Evaluation of propranolol, flunarizine and divalproex sodium in prophylaxis of migraine


  • Majid F. Bhat Department of Pharmacology, Maharishi Markandeshwar Medical College & Hospital, Kumarhatti, Solan 173229, India
  • Harpreet S. Sidhu Department of Pharmacology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala 133207, India
  • Manoj Goyal Department of Pharmacology, N.C Medical College & Hospital, Panipat, Haryana 132107, India




Divalproex sodium, Flunarizine, Migraine, Prophylaxis, Propranolol


Background: Preventive treatment has an important role in the management of migraine. Propranolol and flunarizine have been used for more than two decades while, open-label, controlled studies suggest divalproex sodium may also be efficacious for migraine prevention. The objective of the study to compare efficacy and safety of propranolol, flunarizine and divalproex sodium in patients for migraine prophylaxis.

Methods: Following approval from IEC a 12-week randomized, open, comparative study was carried out at the outpatient department of Medicine. Patients between 18 to 65 years, with history of 3 to 12 migraines a month (IHS) for six months were included. Patients were divided into three groups of 30 patients to receive - propranolol 20 to 160mg/day; flunarizine 5 to 10mg/day or divalproex sodium 250 to 750mg/day, for three months.

Results: Total 90/116 patients completed the study. No significant differences were found between the groups with regards to mean age or other baseline migraine features. All the drugs significantly decreased the frequency, duration and severity of migraine (P<0.001). There is no statistically significant difference between propranolol, flunarizine and divalproex sodium for any of the efficacy parameters. All the three treatments were well-tolerated and safe.

Conclusions: All the three study drugs were equally effective with an acceptable tolerability profile, Divalproex sodium group showed more side effects, none of which were serious. However, further studies with larger number of patients and longer duration of treatment are recommended.


Critchley M. Migraine: From Cappadocia to Queen Square. Background to Migraine In: Smith R, ed. London: Heinemann. 1967;1:28-39.

Mathew NT. Migraine. In: Evans RW, Mathew NT. Handbook of Headache. Second Edition. Lippincott Williams & Wilkins; 2005:28-55.

Silberstein SD. Preventive migraine treatment. Neurol Clin. 2009;27(2):429-43.

Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd Edition (beta version). Cephalgia. 2013;33:629-808.

Wang SJ, Chung CS, Chankrachang S, Ravishankar K, Merican JS, Salazaret G. Migraine disability awareness campaign in Asia: migraine assessment for prophylaxis. Headache. 2008;48;1356-65.

Silberstein SD. In: Taylor & Francis eds. Headache in clinical practice, 2nd Ed; 2002.

Migraine RK. The New Understanding. Supplement of JAPI. Apr. 2010;58:30-3.

Deleu D, Hanssens Y. Guidelines for the prevention of migraine. Neurosciences. 2000;5(1):7-12.

D‟Amico D, Stewart JT, Prophylaxis of migraine: General principles and patient acceptance. Neuropsychiatric Disease and Treatment. 2008;4(6):1155-67.

Silberstein SD. US Headache Consortium Practice parameter: evidence based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754-62.

Evers S. European Federation of Neurological Societies. EFNS guideline on the drug treatment of migraine-revised report of an EFNS task force. Eur J Neurol. 2009;16:968-81.

Lipton RB, Bigal ME, Diamond M, Freitag F. AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-9.

Vongvaivanich K. Update on Migraine Prophylaxis: Things that can help your migraine patients. The Bangkok Medical Journal. 2013 Feb;5:50-60.

Ecsei LV, Majlath Z, Szok D, Csati A, Tajti J. Drug safety and tolerability in prophylactic migraine treatment. Expert Opin. Drug Saf. 2015;14(5):1-15.

Weatherall MW. Drug therapy in headache. Clinical Medicine. 2015;15(3):273-9.

Russell MB, Rasmussen BK, Brennum J. Presentation of a new instrument: the diagnostic headache diary. Cephalalgia. 1992;12:369-74.

Leonardi M, Steiner TJ, Scher AT, Lipton RB. The global burden of migraine: measuring disability in headache disorders with WHO Classification of Functioning, Disability and Health (ICF). J. Headache Pain. 2005;6(6):429-40.

Linde K, Rossnagel K. Propranolol for migraine prophy- laxis. Cochrane Database Syst Rev. 2004;CD003225.

Linde M, Mulleners WM, Chronicle EP, McCrory DC. Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews. 2013;6:CD010611.

Bostani A, Rajabi A, Moradian N. The effects of cinnarizine versus sodium valproate in migraine prophylaxis. Int J Neurosci. 2013;123(7):487-93.

Jackson JL, Cogbill E, Santana-Davila R, Eldredge C, Collier W, Gradall A, et al. A comparative effectiveness meta-analysis of drugs for the prophylaxis of migraine headache. PloS one. 2015 Jul 14;10(7):e0130733.

Taylor FR. Weight change associated with the use of migraine preventive medications. Clinical therapeutics. 2008 Jun 30;30(6):1069-80.




How to Cite

Bhat, M. F., Sidhu, H. S., & Goyal, M. (2017). Evaluation of propranolol, flunarizine and divalproex sodium in prophylaxis of migraine. International Journal of Basic & Clinical Pharmacology, 6(10), 2463–2469. https://doi.org/10.18203/2319-2003.ijbcp20174377



Original Research Articles