Preventive effect of citalopram on migraine headaches: a double-blinded randomized clinical trial

Document Type : Research Paper


1 Student of Medicine, Shahed University, Tehran, Iran

2 Assistant Professor of Neurosurgery, Shahed University, Tehran, Iran

3 Associate professor of social medicine Shahed University

4 Medical Students Research Committee, Shahed University, Tehran, Iran

5 Neurophysiology Research Center, Shahed University, Tehran, Iran

6 Assistant Professor of Pediatrics, Faculty of Medicine, Shahed University, Tehran, Iran

7 Internal Medicine Department, Faculty of Medicine, Shahed University, Tehran, Iran

8 Assistant Professor of Psychiatry, Shahed University, Tehran, Iran

9 Associate Professor of Neurology, Neurophysiology Research Center, Shahed University, Tehran, Iran


Objective: The aim of this study was to evaluate the effect of citalopram on the prevention of migraine headaches as compared to placebo.
Materials and Methods: This double-blind randomized clinical trial was conducted on patients diagnosed with migraine headaches based on the guidelines of the International Headache Society. 226 patients who met inclusion criteria were randomly allocated to two control and intervention groups. The treatment group was treated with citalopram 30 mg daily for two months and the control group was given placebo the same amount as the treatment group. All the patients were assessed at the beginning of the trial and after 1 month and 2 months and the frequency, severity and duration of their headaches were documented using the Visual Analogue Scale (VAS) and Behavioral Rating Scale (BRS-6). Data were analyzed using SPSS v.16 software.   
Results: Even though initially there was no statistically significant difference between the two groups regarding the severity, duration and frequency of episodes of migraine (P>0.05), the same parameters had drastic changes after the first and second months of treatment and the differences between the citalopram and placebo group regarding severity, duration and frequency of migraine episodes were statistically significant (P<0.05).
Conclusion: The outcome of this experiment showed that citalopram, a serotonin uptake inhibitor (SSRI), possibly through a serotonin-lowering mechanism, results in less exposure of the CNS to this agent, leading to less frequent, less severe and shorter migraine episodes. This medication appears to be useful as a preventive drug used to treat and maintain episodes of migraine headaches, especially in individuals suffering from both migraine headaches and clinical depression.  



    1. Mohammadianinejad, S., Madjdinasab, N., Ghobadi, S., Tarahomi, S., Kashipazha, D., Rafie, S., Rahmanian, Z., Reza Shakeri5, S. A Clinical Trial for Evaluating the Efficacy of Magnesium in Migraine Prophylaxis. Jundishapur Scientific Medical Journal 2014; 13(1): 43-50.
    2. Hansen JM, Goadsby PJ, Charles AC. Variability of clinical features in attacks of migraine with aura. Cephalalgia 2016;36(3):216-24.
    3. Hansen JM, Lipton RB, Dodick DW, Silberstein SD, Saper JR, Aurora SK, et al. Migraine headache is present in the aura phase: a prospective study. Neurology 2012;79(20):2044-9.
    4. Puledda F, Messina R, Goadsby PJ. An update on migraine: current understanding and future directions. Journal of Neurology 2017;264(9):2031-2039.
    5. Hansen RD, Christensen AF, Olesen J. Family studies to find rare high risk variants in migraine. Journal of Headache and Pain 2017;18(1):32.
    6. Younger DS. Epidemiology of Migraine. Neurologic Clinics 2016;34(4):849-861.
    7. Raskin NH, Green MG. Headache. In: Rowland Lp, Editor. Merritts Neurology. 11th ed . Philadelphia; Lippincott Williams and Wilkins; 2005. P. 46-8.
    8. Rabiee B, Zeinoddini A, Kordi R, Yunesian M, Mohammadinejad P, Mansournia MA. The Epidemiology of Migraine Headache in General Population of Tehran, Iran. Neuroepidemiology. 2016;46(1):9-13.
    9. Cohen JM, Bigal ME, Newman LC. Migraine and vestibular symptoms--identifying clinical features that predict "vestibular migraine". Headache 2011;51:1393-97.
    10. Manzoni GC, Torelli P. Headache screening and diagnosis. Neurological Sciences 2004;25 3:S255-57.
    11. Shahmirzadi S, Mohsenzadeh Kermani N. Efficacy of venlafaxine versus nortriptyline for migraine prophylaxis. Medical Sciences 2016; 26 (2) :95-98.
    12. DeConde AS, Mace JC, Smith TL. The impact of comorbid migraine on quality-of-life outcomes after endoscopic sinus surgery. Laryngoscope 2014;124:1750-55.
    13. Stulin ID, Kunel'skaia NL, Tardov MV, Baĭbakova EV, Chugunova MA, Zaoeva ZO, et al. Basilar type migraine: clinical features, differential diagnosis. Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova 2014;114:4-8.
    14. Wang SJ, Chen PK, Fuh JL. Comorbidities of migraine. Frontiers in Neurology 2010;1:16.
    15. Holroyd KA, Drew JB, Cottrell CK, Romanek KM, Heh V. Impaired functioning and quality of life in severe migraine: the role of catastrophizing and associated symptoms. Cephalalgia 2007;27:1156-65.
    16. Garza I, Swanson JW. Prophylaxis of migraine. Neuropsychiatric Disease and treatment 2006;2(3):281-91.
    17. Bartolini M, Silvestrini M, Taffi R, Lanciotti C, Luconi R, Capecci M, et al. Efficacy of topiramate and valproate in chronic migraine. Clinical Neuropharmacology 2005; 28(6):277-9.
    18. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2163–96.
    19. Leonardi M, Steiner TJ, Scher AT, Lipton RB. The global burden of migraine: measuring disability in headache disorders with WHO’s Classification of Functioning, Disability and Health (ICF). Journal of Headache and Pain 2005; 6:429–40.
    20. Abbasi M, Nabavi SM, Fereshtehnejad SM, Jou NZ, Ansari I, Shayegannejad V, et al. Multiple sclerosis and environmental risk factors: a case-control study in Iran. Neurological Science 2017 Nov; 38(11):1941-1951.
    21. Zhang Y, Parikh A, Qian S. Migraine and stroke. Stroke and Vascular Neurology 2017; 2(3):160-167.
    22. Abbasi M, Nabavi SM, Fereshtehnejad SM, Ansari I, Zerafatjou N, Shayegannejad V, et al. Risk factors of Multiple sclerosis and their Relation with Disease Severity: A Cross-sectional Study from Iran. Archives of Iranian Medicine 2016; 19(12):852-860.
    23. Ertas M, Baykan B, Orhan EK, Zarifoglu M, Karli N, Saip S, et al. One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults. Journal of Headache and Pain 2012;13(2):147–57.
    24. Afshinmajd S, Davati A, Akbari F. The effects of body mass index on the treatment of the patients with migraine headaches. Iranian Journal of Neurology 2011; 10(3-4):35-38.
    25. Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. Journal of Neuroscience 2015; 35(17):6619-29.
    26. Hamel E. Serotonin and migraine: biology and clinical implications. Cephalalgia. 2007; 27(11):1293-300.
    27. Banzi R, Cusi C, Randazzo C, Sterzi R, Tedesco D, Moja L. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension-type headache in adults. Cochrane Database of Systematic Review 2015; 2015(5):CD011681.
    28. Cipriani A, Purgato M, Furukawa TA, Trespidi C, Imperadore G, Signoretti A, et al. Citalopram versus other anti-depressive agents for depression. Cochrane Database of Systematic Review. 2012; 7(7):CD006534.
    29. Ittner KP. Pharmacotherapy: migraine and depression. Therapy with sumatripten and citalopram: perioperative anaesthesiological risk assessment. Anasthesiol Intensivmed Notfallmed Schmerzther 2006; 41(7-8):464-5.
    30. Rampello L, Alvano A, Chiechio S, Malaguarnera M, Raffaele R, Vecchio I, et al. Evaluation of the prophylactic efficacy of amitriptyline and citalopram, alone or in combination, in patients with comorbidity of depression, migraine, and tension-type headache. Neuropsychobiology 2004; 50(4):322-8.