Intravenous metoclopramide versus dexketoprofen trometamol versus metoclopramide+ dexketoprofen trometamol in acute migraine attack in the emergency department: A randomized double-blind controlled trial

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Abstract

Study objective

The objective of this study was to determine the analgesic efficacy and safety of intravenous, single-dose metoclopramide versus dexketoprofen trometamol versus metoclopramide+ dexketoprofen trometamol in patients presenting with acute migraine attack to the emergency department (ED).

Methods

This single-center, randomized, double-blind study was conducted in a tertiary care ED. Eligible patients met the migraine criteria of the International Headache Society were randomized to receive 10 mg intravenous metoclopramide, 50 mg intravenous dexketoprofen trometamol, or 50 mg dexketoprofen trometamol +10 mg metoclopramide. Visual analogue scale (VAS) was used for pain measurement at baseline, after 15 and 30 min. The primary outcome measure was the changes in the VAS scores at the 15th and 30th minutes of treatment. The secondary outcome measures were the presence of adverse effects and the requirement of rescue medicine.

Results

Patients (n = 150) were randomized into 3 groups with similar VAS scores at baseline. While there was no significant difference between metoclopramide and dexketoprofen trometamol in reducing pain at the 15th and 30th minute (p = 0.618 and p = 0.862, respectively) and between metoclopramide and metoclopramide + dexketoprofen trometamol at the 15th minute (p = 0.074), metoclopramide + dexketoprofen trometamol was superior to both metoclopramide [mean difference: −13.2 mm (95% CI −23.1 to −3.3)] and dexketoprofen trometamol [mean difference: −11.02 mm (95% CI −20.9 to −1.1)] at the 30th min (p = 0.006 and p = 0.025 respectively). The rescue drug was required by 3 patients (6%) were in metoclopramide group, 4 patients (8%) in dexketoprofen trometamol group and one patient (2%) in the metoclopramide + dexketoprofen trometamol group. No side effects were observed in subjects in three treatment groups.

Conclusion

No significant difference in VAS was found between three treatment groups at the 15th minute, but metoclopramide + dexketoprofen trometamol was superior to both metoclopramide and dexketoprofen trometamol at the 30th min.

Introduction

Migraine is a disorder of the central nervous system characterized by a moderate or severe headache, which is generally associated with nausea and/or sensitivity to light and sound, interfering with daily activities [1]. Migraine is frequently seen, and it is the third most common disease in the world. Globally, it is the third leading cause of the obstruction of daily activities in men and women under the age of 50. It leads to a significant decrease in work efficiency and an increase in health-related and indirect costs. Not surprisingly, given the nature and severity of symptoms, acute headache is one of the most common reasons for presentation to the emergency department (ED), accounting for 2–3% of all emergency visits. Classically, migraine occurs in the form of severe, throbbing headaches that are episodic and last for four to 72 h [2,3].

The pharmacological treatment of migraine may be acute or preventive, while severe migraine patients often require both approaches. Preventive treatments are used to reduce the frequency, duration or severity of attacks. In addition to preventive treatments, choosing the appropriate medicine for acute migraine in ED contributes to improving the quality of life of patients and reducing health costs [4].

Migraine-type headache is frequently seen in ED and results in the not only loss of workforce and increased costs within the department but also interferes with patients' daily and work-related activities with financial repercussions [5].

It has been shown that the prescription of highly addictive drugs, such as opioids in migraine headaches results in both the use of higher doses of medication and more frequent visits to ED. Therefore, migraine attacks (symptomatic) are now often treated with non-steroidal anti-inflammatory drugs (NSAIDs) or simple analgesics, such as acetaminophen, as well as triptans, antiemetics, and dihydroergotamine, which is less commonly used. The pharmacological approach to migraine is mainly determined by patient-specific factors, such as the severity of attacks, presence of associated nausea and vomiting, treatment environment, and the patient's sensitivity to the drug [6,7]. However, uncertainties remain concerning the comparative efficacy of the drugs indicated for the treatment of acute migraine attacks. Recent meta-analyses and systematic reviews highlight the need for better alone or combined drug therapies for the treatment of these attacks [8].

There have been studies that showed the clinical efficacy of alone dexketoprofen [9,10] and alone metoclopramide [11,12] in acute migraine attacks. In recent review articles, the usability of the combination of paracetamol [13], ibuprofen from NSAIDs [14], and aspirin [15] with metoclopramide has evaluated in migraine headaches in adults.

Depending on the pharmacokinetic properties of dexketoprofen and metoclopramide, the rationale for combining two drugs is that metoclopramide with prokinetic effect increases the effectiveness of the treatment by increasing the gastrointestinal absorption of triptans and NSAIDs [16]. Also, nausea and vomiting are occurred clinically high frequently in patients during migraine attacks. In its treatment, it recommended combining an antiemetic with NSAIDs before nausea and vomiting begin. [17]

There is no randomized controlled trial using a combination of dexketoprofen and metoclopramide. We aimed to compare the effectiveness of alone and combined use of intravenous metoclopramide and intravenous dexketoprofen trometamol in patients presenting to ED with acute migraine pain.

Section snippets

Study design and setting

This study was designed as a prospective, double-blind, randomized controlled trial and was planned as a superiority trial.

This study was conducted between 03/07/2019 and 03/01/2020 in the ED of Adiyaman University Training and Research Hospital, which receives an average of 25,000 applications per month. The study was approved by the ethics committee of the hospital (No: 2019-6-1) and the Turkish Medicines and Medical Devices Agency (No: 66175679-514.04.01). Written consent was obtained from

Characteristics of study subjects

During the study period, 271 patients met the eligibility criteria and 121 patients were excluded from the study. As a result, 150 patients (55%) were randomized into the three treatment groups: metoclopramide (n = 50), dexketoprofen trometamol (n = 50), or dexketoprofen trometamol + metoclopramide (n = 50). The details of these patients are given in Fig. 1. Of the patients included in the study, 107 (71.3%) were female and 43 (28.7%) were male. The mean age of the patients was

Discussion

This is the first randomized controlled trial comparing alone and combined use of metoclopramide and dexketoprofen trometamol in the treatment of migraine headaches. Many studies have investigated the use of dexketoprofen trometamol in this type of headache. While the use of dexketoprofen trometamol alone and in combination with triptans was compared to placebo and other analgesics, and most studies found alone and combined use to be effective in the relief of migraine headaches [10,21], a few

CRediT authorship contribution statement

E. Yavuz: Conceptualization, Methodology, Visualization, Software, Investigation, Data curation,Writing - original draft U. Gulacti: Conceptualization, Methodology, Visualization, Software, Investigation, Formal analysis, Writing - original draft. U. Lok: Conceptualization, Methodology, Writing - review & editing, Supervision. K. Turgut: Conceptualization, Methodology, Visualization, Software, Investigation, Data curation.

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