• PALANISAMY SIVANANDY Department of Pharmacy Practice, International Medical University, Kuala Lumpur 57000, Malaysia
  • AIDIL NATASHA ROSMAN School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
  • AINAA DIYANA SHAPHERI School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
  • TENG TENG CHEW School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
  • NATALIE JIA XIN LAU School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
  • MICHELLE ZI YIN YEONG School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
  • MICHELLA ONG School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
  • BIBI MUNIIRAH UMMEH HAANI MEETOOA School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
  • ELAINE NG School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
  • KARTHIKAYINI KRISHNASAMY Department of Nursing, University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia
  • ARULKUMARAN GOVINDARAJAN Department of Pharmaceutics, KMCH College of Pharmacy, Kovai Estate, Kalapatti, Coimbatore 641048, Tamil Nadu, India
  • AKILA SHANMUGASUNDARAM Assistant Professor, Department of Physical Education, Bharathiar University, Coimbatore 641046, Tamil Nadu, India


Migraine is a recurrent throbbing or pulsing headache with moderate to severe pain intensity. The pain is often one side of the head with nausea and weakness symptoms. Around 12 percent of Americans, 9 percent of Asians experiences migraine and the prevalence is highest among South Koreans (22.3%). The outcome of chronic migraine treatment can be quite disheartening, causing patients to feel out of options who have tried multiple treatments with no results. Poor efficacy, tolerability and safety of migraine preventive therapy in clinical practice lead to poor compliance and failure of therapy. The mean change in number or frequency of headache is considered as the outcome measure of migraine prevention therapy. Upon comparing all migraine prevention therapy, the Fremanezumab, Eptinezumab, Galcanezumab and Erenumab were considered as the front runner in controlling the severity and frequency of migraine. Among these drugs, Erenumab was most effective in controlling the frequency of migraine episodes as it produces more than 50 percent reduction in the mean number of monthly migraine days (MMD) over week 9-week 12. In addition to drug therapy, adequate rest, balanced diet, yoga and meditation will help patients to get rid of migraine severity. A multi-dimensional approach is essential for better control over migraine symptoms.

Keywords: Headache, Migraineurs, Nausea, Safety, Tolerability, Phonophobia


Download data is not yet available.


1. Bartleson JD, Cutrer FM. Migraine update-diagnosis and treatment. Minn Med 2010;93:36-41.
2. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev 2017;97:553-622.
3. Buse DC, Scher AI, Dodick DW, Reed ML, Fanning KM, Manack Adams A, et al. Impact of migraine on the family: perspectives of people with migraine and their spouse/domestic partner in the CaMEO study. Mayo Clin Proc 2016;91:596-611.
4. Ferrari MD, Klever RR, Terwindt GM, Ayata C, van den Maagdenberg AM. Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol 2015;14:65-80.
5. Goadsby PJ, Lipton RB, Ferrari MD. Migraine-current understanding and treatment. N Engl J Med 2002;346:257-70.
6. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007;68:343-9.
7. Steiner TJ, Stovner LJ, Vos T. GBD 2015: migraine is the third cause of disability in under 50s. J Headache Pain 2016;17:104.
8. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001;41:646-57.
9. Stewart WF, Shechter A, Rasmussen BK. Migraine prevalence. A review of population-based studies. Neurology 1994;44:S17-23.
10. Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol 2010;30:107-9.
11. Menon R. Women more prone to headaches: study. Deccan Herald. Available from: [Last accessed on 10 Feb 2020]
12. Steiner TJ, Stovner LJ, Birbeck GL. Migraine: the seventh disabler. Cephalalgia 2013;33:289-90.
13. Steiner TJ, Stovner LJ, Birbeck GL. Migraine: the seventh disabler. Headache 2013;53:227-9.
14. Steiner TJ, Stovner LJ, Birbeck GL. Migraine: the seventh disabler. J Headache Pain 2013;14:1.
15. Steiner TJ, Birbeck GL, Jensen RH, Katsarava Z, Stovner LJ, Martelletti P. Headache disorders are the third cause of disability worldwide. J Headache Pain 2015;16:58.
16. GBD 2013 Risk Factors Collaborators, Forouzanfar MH, Alexander L, Anderson HR, Bachman VF, Biryukov S, et al. Global, regional, and national comparative risk assessment of 79 behavioral, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386:2287-323.
17. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015:a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388:1545-602.
18. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211-59.
19. Chan KY, Vermeersch S, de Hoon J, Villalon CM, Maassenvandenbrink A. Potential mechanisms of prospective antimigraine drugs: a focus on vascular (side) effects. Pharmacol Ther 2011;129:332-51.
20. Charles A. The evolution of a migraine attack-a review of recent evidence. Headache 2013;53:413-9.
21. Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the United States: fig. and trends from government health studies. Headache 2018;58:496-505.
22. Deen M, Correnti E, Kamm K, Kelderman T, Papetti L, Rubio-Beltran E, et al. Blocking CGRP in migraine patients-a review of pros and cons. J Headache Pain. 2017;18:96.
23. Russo AF. Calcitonin gene-related peptide (CGRP): a new target for migraine. Annu Rev Pharmacol Toxicol 2015;55:533-52.
24. Uddman R, Edvinsson L, Ekman R, Kingman T, McCulloch J. Innervation of the feline cerebral vasculature by nerve fibers containing calcitonin gene-related peptide: trigeminal origin and co-existence with substance P. Neurosci Lett 1985;62:131-6.
25. Keller JT, Marfurt CF. Peptidergic and serotoninergic innervation of the rat dura mater. J Comp Neurol 1991;309:515-34.
26. Yeh J, Akinci A, Al Shaker M, Chang MH, Danilov A, Guillen R, et al. Monoclonal antibodies for chronic pain: a practical review of mechanisms and clinical applications. Mol Pain 2017;13:174480691774023.
27. Pardutz A, Schoenen J. NSAIDs in the acute treatment of migraine: a review of clinical and experimental data. Pharmaceuticals (Basel) 2010;3:1966-87.
28. Mekaj YH, Daci FT, Mekaj AY. New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism. Ther Clin Risk Manag 2015;11:1449-56.
29. Walter S, Alibhoy A, Escandon R, Bigal ME. Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide. MAbs 2014;6:871-8.
30. Lovati C, Giani L, Mariotti D, Alessandro C, Tabaee Damavandi P, Mariani C, et al. May migraine attack response to triptans be a predictor of the efficacy of Onabotulinum toxin-a prophylaxis? Neurol Sci 2018;39:153-4.
31. Peck KR, Johnson YL, Smitherman TA. Migraine. Handb Clin Neurol 2016;138:283-93.
32. Bell IM. Calcitonin gene-related peptide receptor antagonists: new therapeutic agents for migraine. J Med Chem 2014;57:7838-58.
33. Monteith TS, Goadsby PJ. Acute migraine therapy: new drugs and new approaches. Curr Treat Options Neurol 2010;13:1-14.
34. Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type a as a migraine preventive treatment. For the BOTOX migraine clinical research group. Headache 2000;40:445-50.
35. Melo Carrillo A, Strassman AM, Nir RR, Schain AJ, Noseda R, Stratton J, et al. Fremanezumab-a humanized monoclonal anti-CGRP antibody-inhibits thinly myelinated (A?) but not unmyelinated (C) meningeal nociceptors. J Neurosci 2017;37:10587-96.
36. Schwedt TJ. Chronic migraine. Br Med J 2014;348:g1416.
37. Monteith D, Collins EC, Vandermeulen C, Van Hecken A, Raddad E, Scherer JC, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the CGRP binding monoclonal antibody LY2951742 (Galcanezumab) in healthy volunteers. Front Pharmacol. 2017;8:740.
38. Bloudek LM, Stokes M, Buse DC, Wilcox TK, Lipton RB, Goadsby PJ, et al. Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS). J Headache Pain 2012;13:361-78.
39. Shi L, Lehto SG, Zhu DX, Sun H, Zhang J, Smith BP, et al. Pharmacologic characterization of AMG 334, a potent and selective human monoclonal antibody against the calcitonin gene-related peptide receptor. J Pharmacol Exp Ther 2016;356:223-31.
40. Hostetler ED, Joshi AD, Sanabria Bohorquez S, Fan H, Zeng Z, Purcell M, et al. In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer 11CMK-4232. J Pharmacol Exp Ther 2013;347:478-86.
41. Eftekhari S, Salvatore C, Johansson S, Chen TB, Zeng Z, Edvinsson L. Localization of CGRP, CGRP receptor, PACAP and glutamate in the trigeminal ganglion. Relation to the blood-brain barrier. Brain Res 2015;1600:93-109.
42. Vu T, Ma P, Chen JS, de Hoon J, Van Hecken A, Yan L, et al. Pharmacokinetic-pharmacodynamic relationship of erenumab (AMG 334) and capsaicin-induced dermal blood flow in healthy and migraine subjects. Pharm Res 2017;34:1784-95.
43. Hougaard A, Tfelt Hansen P. Review of dose-response curves for acute antimigraine drugs: triptans, 5-HT1F agonists and CGRP antagonists. Expert Opin Drug Metab Toxicol 2015;11:1409-18.
44. Schuster NM, Vollbracht S, Rapoport AM. Emerging treatments for primary headache disorders. Neurol Sci 2015;36:109-13.
45. De Hoon JN, Poppe KA, Thijssen HH, Struijker Boudier HA, Van Bortel LM. Dihydroergotamine: discrepancy between arterial, arteriolar and pharmacokinetic data. Br J Clin Pharmacol 2001;52:45-51.
46. Winner P, Dalessio D, Mathew N, Sadowsky C, Turkewitz L, Sheftell F, et al. Office-based treatment of acute migraine with dihydroergotamine mesylate. Headache 1993;33:471-5.
47. Evers S, Gralow I, Bauer B, Suhr B, Buchheister A, Husstedt I, et al. Sumatriptan and ergotamine overuse and drug-induced headache: a clinicoepidemiologic study. Clin Neuropharmacol 1999;22:201-6.
48. Freitag FG. Importance of botulinum toxin for the prevention of migraine. Expert Rev Neurother 2010;10:339-40.
49. Dodick WD, Silberstein DS, Bigal ME, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, et al. Effect of fremanezumab compared with placebo for prevention of episodic migraine-a randomized clinical trial. JAMA 2018;319:1999-2008.
50. Bigal ME, Edvinsson L, Rapoport AM, Lipton RB, Spierings EL, Diener HC, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol 2015;14:1091-100.
51. Cohen JM, Dodick DW, Yang R, Newman LC, Li T, Aycardi E, et al. Fremanezumab as an add-on treatment for patients treated with other migraine preventive medicines. Headache 2017;57:1375-84.
52. Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomized, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol 2014;13:1100-7.
53. Dodick DW, Lipton RB, Silberstein S, Goadsby PJ, Biondi D, Hirman J, et al. Eptinezumab for prevention of chronic migraine: a randomized phase 2b clinical trial. Cephalalgia 2019;39:1075-85.
54. Pellesi L, Guerzoni S, Pini LA. Spotlight on anti-CGRP monoclonal antibodies in migraine: the clinical evidence to date. Clin Pharmacol Drug Dev 2017;6:534-47.
55. Schuster NM, Rapoport AM. New strategies for the treatment and prevention of primary headache disorders. Nat Rev Neurol 2016;12:635-50.
56. Camporeale A, Kudrow D, Sides R, Wang S, Van Dycke A, Selzler KJ, et al. A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine. BMC Neurol 2018;18:188.
57. Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim BK, Yang JY. Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia 2018;38:1442-54.
58. Forderreuther S, Zhang Q, Stauffer VL, Aurora SK, Lainez MJA. Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled evolve-1, evolve-2, and regain studies. J Headache Pain 2018;19:121.
59. Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri Minet M, Osipova V, et al. ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia 2018;38:1026-37.
60. Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016;15:382-90.
61. Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med 2017;377:2123-32.
62. Reuter U, Goadsby PJ, Lanteri Minet M, Wen S, Hours Zesiger P, Ferrari M, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet 2018;392:2280-7.
63. Tepper S, Ashina M, Reuter U, Brandes JL, Dolezil D, Silberstein S, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomized, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017;16:425-34.
64. Silberstein SD, McCrory DC. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache 2003;43:144-66.
65. Levin M, Silberstein SD, Gilbert R, Lucas S, Munsie L, Garrelts A, et al. Basic considerations for the use of monoclonal antibodies in migraine. Headache 2018;58:1689-96.
66. Ho TW, Connor KM, Zhang Y, Pearlman E, Koppenhaver J, Fan X, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology 2014;83:958-66.
67. Aimovig (erenumab?aooe) injection (package insert). Thousand Oaks, CA: Amgen Inc; 2018.
68. Skljarevski V, Oakes TM, Zhang Q, Ferguson MB, Martinez J, Camporeale A, et al. Effect of different doses of galcanezumab vs placebo for episodic migraine prevention: a randomized clinical trial. JAMA Neurol 2018;75:187-93.
196 Views | 265 Downloads
How to Cite
SIVANANDY, P., A. N. ROSMAN, A. D. SHAPHERI, T. T. CHEW, N. J. X. LAU, M. Z. Y. YEONG, M. ONG, B. M. U. H. MEETOOA, E. NG, K. KRISHNASAMY, A. GOVINDARAJAN, and A. SHANMUGASUNDARAM. “COMPARISON OF EFFICACY AND SAFETY OF NEWER DRUGS APPROVED FOR THE TREATMENT OF MIGRAINE DISORDER: A REVIEW”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 12, no. 7, May 2020, pp. 1-9, doi:10.22159/ijpps.2020v12i7.37440.
Review Article(s)