Pizotifen for the treatment of migraine. A systematic review and meta-analysis

Authors

DOI:

https://doi.org/10.48208/HeadacheMed.2021.31

Keywords:

Migraine, Pizotifen, Headache, Systematic review, Evidence-based medicine

Abstract

Introduction

Pizotifen is an oral drug developed many years ago for the prophylaxis of migraine. Trials on pizotifen are decades old, and there has never been a systematic review and meta-analyses of data from these clinical studies.

Methods

This is a systematic review and meta-analyses on pizotifen's efficacy and safety for prophylactic migraine treatment. We considered for inclusion only randomized clinical trials (RCTs). A comprehensive electronic search was performed without language, date or publication status restrictions in the formal electronic databases, clinical trial registration platforms and grey literature.

Results

There were eight RCTs of pizotifen compared either to placebo or to other drugs. Very low certainty of evidence showed that pizotifen seems to be superior to placebo regarding clinical symptoms improvement (Relative risk [RR] 6.00; 95% Confidence interval [CI] 1.63 to 22.03; p = 0.007), but not inferior to naproxen, flunarizine, valproate or clonidine. Weight gain was the most frequent adverse event of pizotifen but there was no difference with placebo (RR 1.92; 95% CI 0.30 to 12.38; 2 RCTs; 142 participants; I2 = 67%; p = 0.49).

Conclusion

The RCTs of pizotifen were decades old. It is a safe and potentially efficacious inexpensive drug that deserves a better designed, modern clinical trial before being dismissed as an option for migraine therapy. PROSPERO Register: CRD42020194347.

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References

Woldeamanuel YW and Cowan RP. Migraine affects 1 in 10 people worldwide featuring recent rise: A systematic review and meta-analysis of community-based studies involving 6 million participants. J Neurol Sci 2017;372:307-315 Doi:10.1016/j.jns.2016.11.071 DOI: https://doi.org/10.1016/j.jns.2016.11.071

Leonardi M and Raggi A. A narrative review on the burden of migraine: when the burden is the impact on people's life. J Headache Pain 2019;20(1):41 Doi:10.1186/s10194-019-0993-0 DOI: https://doi.org/10.1186/s10194-019-0993-0

Silberstein SD, Lee L, Gandhi K, Fitzgerald T, Bell J and Cohen JM. Health care Resource Utilization and Migraine Disability Along the Migraine Continuum Among Patients Treated for Migraine. Headache 2018;58(10):1579-1592 Doi:10.1111/head.13421 DOI: https://doi.org/10.1111/head.13421

Kokoti L, Drellia K, Papadopoulos D and Mitsikostas DD. Placebo and nocebo phenomena in anti- CGRP monoclonal antibody trials for migraine prevention: a meta-analysis. J Neurol 2020;267(4):1158-1170 Doi:10.1007/s00415-019-09673-7 DOI: https://doi.org/10.1007/s00415-019-09673-7

Higgins JPT TJ, Chandler J, Cumpston M, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.0. [Internet]. 2019. Available from: www.training.cochrane.org/handbook. DOI: https://doi.org/10.1002/9781119536604

Moher D, Liberati A, Tetzlaff J and Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62(10):1006-1012 Doi:10.1016/j.jclinepi.2009.06.005 DOI: https://doi.org/10.1016/j.jclinepi.2009.06.005

Ouzzani M, Hammady H, Fedorowicz Z and Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Systematic Reviews 2016;5(1):210 Doi:10.1186/s13643-016-0384-4 DOI: https://doi.org/10.1186/s13643-016-0384-4

Higgins JPT, Thompson SG, Deeks JJ and Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-560 Doi:10.1136/bmj.327.7414.557 DOI: https://doi.org/10.1136/bmj.327.7414.557

Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P and Schünemann HJ. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Bmj 2008;336(7650):924-926 Doi:10.1136/bmj.39489.470347.AD DOI: https://doi.org/10.1136/bmj.39489.470347.AD

Ryan RE. BC-105 a new preparation for the interval treatment of migraine--a double blind evaluation compared with a placebo. Headache 1971;11(1):6-18 Doi:10.1111/j.1526-4610.1971.hed110106.x DOI: https://doi.org/10.1111/j.1526-4610.1971.hed110106.x

Starý O, Janský M, Figar S and Stein J. Clinical physiological study of the action of BC 105 (Sandoz, Basle) in the interval therapy of migraine. Eur Neurol 1974;11(6):353-362 Doi:10.1159/000114334 DOI: https://doi.org/10.1159/000114334

Vilming S, Standnes B and Hedman C. Metoprolol and pizotifen in the prophylactic treatment of classical and common migraine. A double-blind investigation. Cephalalgia 1985;5(1):17-23 Doi:10.1046/j.1468-2982.1985.0501017.x DOI: https://doi.org/10.1046/j.1468-2982.1985.0501017.x

Kangasniemi P. Placebo, 1-isopropylnoradrenochrome-5-monosemicarbazono and pizotifen in migraine prophylaxis. Headache 1979;19(4):219-222 Doi:10.1111/j.1526-4610.1979.hed1904219.x DOI: https://doi.org/10.1111/j.1526-4610.1979.hed1904219.x

Lance JW, Anthony M and Somerville B. Comparative trial of serotonin antagonists in the management of migraine. Br Med J 1970;2(5705):327-330 Doi:10.1136/bmj.2.5705.327 DOI: https://doi.org/10.1136/bmj.2.5705.327

Hübbe P. The prophylactic treatment of migraine with an antiserotonin pizotifen. Acta Neurol Scand 1973;49(1):108-114 Doi:10.1111/j.1600-0404.1973.tb01282.x DOI: https://doi.org/10.1111/j.1600-0404.1973.tb01282.x

Havanka-Kanniainen H, Hokkanen E and Myllylä VV. Efficacy of nimodipine in comparison with pizotifen in the prophylaxis of migraine. Cephalalgia 1987;7(1):7-13 Doi:10.1046/j.1468-2982.1987.0701007.x DOI: https://doi.org/10.1046/j.1468-2982.1987.0701007.x

Dalsgaard-Nielsen T and Ulrich J. Long-term effect and tolerance during prophylactic treatment of migraine with a benzo-cycloheptathiophene derivative, pizotifen. Headache 1973;13(1):12-18 Doi:10.1111/j.1526-4610.1973.hed1301012.x DOI: https://doi.org/10.1111/j.1526-4610.1973.hed1301012.x

Carroll JD and Maclay WP. Pizotifen (BC 105) in migraine prophylaxis. Curr Med Res Opin 1975;3(2):68-71 Doi:10.1185/03007997509113649 DOI: https://doi.org/10.1185/03007997509113649

Andersson PG. BC-105 and deseril in migraine prophylaxis (A double-blind study). Headache 1973;13(2):71-73 Doi:10.1111/j.1526-4610.1973.hed1302068.x DOI: https://doi.org/10.1111/j.1526-4610.1973.hed1302068.x

Arthur GP and Hornabrook RW. The treatment of migraine with BC 105 (pizotifen): a double blind trial. N Z Med J 1971;73(464):5-9

Bademosi O and Osuntokun BO. Pizotifen in the management of migraine. Practitioner 1978;220(1316):325-327

Barolin GS. Long-term therapy of persistent migraine with BC-105. Z Allgemeinmed 1970;46(22):1130-1133

Behan PO. Pizotifen in the treatment of severe recurrent headache single and divided dose therapy compared. Br J Clin Pract 1982;36(1):13-17

Behan PO. Prophylactic Treatments for Migraine — A Comparison of Pizotifen and Clonidine. Cephalalgia 1985;5(3 suppl):524-525 Doi:10.1177/03331024850050S3206 DOI: https://doi.org/10.1177/03331024850050S3206

Behan P, Connelly K and Pain F. Prophylaxis of migraine: a comparison between naproxen sodium and pizotifen. Headache 1986;26(5):237-239 Doi:10.1111/j.1526-4610.1986.hed2605237.x DOI: https://doi.org/10.1111/j.1526-4610.1986.hed2605237.x

Bellavance AJ and Meloche JP. A comparative study of naproxen sodium, pizotyline and placebo in migraine prophylaxis. Headache 1990;30(11):710-715 Doi:10.1111/j.1526-4610.1990.hed3011710.x DOI: https://doi.org/10.1111/j.1526-4610.1990.hed3011710.x

Cerbo R, Casacchia M, Formisano R, Buzzi MG, Boni B, Feliciani M, . . . Agnoli A. Double-blind clinical study: flunarizine versus pizotifen in a single nightly dose in hemicrania patients. Riv Neurol 1985;55(2):139-146

Chitsaz A, Najafi MR, Zangeneh FA, Norouzi R, Mehri Salari M. Pizotifen in migraine prevention: A comparison with sodium valproate. Neurology Asia 2012;17(4):319-24.

Lawrence ER, Hossain M and Littlestone W. Sanomigran for migraine prophylaxis, controlled multicenter trial in general practice. Headache 1977;17(3):109-112 Doi:10.1111/j.1526-4610.1977.hed1703109.x DOI: https://doi.org/10.1111/j.1526-4610.1977.hed1703109.x

Louis P and Spierings EL. Comparison of flunarizine (Sibelium) and pizotifen (Sandomigran) in migraine treatment: a double-blind study. Cephalalgia 1982;2(4):197-203 Doi:10.1046/j.1468-2982.1982.0204197.x DOI: https://doi.org/10.1046/j.1468-2982.1982.0204197.x

Rascol A, Montastruc JL and Rascol O. Flunarizine versus pizotifen: a double-blind study in the prophylaxis of migraine. Headache 1986;26(2):83-85 Doi:10.1111/j.1526-4610.1986.hed2602083.x DOI: https://doi.org/10.1111/j.1526-4610.1986.hed2602083.x

Mennini FS, Gitto L and Martelletti P. Improving care through health economics analyses: cost of illness and headache. J Headache Pain 2008;9(4):199-206 Doi:10.1007/s10194-008-0051-9 DOI: https://doi.org/10.1007/s10194-008-0051-9

Stokes M, Becker WJ, Lipton RB, Sullivan SD, Wilcox TK, Wells L, . . . Blumenfeld AM. Cost of health care among patients with chronic and episodic migraine in Canada and the USA: results from the International Burden of Migraine Study (IBMS). Headache 2011;51(7):1058-1077 Doi:10.1111/j.1526-4610.2011.01945.x DOI: https://doi.org/10.1111/j.1526-4610.2011.01945.x

Negro A, Sciattella P, Rossi D, Guglielmetti M, Martelletti P and Mennini FS. Cost of chronic and episodic migraine patients in continuous treatment for two years in a tertiary level headache Centre. J Headache Pain 2019;20(1):120 Doi:10.1186/s10194-019-1068-y DOI: https://doi.org/10.1186/s10194-019-1068-y

Linde M, Gustavsson A, Stovner LJ, Steiner TJ, Barré J, Katsarava Z, . . . Andrée C. The cost of headache disorders in Europe: the Eurolight project. Eur J Neurol 2012;19(5):703-711 Doi:10.1111/j.1468-1331.2011.03612.x DOI: https://doi.org/10.1111/j.1468-1331.2011.03612.x

Mansfield C, Gebben DJ, Sutphin J, Tepper SJ, Schwedt TJ, Sapra S and Shah N. Patient Preferences for Preventive Migraine Treatments: A Discrete-Choice Experiment. Headache 2019;59(5):715-726 Doi:10.1111/head.13498 DOI: https://doi.org/10.1111/head.13498

Johnson CH, Morgan M, O’Bryan S, Patel H and Smiley J. Drugs in Pregnancy. [Internet]. 2008. Available from: https://jfmo.cchs.ua.edu/files/2013/09/Drugs_Pregnancy.pdf

Vo P, Wen S, Martel MJ, Mitsikostas D, Reuter U and Klatt J. Benefit-risk assessment of erenumab and current migraine prophylactic treatments using the likelihood of being helped or harmed. Cephalalgia 2019;39(5):608-616 Doi:10.1177/0333102418801579 DOI: https://doi.org/10.1177/0333102418801579

Robblee J, Devick KL, Mendez N, Potter J, Slonaker J and Starling AJ. Real-World Patient Experience With Erenumab for the Preventive Treatment of Migraine. Headache 2020;60(9):2014-2025 Doi:10.1111/head.13951 DOI: https://doi.org/10.1111/head.13951

Internacional Headache Society. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38(1):1-211 Doi:10.1177/0333102417738202 DOI: https://doi.org/10.1177/0333102417738202

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Published

2021-10-26

How to Cite

1.
Fragoso YD, Lopes GCM, Santos GM, Carturan P, Martimbianco ALC. Pizotifen for the treatment of migraine. A systematic review and meta-analysis. Headache Med [Internet]. 2021 Oct. 26 [cited 2024 Mar. 29];12(3):168-81. Available from: https://headachemedicine.com.br/index.php/hm/article/view/461

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