We performed a systematic review and Bayesian network meta-analysis to determine which pharmacologic therapies are relatively more effective and safer for migraine in adult patients who present to the emergency department (ED).

We searched MEDLINE, Embase, and Web of Science from inception to February 9, 2024. Eligible studies were randomized controlled trials that enrolled adult participants presenting to ED with migraine and compared one pharmacologic therapy to another or placebo. Outcomes were as follows: 1) adequate pain relief at 2 hours, 2) change in pain intensity at 1 hour, 3) need for rescue drug at 2 hours, and 4) significant adverse reaction. We extracted data according to PRISMA-network meta-analysis and appraised trials using Cochrane RoB 2. For dichotomous outcomes, we performed Bayesian network meta-analysis to calculate odds ratios with 95% credible intervals; for continuous outcomes, we performed frequentist network meta-analysis to calculate mean differences with 95% confidence intervals. We assessed confidence using Confidence in Network Meta-analysis. We used Surface under the cumulative ranking curve (SUCRA) to rank agents.

Chlorpromazine intravenous (IV)/intramuscular (IM) (SUCRA=87.3%) was most likely to be superior for "adequate pain relief at 2 hours" (24 trials; n=2,361); metoclopramide IV-ibuprofen IV (SUCRA=94.6%) was most likely to be superior for "need for rescue drug" (not needing rescue drug) at 2 hours (27 trials; n=2,942); dexamethasone IV (SUCRA=79.5%) was most likely to be superior for "significant adverse reaction" (not causing adverse reaction) (22 trials; n=2,450). The network for change in pain intensity demonstrated statistically significant incoherence at the overall level. Confidence in network meta-analysis estimates (certainty of evidence) varied and was mostly "low" or "very low," limiting the validity of the probabilistic analyses.

According to Bayesian network meta-analysis, ibuprofen IV is definitely among the least effective for adequate pain relief; chlorpromazine IV/IM is definitely among the most effective; valproate IV is definitely among the least effective, and ketorolac IV/IM is possibly among the least effective as single agents. The relative safety of the pharmacologic therapies cannot be determined with sufficient certainty.

To compare the effectiveness of parenteral agents to reduce relapse in patients with acute migraine and identify factors that predict relapse.

Following discharge from emergency settings, many patients with acute migraine will experience a relapse in pain; severe relapses may result in re-visits to emergency settings.

A comprehensive literature search, updated to 2023, was conducted to identify randomized controlled trials assessing the effectiveness of parenteral agents on relapse outcomes in patients with acute migraine discharged from emergency settings. Two independent reviewers completed study selection, quality assessment, and data extraction. A traditional meta-analysis compared parenteral corticosteroids to placebo; a frequentist network analysis assessed direct and indirect comparisons. Results are reported as risk ratios (RRs) and 95% confidence intervals (CIs). The review protocol was registered with the International Prospective Register of Systematic Reviews (identifier: CRD42018099493).

From 8949 citations, a total of 53 unique studies were included involving 6167 patients. Most studies had a high or unclear risk of bias. Corticosteroids significantly reduced relapses compared to placebo (RR 0.67, 95% CI 0.52-0.88; I2 = 0%). Patients receiving lidocaine (RR 0.10, 95% CI 0.01-0.82), sedatives/hypnotics (RR 0.33, 95% CI 0.14-0.75), ergot agents (RR 0.44, 95% CI 0.25-0.75), neuroleptics (RR 0.47, 95% CI 0.31-0.71), opioids (RR 0.58; 95% CI 0.35-0.94), or corticosteroids (RR 0.64, 95% CI 0.47-0.86) were significantly less likely to relapse. Lidocaine (RR 0.09, 95% CI 0.01-0.71), combination therapy (RR 0.12, 95% CI 0.02-0.74), or adding corticosteroids (RR 0.61, 95% CI 0.44-0.84) were more likely to reduce severe relapses. Longer duration of headache and residual pain at discharge were significantly associated with higher relapses.

Corticosteroids remain the recommended first-line option to reduce relapse outcomes. Some parenteral agents typically provided for pain relief including ergot agents, neuroleptics, or combination therapy may effectively reduce relapse; however, opioids are not recommended due to safety concerns. Additional research is needed for some lesser studied, albeit promising, agents including lidocaine and propofol. Effective pain control in emergency settings prior to discharge and duration of headache may play a role in the success of such treatments and further investigations could provide further insight regarding how and why some parenteral agents are effective in mitigating relapse events.

To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine.

Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear.

Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096).

A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics.

Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.

Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs.

We searched online databases like PubMed, Cochrane Library, Scopus, and Web of Science till June 2022 for RCTs that compared metoclopramide alone with placebo or active drugs. The main outcomes were the mean change in headache score and complete headache relief. The secondary outcomes were the rescue medications need, side effects, nausea and recurrence rate. We qualitatively reviewed the outcomes. Then, we performed the network meta-analyses (NMAs) when it was possible. which were done by the Frequentist method using the MetaInsight online software.

Sixteen studies were included with a total of 1934 patients: 826 received metoclopramide, 302 received placebo, and 806 received other active drugs. Metoclopramide was effective in reducing headache outcomes even for 24 h. The intravenous route was the most chosen route in the included studies and showed significant positive results regarding headache outcomes; however, the best route whether intramuscular, intravenous, or suppository was not compared in the previous studies. Also, both 10 and 20 mg doses of metoclopramide were effective in improving headache outcomes; however, there was no direct comparison between both doses and the 10 mg dose was the most frequently used dosage. In NMA of headache change after 30 min or 1 h, metoclopramide effect came after granisetron, ketorolac, chlorpromazine, and Dexketoprofen trometamol. Only granisetron's effect was significantly higher than metoclopramide's effect which was only significantly higher than placebo and sumatriptan. In headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide which was higher than other medications and showed significantly higher effects only with placebo. In rescue medication, metoclopramide's effect was only non-significantly lower than prochlorperazine and chlorpromazine while its effect was higher than other drugs and showed higher significant effects only than placebo and valproate. In the recurrence rate, studies showed no significant difference between metoclopramide and other drugs. Metoclopramide significantly decreased nausea more than the placebo. Regarding side effects, metoclopramide showed a lower incidence of mild side effects than pethidine and chlorpromazine and showed a higher incidence of mild side effects than placebo, dexamethasone, and ketorolac. The reported extrapyramidal symptoms with metoclopramide were dystonia or akathisia.

A dose of 10 mg IV Metoclopramide was effective in relieving migraine attacks with minimal side effects. Compared to other active drugs, it only showed a lower significant effect compared with granisetron regarding headache change while it showed significantly higher effects only with placebo in both rescue medication needs and headache-free symptoms and valproate in only rescue medication need. Also, it significantly decreased headache scores more than placebo and sumatriptan. However, more studies are needed to support our results.

While systematic reviews have examined medication effectiveness for post-traumatic headache (PTH), they have not assessed tolerability.

To conduct a scoping review to characterize the adverse effects of pharmacotherapy for PTH.

CINAHL, CMA Infobase, Cochrane Library, Embase, Epistemonikos, MEDLINE, PEDro, PsycInfo, Scopus, SportDiscus, TRIP and the University of York Center for Reviews and Dissemination were searched. Studies meeting these criteria were included 1) English language, 2) involved humans with traumatic brain injury (TBI), 3) a medication for PTH was administered and 4) reported tolerability outcomes. Author(s), publication year, country of origin, study design, sample demographics, medication type, comparator, dose, treatment duration, adverse effect type and rate, discontinuation rate, and effectiveness outcomes were extracted.

The search yielded 2941 records; 11 studies were included (n = 324 subjects). All subjects had mild TBI except for one with moderate TBI. The following therapies were examined 1) abortive (dihydroergotamine N = 1; metoclopramide N = 1; indomethacin N = 3), 2) prophylactic (divalproex sodium N = 1; amantadine N = 1; erenumab N = 2; amitriptyline N = 2). No serious adverse effects occurred. Observed adverse effects overlap with common symptoms of TBI.

The unique needs of people with TBI must be considered when instituting pharmacotherapy. More studies specifically evaluating medication tolerability in PTH are needed.

Migraine is one of the most common causes of disability worldwide and the sixth cause of loss of life years due to disability. Migraine is reported mainly in young and middle-aged people, so it can cause a person to face many problems in doing daily tasks. The emergency department annually accepts 1.2 million patients with migraine. Therefore, timely diagnosis of the disease, knowledge of valuable drugs in an emergency, knowing how to use them, and finally, early treatment can play an essential and decisive role in improving patients' symptoms and reducing the disability caused by the disease. An essential and valuable drug category in the emergency department to manage pain is non-opioid intravenous (IV) drugs. Therefore, this study aimed to evaluate non-opioid IV drugs to manage pain in patients with acute migraines in the emergency department.

This study conducted a comprehensive literature review to access the latest scientific studies and documents using keywords (acute migraine, non-opioid IV drugs, pain management) in reliable databases such as PubMed, Scopus, Web of Science, Cochrane, and Google Scholar. We reviewed 87 articles, 53 of which were evaluated and compared.

A review study considers intravenous acetaminophen as a suitable option for the first-line treatment of acute migraine in the emergency department if the patient does not tolerate aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). Various studies have obtained positive effects of NSAIDs and dihydroergotamine (DHE) in treating acute migraine. Prescribing anti-dopaminergic drugs can effectively reduce associated symptoms such as nausea and vomiting. Dexamethasone and magnesium sulfate are effective in preventing migraine and severe attacks. Intravenous sodium valproate is effective in moderate to severe migraine attacks or treatment-resistant migraines. In the emergency department, prescribing intravenous haloperidol, lidocaine, and propofol can help manage migraine and improve other associated symptoms, such as nausea or vomiting.

Non-opioid IV drugs are essential to manage pain and improve other migraine symptoms in the emergency setting. Knowing the above drugs and their optimal use has a decisive role in managing patients with acute migraine in the emergency department.

Metoclopramide may be used to treat people suffering from acute migraine. However, no comprehensive investigation on this issue has been recorded. This review will provide more solid evidence for the use of metoclopramide in treating acute migraine.

To compare the efficacy of intravenous metoclopramide with other therapies in migraine attack treatment in an emergency department (ED).

We included randomized controlled trials of participants older than 18 years with acute migraine headaches, which included at least one arm that received intravenous (IV) metoclopramide at the ED. A literature search of PubMed, Web of Science, Cochrane Collaboration, and Reference Citation Analysis on December 31, 2021 retrieved other drugs or placebo-controlled studies without language limitation. The risk of bias was assessed using the Cochrane risk of bias tool. The primary endpoint was pain reduction at 60 min or closest to 1 h after treatment, as measured by the pain scale. Secondary endpoints included adverse effects or reactions resulting from metoclopramide or comparisons.

Fourteen trials with a total of 1661 individuals were eligible for review. The risk of bias ranged from low to intermediate. IV metoclopramide administration was not associated with higher pain reduction at 1 h (Standard mean difference [SMD] = -0.03, 95% confidence interval [CI]: -0.33-0.28, P = 0.87). However, metoclopramide was associated with better pain reduction than placebo (SMD = 1.04, 95%CI: 0.50-1.58, P = 0.0002). In addition, side effects were not significantly different between IV metoclopramide and other drugs or placebo (odds ratio [OR] = 0.76, 95%CI: 0.48-1.19, P = 0.09 and OR = 0.92, 95%CI: 0.31-2.74, P = 0.54, respectively).

Metoclopramide is more effective than placebo in treating migraine in the ED. Despite the observed tendency of decreased side effects, its effectiveness compared to other regimens is poorly understood. More research on this area is needed to treat migraine in acute care settings effectively.

Headache is one of the most common neurological conditions among emergency department visits (ED), although the best therapy has not been identified yet. Therefore, in the current study, we aimed to compare the pain-relieving effect of metoclopramide and ketorolac in acute primary headaches patients.

This double-blind, randomised clinical trial was conducted at Golestan Hospital, Ahvaz, Iran. This research involved all adult patients with acute primary (migraine or tension-type) headaches presented to the ED. Pain intensity was assessed with 0 to 10 verbal Numeric Rating Scales (NRS). The subjects were randomised into 10 mg intravenous (IV) metoclopramide or 30 mg IV ketorolac groups. Pain score and drug adverse reactions were compared between the two groups at baseline, 15, 30, and 60 min after baseline.

108 patients completed this trial and were equally divided into two groups (mean age of 34 ± 8.54 years; 57.4% female). Before treatment, the mean pain score was 6.9 and 6.8 in metoclopramide and ketorolac groups, respectively (p > 0.05). Metoclopramide failed to provide more improvement in pain score at 30 min (p = 0.55) and 60 min (p = 0.15) from baseline. There were no serious adverse events in this study. Only five patients required rescue medication which four of them were in ketorolac group.

We were unable to reject the null hypothesis that there would be no difference in pain outcomes between metoclopramide and ketorolac.

Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.

To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.

Multiple databases from database inception to February 24, 2021.

Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.

Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small.

The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.

Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.

There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.

To compare the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department (ED).

Migraine is a common, incapacitating neurological condition. Although chlorpromazine and prochlorperazine are known to be safe, efficacious treatments for migraine, they have never been directly compared.

We performed a prospective, randomized, double-blind clinical trial at a tertiary hospital in Melbourne, Australia. Adults aged 18-65 years, who presented with migraine, were eligible for recruitment. Sixty-six patients were randomized to either chlorpromazine 12.5 mg or prochlorperazine 12.5 mg, both infused in 500 ml of sodium chloride 0.9% over 30 min. Headache severity score, nausea severity score, and the presence of photophobia and phonophobia were assessed at 0, 30, 60, and 120 min. Adverse effects and the need for rescue therapy were recorded. The primary outcome was a reduction in headache severity score from baseline at 60 min post-commencement of the study medicine infusion.

Sixty-five patients were included in the analysis. There was a median reduction in headache severity score at 60 min of 3.0 (interquartile range 1.0-4.0) in the chlorpromazine arm versus 2.0 (1.0-4.0) in the prochlorperazine arm (median difference -0.5 (95% confidence interval, -1.9 to 0.9)). We saw no evidence of a difference in secondary outcomes at 30, 60, or 120 min. Side effects were reported in 16/32 (50%) patients in the chlorpromazine group versus 7/33 (21%) in the prochlorperazine group (p = 0.020). Rescue therapy was required in 7/32 (22%) patients in the chlorpromazine group versus 12/33 (36%) in the prochlorperazine group (p = 0.277).

Both chlorpromazine and prochlorperazine are efficacious treatments for acute migraine in adult patients presenting to the ED. This trial found no evidence of superiority of either agent over the other. Caution should be used when prescribing these medicines in the borderline hypotensive patient; in that circumstance, prochlorperazine should be preferentially used.

Migraine is a frequently disabling neurologic condition which can be complicated by medication overuse headache and comorbid medical disorders, including obesity, anxiety and depression. Although most migraine management takes place in outpatient clinics, inpatient treatment is indicated for migraine refractory to multiple outpatient treatments, with intractable nausea or vomiting, need for detoxification from medication overuse (such as opioids and barbiturates), and significant medical and psychiatric disease. The goals of inpatient treatment include breaking the current cycle of headache pain, reducing the frequency and/or severity of future attacks, monitored detoxification of overused medications, and reducing disability and improving quality of life.

Headache is a significant reason for access to Emergency Departments (ED) worldwide. Though primary forms represent the vast majority, the life-threatening potential of secondary forms, such as subarachnoid hemorrage or meningitis, makes it imperative for the ED physician to rule out secondary headaches as first step, based on clinical history, careful physical (especially neurological) examination and, if appropriate, hematochemical analyses, neuroimaging or lumbar puncture. Once secondary forms are excluded, distinction among primary forms should be performed, based on the international headache classification criteria. Most frequent primary forms motivating ED observation are acute migraine attacks, particularly status migrainous, and cluster headache. Though universally accepted guidelines do not exist for headache management in an emergency setting, pharmacological parenteral treatment remains the principal approach worldwide, with NSAIDs, neuroleptic antinauseants, triptans and corticosteroids, tailored to the specific headache type. Opioids should be avoided, for their scarce effectiveness in the acute phase, while IV hydration should be limited in cases of ascertained dehydration. Referral of the patient to a Headache Center should subsequently be an integral part of the ED approach to the headache patients, being ascertained that lack of this referral involves a high rate of relapse and new accesses to the ED. More controlled studies are needed to establish specific protocols of management for the headache patient in the ED.

Metoclopramide is widely used as an abortive migraine therapy due to the advantage of having not only antiemetic, but also analgesic properties. Despite the proven clinical efficacy of metoclopramide in acute migraine, the mechanism of its anti-cephalalgic action has not been entirely elucidated. Taking into account the key role of the trigeminovascular system activation in migraine pathophysiology, we aimed to investigate metoclopramide effects on the excitability of central trigeminovascular neurons and neurogenic dural vasodilation using valid electrophysiological and neurovascular models of trigeminovascular nociception. Extracellular recordings of the activity of second-order dura-sensitive neurons were made in the trigeminocervical complex (TCC) of 16 anaesthetised rats. Cumulative metoclopramide infusion (three steps in 30 min intervals, 5 mg/kg i.v. per step, n = 8) significantly and dose-dependently suppressed both ongoing firing of the TCC neurons and their responses to dural electrical stimulation, maximally to 30%[0-49%] (median[Q1-Q3]) and 4%[0-30%] of the initial level, respectively (both p = 0.001, compared to saline (n = 8)). By contrast, the neurogenic dural vasodilation studied in a separate group of 12 rats was not significantly affected by cumulative infusion of metoclopramide (5 mg/kg i.v. per step, n = 6) compared to both baseline values and the vehicle group (n = 6) (all p > 0.05). These results provide evidence that metoclopramide is unable to affect the peripheral response to trigeminovascular activation, but it does suppress the central response, which is highly predictive of anti-migraine action. Thus, here we show the neurophysiological mechanism underlying the therapeutic efficacy of metoclopramide in migraine.

In this study, we will assess the efficacy and safety of metoclopramide for the treatment of acute migraine (AM).

We will comprehensively search Cochrane Library, PUMBED, EMBASE, Google Scholar, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the inception to July 1, 2019 to identify any eligible studies. Only randomized controlled trials will be considered for inclusion. The study selection, data collection, and management will be completed by two authors independently. The risk of bias will be assessed using Cochrane risk of bias tool. RevMan 5.3 software will be used for statistical analysis.

The primary outcome includes pain intensity, as measured by visual analogue scale or others. The secondary outcomes are success rate, requirement of rescue medicine, quality of life, relapse, and adverse events.

This study will summarize the latest evidence for the clinical efficacy and safety of metoclopramide for the treatment of AM.

PROSPERO CRD42019142795.

Dexamethasone, metoclopramide, ketorolac, and chlorpromazine have been used for the treatment of migraine headache. However, the effectiveness of these drugs in pain relief and prevention of recurrence and their side effects have not been compared yet. This was a randomized, double-blind clinical trial. Subjects were randomized to four groups; each received one of the following drugs intravenously: dexamethasone 8 mg, ketorolac 30 mg, metoclopramide 10 mg, and chlorpromazine 25 mg. The severity of headache in the two groups was assessed at starting point, 1 h and 24 h after the administration of drug using the visual analogue scale (VAS) on a scale of 0 to 10. No significant difference was found in the severity of symptoms between the four study groups before treatment, 1 h, and 24 h after treatment. The effect of all mentioned drugs on acute migraine headache was statistically significant at 1 and 24 h post-treatment compared to baseline. No significant difference was detected in the number of unresponsive cases between the four groups. There was a trend toward higher effectiveness of dexamethasone in prevention of recurrence (P = 0.05). Side effects were more common in chlorpromazine and less common in the dexamethasone-treated patients (P < 0.001). The present clinical trial shows the effectiveness of dexamethasone in prevention of recurrence and low frequency of treatment side effects.

The claim that parenteral dihydroergotamine (DHE) is effective in migraine is based on one randomized, placebo-controlled, crossover trial from 1986. The aim of this review was to critically evaluate the original article. It was also found to be of interest to review quotes concerning the results in the more than 100 articles subsequently referring to the article.

The correctness of the stated effect of intravenous DHE in the randomized clinical trial (RCT) was first critically evaluated. Then, Google Scholar was searched for references to the article and these references were classified as to whether they judged the reported RCT as positive or negative.

The design of the RCT, with a crossover within one migraine attack, only allows evaluation of the results for the first period and the effect of DHE and placebo were quite comparable. About 151 references were found for the article in Google scholar. Among the 95 articles with a judgment on the efficacy of intravenous DHE in the RCT, 90 stated that DHE was effective or likely effective whereas only 5 articles stated that DHE was ineffective.

Despite a "negative" RCT, authors of subsequent articles on the efficacy of parenteral DHE overwhelmingly reported this RCT as "positive." This is probably due to the fact that the authors concluded in the abstract that DHE is effective, and to a kind of "wrong general consensus."

To provide evidence-based treatment recommendations for adults with acute migraine who require treatment with injectable medication in an emergency department (ED). We addressed two clinically relevant questions: (1) Which injectable medications should be considered first-line treatment for adults who present to an ED with acute migraine? (2) Do parenteral corticosteroids prevent recurrence of migraine in adults discharged from an ED?

The American Headache Society convened an expert panel of authors who defined a search strategy and then performed a search of Medline, Embase, the Cochrane database and clinical trial registries from inception through 2015. Identified articles were rated using the American Academy of Neurology's risk of bias tool. For each medication, the expert panel determined likelihood of efficacy. Recommendations were created accounting for efficacy, adverse events, availability of alternate therapies, and principles of medication action.

The search identified 68 unique randomized controlled trials utilizing 28 injectable medications. Of these, 19 were rated class 1 (low risk of bias), 21 were rated class 2 (higher risk of bias), and 28 were rated class 3 (highest risk of bias). Metoclopramide, prochlorperazine, and sumatriptan each had multiple class 1 studies supporting acute efficacy, as did dexamethasone for prevention of headache recurrence. All other medications had lower levels of evidence.

Intravenous metoclopramide and prochlorperazine, and subcutaneous sumatriptan should be offered to eligible adults who present to an ED with acute migraine (Should offer-Level B). Dexamethasone should be offered to these patients to prevent recurrence of headache (Should offer-Level B). Because of lack of evidence demonstrating efficacy and concern about sub-acute or long-term sequelae, injectable morphine and hydromorphone are best avoided as first-line therapy (May avoid-Level C).

Migraine is one of the most common causes of headache presentations to emergency departments (EDs). Patients with migraine attack need rapid pain relief rather than diagnostic modalities. Metoclopramide, a dopamine antagonist with a primary use of antiemetic, has been used commonly in ceasing migraine attack. An earlier meta-analysis favors metoclopramide over placebo but includes studies with significant methodological errors and heterogeneity. The present article aimed to review the literature to reveal studies comparing metoclopramide to either placebo or active comparators. A literature search including PubMed, Cochrane Database, and Google Scholar was performed by using the evidence-based process for determining the study quality. Although the studies comparing parenteral metoclopramide to placebo in ceasing migraine headache favor metoclopramide to placebo and lower rates of rescue drug need, however, they lack high methodological quality even to perform a meta-analysis. Meanwhile, the effect of metoclopramide in ceasing migraine headache is also comparable to active comparators. It seems reasonable to use metoclopramide in migraine attacks in EDs according to the current literature. However, further studies with high methodological quality are needed to reveal whether and how much metoclopramide is superior to placebo.

There is a considerable amount of practice variation in managing migraines in emergency settings, and evidence-based therapies are often not used first line.

A peer-reviewed search of databases (MEDLINE, Embase, CENTRAL) was carried out to identify randomized and quasi-randomized controlled trials of interventions for acute pain relief in adults presenting with migraine to emergency settings. Where possible, data were pooled into meta-analyses.

Two independent reviewers screened 831 titles and abstracts for eligibility. Three independent reviewers subsequently evaluated 120 full text articles for inclusion, of which 44 were included. Individual studies were then assigned a US Preventive Services Task Force quality rating. The GRADE scheme was used to assign a level of evidence and recommendation strength for each intervention.

We strongly recommend the use of prochlorperazine based on a high level of evidence, lysine acetylsalicylic acid, metoclopramide and sumatriptan, based on a moderate level of evidence, and ketorolac, based on a low level of evidence. We weakly recommend the use of chlorpromazine based on a moderate level of evidence, and ergotamine, dihydroergotamine, lidocaine intranasal and meperidine, based on a low level of evidence. We found evidence to recommend strongly against the use of dexamethasone, based on a moderate level of evidence, and granisetron, haloperidol and trimethobenzamide based on a low level of evidence. Based on moderate-quality evidence, we recommend weakly against the use of acetaminophen and magnesium sulfate. Based on low-quality evidence, we recommend weakly against the use of diclofenac, droperidol, lidocaine intravenous, lysine clonixinate, morphine, propofol, sodium valproate and tramadol.

We compare metoclopramide 20 mg intravenously, combined with diphenhydramine 25 mg intravenously, with ketorolac 30 mg intravenously in adults with tension-type headache and all nonmigraine, noncluster recurrent headaches.

In this emergency department (ED)-based randomized, double-blind study, we enrolled adults with nonmigraine, noncluster recurrent headaches. Patients with tension-type headache were a subgroup of special interest. Our primary outcome was a comparison of the improvement in pain score between baseline and 1 hour later, assessed on a 0 to 10 verbal scale. We defined a between-group difference of 2.0 as the minimum clinically significant difference. Secondary endpoints included need for rescue medication in the ED, achieving headache freedom in the ED and sustaining it for 24 hours, and patient's desire to receive the same medication again.

We included 120 patients in the analysis. The metoclopramide/diphenhydramine arm improved by a median of 5 (interquartile range 3, 7) scale units, whereas the ketorolac arm improved by a median of 3 (IQR 2, 6) (95% confidence interval [CI] for difference 0 to 3). Metoclopramide+diphenhydramine was superior to ketorolac for all 3 secondary outcomes: the number needed to treat for not requiring ED rescue medication was 3 (95% CI 2 to 6); for sustained headache freedom, 6 (95% CI 3 to 20); and for wish to receive the same medication again, 7 (95% CI 4 to 65). Tension-type headache subgroup results were similar.

For adults who presented to an ED with tension-type headache or with nonmigraine, noncluster recurrent headache, intravenous metoclopramide+diphenhydramine provided more headache relief than intravenous ketorolac.

Migraine is a common reason for visits to the emergency room. Attacks that lead patients to come to the emergency room are often more severe, refractory to home rescue medication, and have been going on for longer. All of these features make these attacks more challenging to treat. The purpose of this article is to review available evidence pertinent to the treatment of acute migraine in adults in the emergency department setting in order to provide neurologists with a rational approach to management. Drug classes and agents reviewed include opioids, dopamine receptor antagonists, triptans, nonsteroidal anti-inflammatory drugs, corticosteroids, and sodium valproate.

The impact of treatment given upon discharge on the "bounce back" rate was ascertained in children presenting at the emergency department for treatment of status migrainosus. All children ages 8 to 17 years old presenting to an emergency department in 2008 who were treated for status migrainosus and discharged home were included. Of the total of 187 patients, 21 patients (11.2%) bounced back. Treatment given was not associated with the bounce back rate. The only factors reaching significance were the presence of a migraine equivalent in 28.6% of patients who bounced back as compared with only 6.7% in patients without recurrence (P = .006); brain imaging study in the emergency department (52.4% vs. 16.9%, P = .001); and an arranged physician follow-up (66.6% vs. 36.3%, P = .01). The results appear to suggest that no current treatment given to children presenting to the emergency department with status migrainosus seems to alter the immediate recurrence rate.

Adults seeking treatment at hospitals' Emergency Departments (EDs) because of headache represent a major health-care issue. To date, there are no special guidelines for management of primary headache in adults seen at EDs and therapeutic approaches are often inconsistent. This review describes the therapeutic strategies that are most frequently used to treat primary headache in adult ED patients and their in situ efficacy, based on literature data, the type of medications studied in randomized clinical trials for the management of adult ED patients, and the recommendations found in the guidelines for symptomatic treatment of migraine. We also report on the experience of the Parma University Hospital ED in the year 2007 for the management of adult patients diagnosed with primary headache. Finally, we propose an algorithm for primary headache management in ED patients, which is based on the literature data and clinical experience, and is suitable for application in Italy.

Multiple parenteral medications are used to treat migraine and other acute primary headaches in the emergency department (ED). Regardless of specific headache diagnosis, no medication eliminates the frequent recurrence of primary headache after ED discharge. It is uncertain which medication primary headache patients should be given on discharge from an ED. The aim of this study is to compare the efficacy of oral sumatriptan with naproxen for treatment of post-ED recurrent primary headache.

This was a randomized, double-blind efficacy trial. We randomized patients to either naproxen 500 mg or sumatriptan 100 mg for headache recurrence after ED discharge. Patients were eligible if they received parenteral therapy for an acute exacerbation of a primary headache in the ED. Patients who met established criteria for migraine without aura were designated a priori as a homogenous subgroup of interest. We followed all patients by telephone 48 hours after ED discharge. The primary endpoint was the between-group difference in change in pain intensity during the 2-hour period after ingestion of either 500 mg naproxen or 100 mg sumatriptan. This difference was measured on a validated 11-point (0 to 10) verbal numeric rating scale (NRS). Satisfaction with the medication and adverse effects were also assessed. Patients who met criteria for migraine without aura were analyzed twice according to a priori design: once as a homogenous subgroup and then again combined with all other primary headaches.

Of 410 patients randomized, 383 (93%) had outcome data available for analysis. Two hundred eighty (73%; 95% confidence interval [CI] 68% to 77%) reported headache post-ED discharge and 196 (51%; 95% CI 44% to 58%), including 88 with migraine, took the investigational medication provided to them. The naproxen group improved by a mean of 4.3 NRS points, whereas the sumatriptan group improved by 4.1 points (95% CI for difference of 0.2 points: -0.7 to 1.1 points). Findings were virtually identical among the migraine subset (4.3 versus 4.2 NRS points; 95% CI for difference of 0.1 points: -1.3 to 1.5 points). Seventy-one percent (95% CI 62% to 80%) of naproxen patients and 75% (95% CI 66% to 84%) of sumatriptan patients would want to take the same medication the next time. Adverse effect profiles were also comparable.

In this trial, nearly three quarters of patients reported headache recurrence within 48 hours of ED discharge. Naproxen 500 mg and sumatriptan 100 mg taken orally relieve post-ED recurrent primary headache and migraine comparably. Clinicians should be guided by medication costs, contraindications, and a patient's previous experience with the medication.

Although many high-quality migraine clinical trials have been performed in the emergency department (ED) setting, almost as many different primary outcome measures have been used, making data aggregation and meta-analysis difficult. The authors assessed commonly used migraine trial outcomes in two ways. First, the authors examined the association of each commonly used outcome versus the following patient-centered variable: the research subject's wish, when asked 24 hours after investigational medication administration, to receive the same medication the next time they presented to an ED with migraine ("would take again"). This variable was chosen as the criterion standard because it provides a simple, dichotomous, clinically sensible outcome, which allows migraineurs to factor important intangibles of efficacy and adverse effects of treatment into an overall assessment of care. The second part of the analysis assessed how sensitive to true efficacy each outcome measure was by calculating sample size requirements based on results observed in previously conducted clinical trials.

This was a secondary analysis of data previously collected in four ED-based migraine randomized trials performed between 2003 and 2007. In each of these trials, subjects were asked 24 hours after administration of an investigational medication whether or not they would want to receive the same medication the next time they came to the ED with a migraine. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for sex and medication received, were calculated as measures of association between the most commonly used outcome measures and "would take again." The sensitivity of each outcome measure to treatment efficacy was determined by calculating the sample size that would be required to detect a statistically significant result using estimates of that outcome obtained in two clinical trials.

Data from 378 subjects were used for this analysis. Adjusted ORs for association of "would take again" and other commonly used primary headache outcomes are as follows: achieving a pain-free state by 2 hours, OR = 3.1 (95% CI = 1.8 to 5.4); sustained pain-free status, OR = 4.5 (95% CI = 1.9 to 11.0); and no need for rescue medication, OR = 3.7 (95% CI = 2.1 to 6.6). An improvement on a standardized 11-point pain scale of > or =33% had an adjusted OR = 5.2 (95% CI = 2.2 to 12.4). The best performing alternate outcome, > or =33% improvement, correctly classified 288 subjects and misclassified 77 subjects when compared to "would take again." At least 33% improvement and pain-free by 2 hours required the smallest sample sizes, while sustained pain-free and "would take again" required many more subjects.

"Would take again" was associated with all migraine outcome measures we examined. No individual outcome was more closely associated with "would take again" than any other. Even the best-performing alternate outcome misclassified more than 20% of subjects. However, sample sizes based on "would take again" tended to be larger than other outcome measures. On the basis of these findings and this outcome measure's inherent patient-centered focus, "would take again," included as a secondary outcome in all ED migraine trials, is proposed.

We investigated the difference in incidence of acute akathisia related to the rate of infusion in patients receiving metoclopramide for acute nausea, vomiting, or migraine headache in the emergency department (ED).

Randomized, prospective, double-blind clinical trial of patients aged 18 years and older who were to receive intravenous metoclopramide for the treatment of nausea, vomiting, or headache were eligible. Patients were excluded if they were taking medications that might mimic or mask akathisia, had a movement disorder, renal insufficiency, or were unable or unwilling to consent. Pregnant women and prisoners were also excluded. Subjects were randomized to receive 1 of 2 accepted metoclopramide administration regimens. The regimens included 10 mg of metoclopramide administered either as a 2-minute bolus (BG) or as a slow infusion for 15 minutes (IG). All patients received a normal saline placebo at the opposite rate to maintain blinding. The main outcome was development of akathisia noted at 60 minutes after drug administration as measured either with The Prince Henry Hospital akathisia rating scale or by sudden unexplained departure from the ED during treatment.

One hundred twenty-seven patients were eligible for the study. Fifty-nine patients met exclusion criteria. Of the remaining 68 patients, 36 were randomized to the BG and 32 were randomized to the IG. In the BG, 11.1% of patients developed akathisia compared with 0% in the IG (P = .026). Four patients developed akathisia based on the scale and 2 departed suddenly from the ED.

Slower infusion of metoclopramide reduces the incidence of akathisia.

Prokinetic agents are effective not only for disease of the gastrointestinal (GI) tract but also for those external to the GI tract such as the central nervous system, and the respiratory, urologic, and metabolic organs. This article reviews the effectiveness of prokinetic agents against diseases external to the GI tract. Studies were identified by computerized and manual searches of the available literature. A Medline search was performed (1975-July, 2008) using the following medical subject headings: prokinetic agent, metoclopramide, domperidone, trimebutine, cisapride, itopride, mosapride, tegaserod, and human. The identified diseases for which prokinetic agents may be effective are various: bronchial asthma, chronic cough, hiccup, spontaneous bacterial peritonitis, cholelithiasis, diabetes mellitus, acute migraine, Parkinson's disease, anorexia nervosa, Tourette's disorder, urologic sequelae of spinal cord injury and of radical hysterectomy for cervical cancer, laryngeal dysfunction and so on. These agents are also useful for prevention of aspiration pneumonia during anesthesia, and in tube-fed patients. Prokinetic agents should be a valuable addition to our currently limited pharmacological armamentarium not only for functional bowel disease, but also for diseases external to the GI tract.

Although not recommended for low back pain, the efficacy of systemic corticosteroids has never been evaluated in a general low back pain population. To test the efficacy of systemic corticosteroids for Emergency Department (ED) patients with low back pain, a randomized, double-blind, placebo-controlled trial of long-acting methylprednisolone was conducted with follow-up assessment 1 month after ED discharge. Patients with non-traumatic low back pain were included if their straight leg raise test was negative. The primary outcome was a comparison of the change in a numerical rating scale (NRS) 1 month after discharge. Of 87 subjects randomized, 86 were successfully followed to the 1-month endpoint. The change in NRS between discharge and 1 month differed between the two groups by 0.6 (95% confidence interval -1.0 to 2.2), a clinically and statistically insignificant difference. Disability, medication use, and healthcare resources utilized were comparable in both groups. Corticosteroids do not seem to benefit patients with acute non-radicular low back pain.

Although various classes of medication are used to treat acute migraine in the emergency department (ED), no treatment offers complete pain relief without side effects or recurrence of headache. Consequently, even though several antiemetic medications as well as SQ sumatriptan have demonstrated efficacy and tolerability for the ED treatment of migraine, there remains a need for more effective parenteral therapies. Open-label studies suggest that the combination of trimethobenzamide and diphenhydramine (TMB/DPH) may provide effective relief in a high proportion of migraineurs.

To test the hypothesis that ED patients with acute migraine, given intramuscular TMB/DPH, would have a larger reduction in their pain scores than patients given SQ sumatriptan.

This was an ED-based, randomized, double-blind, "double-dummy" clinical trial comparing 2 parenteral treatments for acute migraine headaches. Subjects received a combination of TMB 200 mg and DPH 25 mg as a single intramuscular injection or 6 mg of SQ sumatriptan. Pain scores, disability scores, associated symptoms, and adverse effects were assessed for 2 hours in the ED and by telephone 24 hours after medication administration. The primary outcome was the between-group difference in reduction of pain intensity as measured by a validated numerical rating scale 2 hours after medication administration. This study was designed to detect superiority of TMB/DPH; therefore, a 1-tailed t-test was used. An interim analysis was planned to terminate the trial if predetermined endpoints in the primary outcome variable were reached.

The trial was stopped by the data monitoring committee after 40 subjects were enrolled because a substantial benefit in the primary outcome was found favoring sumatriptan. Baseline pain scores were comparable between the 2 groups. By 2 hours, sumatriptan subjects had improved by a mean of 6.1 and the TMB/DPH subjects had improved by a mean of 4.4 (95% CI for difference of 1.7: -0.1 to 3.4). By 24 hours after medication administration, sumatriptan subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB (95% CI for difference of -0.4: -2.4 to 1.6). The need for rescue medication was comparable between the groups. No serious or frequent adverse effects were noted in either group.

SQ sumatriptan is probably superior to TMB/DPH for treating the pain of acute migraine at 2 hours. However, TMB/DPH was well-tolerated, efficacious, and relieved pain comparably to sumatriptan at 24 hours. TMB/DPH might have a role in select populations in which sumatriptan is contraindicated or likely to be ineffective.

Migraine is common during pregnancy, but fortunately this combination of conditions obviously exists for only a finite period. The greatest frequency of migraine attacks occurs during the first trimester. Accurate diagnosis is a sine qua non in this setting as in any headache patient. It is in the first trimester that the fetus is at greatest risk from abortifacient and teratogenic drugs, and when very early pregnancy may be undiagnosed. Ergot alkaloids (including methysergide) should be avoided during pregnancy because of their teratogenicity, and most other drug classes should be used only when unavoidable. The use of prophylactic agents during pregnancy should be the exception, not the rule, and preferably only during the second and third trimesters; propranolol is probably safest in this situation. De novo headache during pregnancy usually requires expert review of the patient. Treatment tactics for uncomplicated migraine in pregnancy depend on the concurrent clinical situation. Paracetamol (acetaminophen) is the mainstay for the patient whose typical attacks continue into the first trimester. If paracetamol is insufficient, then partial agonist opioids may be used if typical migraine attacks persist in the second and third trimesters (which is uncommon). 'Chronic migraine' in pregnancy, i.e. >or=15 headache days per month, is rare, and is the greatest therapeutic challenge. Co-morbidities such as depression or epilepsy require specialised approaches. The complexities associated with these tactics are discussed in this article, and it is emphasised that none has the specific approval of regulatory authorities. Heightened pharmacovigilance will better inform the future pregnant migraineur. However, this type of information is less likely to be available for novel classes of neuropharmacological agents than for existing ones.

Difficult clinical decisions are a part of every emergency practitioner's life. Dealing with difficult patients and recalcitrant consultants is seldom enjoyable, but can be made more palatable through the use of some of the clinical strategies contained in this article. Knowledge of the current best evidence and a willingness to discard outdated practice ideas will help ensure that emergency practitioners continue to provide state-of-the-art medical care. Expressions of care, concern, and respect for patients' problems, and development of a therapeutic alliance with these patients will maximize patient, and ultimately physician, satisfaction.

To review the mechanism of action of neuroleptics, the evidence for their efficacy, and their clinical use in headache treatment.

Neuroleptics and antiemetics have long been used for headache treatment; however, they have not been widely utilized because of general unfamiliarity with them and concerns about their adverse events. With the recent advent of the atypical neuroleptics and their improved adverse event profile, our armamentarium for headache treatment has expanded. In this review, we explore the mechanism of action of these classes of drugs, their adverse events, and the evidence for their efficacy. We also detail our experience with the different drugs and how we use them as both acute and preventive headache therapy.

A review of published literature was obtained through a MEDLINE search on the use of neuroleptics in headache therapy.

Neuroleptics have widespread evidence supporting their use in headache treatment and present an important part of the armaterium against headache.

To assess the evidence from controlled trials on the efficacy and tolerability of parenteral metoclopramide for acute migraine in adults.

Cochrane Central Register of Controlled Trials, Medline, Embase, LILACS, CINAHL, conference proceedings, clinical practice guidelines, and other sources.

Randomised controlled trials of parenteral metoclopramide for acute migraine in adults.

We reviewed 596 potentially relevant abstracts and found 13 eligible trials totalling 655 adults. In studies comparing metoclopramide with placebo, metoclopramide was more likely to provide significant reduction in migraine pain (odds ratio 2.84, 95% confidence interval 1.05 to 7.68). Used as the only agent, metoclopramide showed mixed effectiveness when compared with other single agents. Heterogeneity of studies for combination treatment prevented statistical pooling. Treatments that did include metoclopramide were as, or more, effective than comparison treatments for pain, nausea, and relapse outcomes reported in all studies.

Metoclopramide is an effective treatment for migraine headache and may be effective when combined with other treatments. Given its non-narcotic and antiemetic properties, metoclopramide should be considered a primary agent in the treatment of acute migraines in emergency departments.

We studied the efficacy of dexamethasone (4 mg) and haloperidol (5 mg) in the treatment of migraine in the emergency room. Twenty nine patients who had diagnosis of migraine according to the International Headache Society criteria and were evaluated for a painful episode at the emergency room of Santa Casa of São Paulo were included. All the patients scored their pain in 10 when evaluated, even after the use of intravenous analgesia (dipyrone). Fourteen patients were treated with haloperidol and the remaining 15 received dexamethasone. The patients were asked about pain intensity at 30, 60, 90 and 120 minutes after the use of either the drugs. Both drugs were equally efficient in pain relief after two hours. Patients who were treated with haloperidol showed an important improvement (more than 50% of improve in the analogic pain scale) in the first 30 minutes. The dexamethasone treated patients only reached this grade of analgesia after 120 minutes. Although we studied a small series of patients, our data suggest that both drugs are efficient in the treatment of a refractory migraine attack. Haloperidol seemed to work quickly in pain relief. No important side effects were observed in neither groups.

To compare analgesic effects of metoclopramide (MTP), pethidine (PET), and combination of metoclopramide-pethidine (M-PET) in the treatment of adult patients with acute primary vascular and tension type headache admitted in the emergency department (ED).

All consecutive adult patients admitted into a university hospital ED in six months with acute vascular and tension type headache were recruited. The patients whose complaints had lasted no longer than seven days were randomised to four groups and thereby received 10 mg MTP intravenously plus placebo intramuscularly (MTP), 10 mg MTP intravenously plus 50 mg PET intramuscularly (M-PET), 50 mg PET intramuscularly plus placebo intravenously (PET); and intramuscular and intravenous placebo (PLC) in a blinded fashion. The patients were asked to report the degree of pain at 0, 15, 30, and 45 minutes on visual analogue scale (VAS) and demographic data and any side effects encountered were recorded. Rescue medication was used if required by the patient because of poor pain relief.

Data regarding 336 patients meeting inclusion criteria were analysed. Mean VAS values recorded at 45 minutes were significantly higher in PLC group than in others (p = 0.000). When the PLC group was excluded, VAS scores in MTP and M-PET groups were significantly lower than in PET group (p = 0.038). Though unimportant, the incidence of side effects recorded in PET group was found to be significantly higher than in the other groups (p = 0.003).

These data suggest that MTP produces more effective analgesia than PET in both vascular and tension type headache in patients with acute primary headache episodes.

The purpose of the research presented in this article was to characterize restless leg syndrome (RLS) in a headache population and correlate treatment induced risks with dopamine blockers. Fifty patients with severe headache who were admitted to an outpatient infusion center were enrolled. The diagnosis of RLS was established using the International Restless Leg Syndrome Study Group criteria. Patients were screened for baseline akathisia using an akathisia scale and reexamined for akathisia after receiving intravenous infusion with one of four dopamine receptor blocking agents as treatment for their headaches. A change from baseline to post-infusion assessment of two points on a global assessment of akathisia was considered positive for drug-induced akathisia. Our results indicated that 41 (82%) of patients had episodic or chronic migraine. The rest had new daily persistent headache, cluster, or posttraumatic headache. Seventeen subjects (34%) met the criteria for RLS. Nineteen (38%) of the subjects developed drug-induced akathisia. Thirteen (76.5%) of the subjects with RLS developed akathisia compared with only 6 of the 33 (18.2%) without RLS (P<.0001). Finally, we concluded that headache patients with RLS are at a greatly increased risk of developing drug-induced akathisia when treated with intravenous dopamine receptor blocking agents.