STUDIES)
Pizotifen
Arthur and Hornabrook, 1971Pizotifen, 3 mg/day for 1 mo21/52 (40%)5.2 (1.9 to 14.3)
≥ 50% reduction in HF
52*--p < 0.005 (pizotifen better)
HF
Placebo6/52 (12%)52*--
Bellavance and Meloche, 1990Pizotifen, 1.5 mg/day for 3 mos--585.773.27n.s. (no p-value reported)
HI
Placebo-525.565.08
Carroll and Maclay, 1975Pizotifen, 1.5 to 3 mg/day for 2 mos--14*---
Placebo-14*--
Hughes and Foster, 1971Pizotifen, 3 mg/day for 6 wks--26*18.118.5n.s. (no p-value reported)
HF
Placebo (lactose)-26*18.120.3
Krakowski and Engisch, 1973Pizotifen, 6 mg/day for 12 wks--1331.816.80.90 (0.01 to 1.8)
HI
Placebo-936.232.8
Lance and Anthony, 1968Pizotifen, 3 mg/day for 1 mo12/25 (48%)1.6 (0.53 to 5.1)
≥ 50% reduction in either HF or HA intensity
25--n.s. (p = 0.4)
HF or HA intensity
Placebo9/25 (36%)25--
Lawrence, Hossain, and Littlestone, 1977Pizotifen, 3 mg/day for 10 wks--14-8.60.62 (−0.14 to 1.4)
HI
Placebo-14-14.9
Osterman, 1977Pizotifen, 3 mg/day for 8 wks12/27 (44%)-27*-1.60.95 (0.38 to 1.5)
HI
Placebo-27*-2.4
Ryan, 1968Pizotifen, 4 mg/day--62*-8.9-
HI
Placebo-62*-17.0
Ryan, 1971Pizotifen, dose increased from 0.5 mg/day to 3 mg/day for 2 wks; after 2 wks, and at 4-wk intervals, dosage adjusted according to a protocol for 10 wks--2521.5315.68-
HI
Placebo-2010.006.65
Sjaastad and Stensrud, 1969Pizotifen, 4 mg/day for 8 wks9/20 (45%)-20*-5.61.1 (0.36 to 1.7)
HF
Placebo-20*-9.9
Tropisetron
Ferrari, Wilkinson, Hirt, et al., 1991
Study 1
Tropisetron, 50 mg/day for 3 mos13/45 (29%)0.60 (0.25 to 1.4)
≥ 50% reduction in either HF or HI
45--n.s. (p > 0.05)
HF
Placebo19/47 (40%)47--
Ferrari, Wilkinson, Hirt, et al., 1991
Study 1
Tropisetron, 25 mg/day for 3 mos16/43 (37%)0.87 (0.37 to 2.0)
≥ 50% reduction in either HF or HI
43--n.s. (p > 0.05)
HF
Placebo19/47 (40%)47--
Ferrari, Wilkinson, Hirt, et al., 1991
Study 2
Tropisetron, 15 mg/day for 3 mos17/30 (57%)2.4 (0.70 to 8.2)
≥ 50% reduction in either HF or HI
30--n.s. (p> 0.05)
HF
Placebo6/17 (35%)17--
Ferrari, Wilkinson, Hirt, et al., 1991
Study 1
Tropisetron, 50 mg/day for 3 mos13/45 (29%)0.69 (0.28 to 1.7)
≥ 50% reduction in either HF or HI
45---
Tropisetron, 25 mg/day for 3 mos16/43 (37%)43--
Lisuride
Herrmann, Krištof, and Sastre y Hernandez, 1978Lisuride, 0.075 mg/day for 6 mos--103--p = 0.05 (lisuride better)
HF
Placebo-111--
Sances, Martignoni, Rosettino, et al., 1989Lisuride, 0.15 mg/day for 3 mos--2081.747.30.76 (0.12 to 1.4)
HI
Placebo-2010295.8
Somerville and Herrmann, 1978Lisuride, 0.075 mg/day for 3 mos--58--p < 0.05 (lisuride better)
HF
Placebo-52--
Zuddas, Mulas, Del Zompo, et al., 1985Lisuride, 0.075 mg/day for 3 mos--15---
Placebo-15--
Wilkinson, Agnoli, Gerber, et al., 1989Lisuride, 0.15 mg/day for 3 mos18/49 (37%)0.98 (0.42 to 2.3)
≥ 50% reduction in HF
49--n.s. (p > 0.05)
HI
Lisuride, 0.075 mg/day for 3 mos16/43 (37%)43--
Oxitriptan
De Benedittis and Massei, 1986Oxitriptan, 400 mg/day for 2 mos--31*43.825.10.08 (−0.42 to 0.58)
HI
Placebo-31*43.826.5
Kangasniemi, Falck, Långvik, et al., 1978Oxitriptan, 2000 mg/day for 3 mos--8*-16.0−0.45 (−0.54 to 1.4)
HI
Placebo (levoleucine), 1280 mg/day for 3 mos-8*-23.8
Mathew, 1978Oxitriptan, 300 mg/day for 8 wks--12*---
Placebo-12*--
Iprazochrome
Osterman, 1977Iprazochrome, 15 mg/day for 8 wks6/27 (22%)-27*-2.1n.s. (no p-value reported)
HI
Placebo-27*-2.4
COMPARISONS AMONG SEROTONIN ANTAGONISTS
Pizotifen VS. iprazochrome
Osterman, 1977Pizotifen, 3 mg/day for 8 wks12/27 (44%)2.8 (0.86 to 9.1)
≥ 50% reduction in HF
27*-1.60.73 (0.18 to 1.3)
HI
Iprazochrome, 15 mg/day for 8 wks6/27 (22%)27*-2.1
Kangasniemi, 1979Pizotifen, 1.5 mg/day for 3 mos--34*-2.70.26 (−0.22 to 0.73)
HI
Iprazochrome, 15 mg/day for 3 mos-34*-3.2
Pizotifen vs. lisuride
Nattero, Biale, Savi, et al., 1991Pizotifen, 4.5 mg/day for 16 wks10/43 (23%)0.57 (0.22 to 1.5)
≥ 50% reduction in HF
43*---
HF
Lisuride, 0.225 mg/day for 16 wks15/43 (35%)43*--
Pizotifen vs. oxitriptan
Bono, Criscuoli, Martignoni, et al., 1982Pizotifen, 1.40 mg/day for 2 mos--34--p < 0.02 (pizotifen better)
HI
Oxitriptan, 400 mg/day for 2 mos-33--
COMPARISONS WITH CALCIUM ANTAGONISTS
Pizotifen vs. flunarizine
Cerbo, Casacchia, Formisano, et al., 1986Pizotifen, 1.5 mg/day for 2 mos--21*--n.s. (no p-value reported)
HF
Flunarizine, 15 mg/day for 2 mos-21*--
Louis and Spierings, 1982Pizotifen, 2–3 mg/day for 4 mos--30--n.s. (no p-value reported)
HF
Flunarizine, 10 mg/day for 4 mos-36--
Rascol, Montastruc, and Rascol, 1986Pizotifen, 2.19 mg/day for 4 mos--14--n.s. (no p-value reported)
HF
Flunarizine, 10 mg/day for 4 mos-21--
Pizotifen vs. nimodipine
Gawel, 1987Pizotifen, 3 mg/day for 3 mos--54*7.556.650.11 (−0.42 to 0.64)
HF
Nimodipine, 120 mg/day for 3 mos-54*7.566.04
Havanka-Kanniainen, Hokkanen, and Myllylä, 1987Pizotifen, 1.5 mg/day for 3 mos--43*6.22.6−0.11 (−0.54 to 0.31)
HF
Nimodipine, 120 mg/day for 3 mos-43*6.22.3
Micieli, Trucco, Agostinis, et al., 1985Pizotifen, 1.5 mg/day for 3 mos--20*--n.s. (no p-value reported)
HI
Nimodipine, 120 mg/day for 3 mos-20*--
Pizotifen vs. cyclandelate
Mastrosimone, laccarino, and de Caterina, 1992Pizotifen, 1.5 mg/day for 3 mos--26--p < 0.001 (cyclandelate better)
Total pain index
Cyclandelate, 1600 mg/day for 3 mos-35--
COMPARISONS WITH METHYSERGIDE
Pizotifen vs. methysergide
Andersson, 1973Pizotifen, 2.0 mg/day for 3 mos18/47 (38%)1.4 (0.59 to 3.2) > 50% reduction in HF49*5.93.50.17 (−0.23 to 0.57)
HF
Methysergide, 4 mg/day for 3 mos15/48 (31%)49*5.94.1
Forssman, Henriksson, and Kihlstrand, 1972Pizotifen, 2–3 mg/day for 10 wks--17*3.52.1n.s. (no p-value reported)
HI
Methysergide, 4–6 mg/day for 10 wks-17*3.51.8
Presthus, 1971Pizotifen, 1.5 mg/day for 5 wks--19*--0.29 (−0.17 to 0.76)
HF
Methysergide, 3 mg/day for 5 wks-19*--
Ryan, 1968Pizotifen, 4 mg/day for 4 wks--62*-8.9-
HI
Methysergide, 4 mg/day for 4 wks62*-11.3
Oxitriptan vs. methysergide
Sicuteri, 1973Oxitriptan, 200 mg/day for 40 days--20-5.6 (mean within- patient, pre- to - post-treatment)−0.09 (−0.71 to 0.53)
HI
Methysergide, 2 mg/day for 40 days-20-5.9 (mean within- patient, pre- to - post-treatment)
Titus, Davalos, Alom, et al., 1986Oxitriptan, 600 mg/day for 6 mos32/45 (71%)0.82 (0.31 to 2.2)
≥50% reduction in HF or frequency of severe HAs
45---
Methysergide, 3 mg/day for 6 mos30/40 (75%)40--
Lisuride vs. methysergide
Herrmann, Horowski, Dannehl, et al., 1977Lisuride, 75 mcg/day for 3 mos38/72 (53%)1.1 (0.53 to 2.2)
≥50% reduction in HF
72---
Methysergide, 6 mg/day for 3 mos27/53 (51%)53--
COMPARISON WITH ALPHA-2 AGONIST
Pizotifen vs. clonidine
Behan, 1985Pizotifen (Sanomigran®), 1.5 mg/night for 1 mo; 1.5 – 3.0 mg/night for 2d mo--18---
Clonidine (Dixarit®), 100 μg/day for 1 mo; 100–150 μg/day for 2d mo-26--
COMPARISON WITH ANTINAUSEANT
Pizotifen vs. prochlorperazine
Hübbe, 1973Pizotifen, 3 mg/day for 2 mos--40*--n.s. (no p-value reported)
HF
Prochlorperazine, 15 mg/day for 2 mos-40*--
COMPARISON WITH BETA-BLOCKER
Pizotifen vs. metoprolol
Vilming, Standnes, and Hedman, 1985Pizotifen, 0.5 mg/day, gradually increased to 1.5 mg/day for 8 wks14/33 (42%)1.8 (0.64 to 4.9)
≥50% reduction in HI
30*13.0 (median)7.1 (median)n.s. (p > 0.05)
HI
Metoprolol, 100 mg/day for 8 wks10/34 (29%)30*13.0 (median)8.6 (median)
COMPARISON WITH NSAID
Pizotyline vs. naproxen sodium
Bellavance and Meloche, 1990Pizotyline, 1.5 mg/day for 3 mos--585.773.27n.s. (no p-value reported)
HI
Naproxen sodium, 1100 mg/day for 3 mos-565.322.85
1

Key to abbreviations: HA = headache; HF = headache frequency; HI = headache index; mog = microgram; mg = milligram; mo = month; N = population studied (n = sample size); n.s. = not (statistically) significant; N/S = not specified; wk = week; μg = microgram

2

An asterisk denotes a crossover trial.

From: Evidence Tables

Cover of Drug Treatments for the Prevention of Migraine Headache
Drug Treatments for the Prevention of Migraine Headache.
Technical Reviews, No. 2.3.
Gray RN, Goslin RE, McCrory DC, et al.

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