Clinical Neurology and Neurosurgery 112 (2010) 463–466 Contents lists available at ScienceDirect Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro Botulinum toxin type A versus amitriptyline for the treatment of chronic daily migraine Elza Magalhães, Carla Menezes, Mauricio Cardeal, Ailton Melo ∗ Division of Neurology and Epidemiology, Federal University of Bahia, Av Reitor Miguel Calmon, s/n, Salvador, Bahia, Brazil article info Article history: Received 28 April 2009 Received in revised form 21 January 2010 Accepted 7 February 2010 Available online 18 April 2010 Keywords: Chronic migraine Amitriptyline Botulinum toxin abstract Objective: To compare the effects of botulinum toxin type A with those of amitriptyline on the treatment of chronic daily migraines. Methods: Chronic migraine sufferers were randomized into two groups and treated with 25 or 50 mg/day of amitriptyline or 250 U of botulinum toxin type A. A reduction of at least 50% in the number of pain episodes, in the intensity of pain, and in the number of drug doses for pain and reports of improvement by the patient or by the examiner were the main endpoints. Results: Seventy-two subjects were enrolled in the study. A reduction of at least 50% in the number of days of pain was recorded in 67.8% of the patients in the BTX-A group and 72% (n = 23) of the patients in the AM group (p = 0.78; RR = 0.94; CI = 0.11–8). The reduction in the intensity of pain, as assessed using the visual analogical scale, was 50% in the BXT-A group and 55.6% in the AM group (p = 0.79; RR = 1.11; CI = 0.32–3.8). The reduction in the number of pain drug doses was 77% for the toxin group and 71% for the amitriptyline group (p = 0.76; RR = 0.92; CI = 0.45–1.88). Conclusions: Botulinum toxin type A was as effective as amitriptyline for the prophylactic treatment of chronic daily migraines. © 2010 Elsevier B.V. All rights reserved. 1. Introduction According to the International Classification of Headache Dis- orders, 2nd Edition (ICHD-II), chronic daily migraine is defined as migraines that occur more than 15 days monthly for three consec- utive months [1]. The treatment of chronic daily migraine (CDM) with a variety of drugs that act to modulate pain threshold has been explored. Amitriptyline (AM) has been one of the most commonly used tricyclic antidepressants for the treatment of migraines, since the beginning of the 1970s. Studies have documented the efficacy rates for AM, ranging from 50 to 80% [2–5]. Despite the availability of various pharmacological alternatives as prophylactic agents against migraines, pain control is incon- sistent for these alternatives, and a number of patients do not respond to these substances [6]. Nonetheless, increasing knowl- edge about the pathophysiology of migraines has contributed to an improvement in its treatment. The trigeminal sensitive fibers that depart from Gasser’s ganglion contain neurotransmitters such Abbreviations: AM, amitriptyline; BTX-A, botulinum toxin type A; CDM, chronic daily migraine; IHS, Headache international society; ICHD-II, International Classifi- cation of Headache Disorders, 2nd Edition; SP, substance P; VAS, Visual analogical scale; CGRP, calcitonin gene-related peptide. ∗ Corresponding author. Tel.: +55 71 32476982; fax: +55 71 32476982. E-mail address: asm@ufba.br (A. Melo). as substance P (SP) and calcitonin gene-related peptide (CGRP) and are considered important in the physiopathology of migraines [7,8]. Experimental studies have demonstrated that the impulse from the trigeminal nerve induces dilation of the meningeal vessels and an outflow of plasma. This dilation and plasma outflow and the associated release of neurotransmitters as SP and CGRP, which unleash the neurogenic inflammation, are considered the main con- tributors to the occurrence of migraines [9,10]. Current research and clinical treatment has focused on the inhibition of CGRP through the action of new antagonists drugs for the treatment of CDM [11]. Reviewers describe relevant mechanisms of action of Botulinum toxin type A (BTX-A) and how the analgesic effects of this drugs occur through the blockade of SP, glutamate and CGRP [12]. Previous studies demonstrate that BTX-A can directly decrease the amount of CGRP released from trigeminal neurons. The results suggest that the effectiveness of BTX-A in the treat- ment of migraines may be due, in part, to its ability to repress CGRP release from activated sensory neurons [13]. Experimen- tal studies in rats have provided evidence for axonal transport and the central origin of the antinociceptive effect of BTX-A [14]. These studies demonstrate that both the unilateral subcu- taneous application of BTX-A (5 U/kg) and the injection of BTX-A into the proximal part of a distally cut sciatic nerve diminish pain. 0303-8467/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2010.02.004