Efficacy of Haloperidol vs. Metoclopramide for Treatment of Acute Headaches and Migraines in the Emergency Department

Study Overview
=================
Brief Summary
-----------------
Metoclopramide (Reglan) is a common agent used for relief of headaches in the emergency department (ED).In this study the investigators seek to explore another option for treatment of headaches in the ED, one that may be more efficacious and efficient. Haloperidol (Haldol), a butyrophenone class of medication, is thought to act by affecting the dopamine 2 receptor in the brain. By exploring haloperidol as an option for treatment, the investigators hope to discover a more efficient and effective medication for the treatment of non-traumatic headaches, thereby decreasing a patient's length of stay in the department and decreasing the rate of return visits for continued discomfort from the same headache. This study could lead to the increased usage of haloperidol as a first line agent in the treatment of prolonged headaches presenting to the ED.

Detailed Description
-----------------
At this time, choice of medications for the treatment of headaches in the ED is still based on personal and patient preferences because no properly constructed trials have been carried out that would allow identification of a superior agent. Metoclopramide (Reglan) is a common agent used for relief of headaches in the ED. Uncontrolled studies have shown successful relief of migraine with metoclopramide of 75%. Further studies have reported success rate of 67% with IV metoclopramide. In this study the investigators seek to explore another option for treatment of headaches in the ED, one that may be more efficacious and efficient. Haloperidol (Haldol), a butyrophenone class of medication, is thought to act by affecting the dopamine 2 receptor in the brain. These receptors are relatively abundant in the brainstem nuclei and sympathetic ganglia and nerves, through which they may regulate autonomic visceral, gastrointestinal, and hemodynamic responses frequently associated with migraine. One study, demonstrated that 4 out of 5 patients felt significant relief in pain intensity with the use of haloperidol, even when other medications had failed. Relapses were rare, and several patients reported that haloperidol interrupted the prolonged, intractable migraine spiral they had suffered for days. Furthermore, a case series of six cases of migraine treated with 5mg of haloperidol IV after a 500 to 1000ml bolus of IV fluids reported complete or substantial relief within 25 to 65 minutes and side effects were reported as minimal. The investigators hypothesize that Haloperidol is more efficacious than metoclopramide in the treatment of an acute headache or migraine in the ED in regard to a self-reported pain rating scale (Numeric Pain Intensity Scale), need for additional medication, emergency department return rates, and resolution of symptoms.

Official Title
-----------------
Investigating the Efficacy of Using Haloperidol vs. Metoclopramide for Treatment of Acute Headaches and Migraines in the Emergency Department: A Prospective Randomized Clinical Trial

Conditions
-----------------
Headache, Migraine

Intervention / Treatment
-----------------
* Drug: Metoclopramide
* Drug: Haloperidol
* Other: Normal Saline
* Drug: Diphenhydramine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who present with a headache or migraine with onset less than or equal to 72 hours Exclusion Criteria: Known pregnancy Breast-feeding women Known history of arrhythmias or QT prolongation (450 ms) Known adverse effects to haloperidol, diphenhydramine (Benadryl) or metoclopramide Subarachnoid hemorrhage Headaches caused by trauma, meningitis Congestive heart failure Parkinson's Disease Dementia Pheochromocytoma History of glaucoma History of seizures Non-English speaking patients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metoclopramide (Reglan)<br>Patients will receive 10 mg of intravenous (IV) metoclopramide following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. | Drug: Metoclopramide<br>* Patients receive 10 mg of intravenous (IV) metoclopramide.<br>* Other names: Reglan;Other: Normal Saline<br>* All patients receive a 1-liter bolus of normal saline (NS)<br>Drug: Diphenhydramine<br>* All patients receive 25 mg of intravenous (IV) diphenhydramine.<br>* Other names: Benadryl;|
| Experimental: Haloperidol (Haldol)<br>Patients will receive 2.5 mg of intravenous (IV) haloperidol following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. | Drug: Haloperidol<br>* Patients receive 2.5 mg of IV haloperidol.<br>* Other names: Haldol;Other: Normal Saline<br>* All patients receive a 1-liter bolus of normal saline (NS)<br>Drug: Diphenhydramine<br>* All patients receive 25 mg of intravenous (IV) diphenhydramine.<br>* Other names: Benadryl;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain Score According to the Numeric Pain Intensity Scale | Numeric Pain Intensity scale is a standard rating tool for pain, ranging from 0-10, with 0=no pain and 10=worst pain imaginable. | Change from baseline (prior to treatment) to 1 hour post treatment (1 hour) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for Additional Medications Used in the Emergency Department (ED) | Need for additional medications in the ED will be evaluated via chart review at 48 hours post discharge | 48 hours post discharge | 
| Occurrence of Patient Return to the Emergency Department (ED) or Other Healthcare Provider for Headache/Migraine Within 48 Hours of ED Discharge | Occurrence of patient return to the ED or other healthcare provider for headache/migraine within 48 hours of ED discharge will be evaluated via chart review at 48 hours post discharge | 48 hours post discharge | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metoclopramide (Reglan), Haloperidol (Haldol)