Objective.-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?Methods.-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.Results/Conclusions.-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.Recommendations.-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).

Objective.-The final section of this 3-part review analyzes published reports involving the acute treatment of migraine with opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids in the emergency department (ED), urgent care, and headache clinic settings, as well as post-discharge medications. In the Conclusion, there is a general discussion of all the therapies presented in the 3 sections.Method.-Using the terms ("migraine" AND "emergency") AND ("therapy" OR "treatment"), the author searched MEDLINE for reports from ED and urgent care settings that involved all routes of medication delivery. Reports from headache clinic settings were included only if medications were delivered by a parenteral route.Results.-Seventy-five reports were identified that compared the efficacy and safety of multiple acute migraine medications for rescue. Of the medications reviewed in Part 3, opioids, NSAIDs, and steroids all demonstrated some effectiveness. When used alone, nalbuphine and metamizole were superior to placebo. NSAIDs were inferior to the combination of metoclopramide and diphenhydramine. Meperidine was arguably equivalent when compared with ketorolac and dihydroergotamine (DHE) but was inferior to chlorpromazine and equivalent to the other dopamine antagonists. Steroids afford some protection against headache recurrence after the patient leaves the treatment center.Conclusions.-All 3 opioids most frequently studied -meperidine, tramadol, and nalbuphine -were superior to placebo in relieving migraine pain, although meperidine combined with promethazine was not. Opioid side effects included dizziness, sedation, and nausea. With ketorolac being the most frequently studied drug in the class, NSAIDs were generally well tolerated, and they may provide benefit even when given late in the migraine attack. The rate of headache recurrence within 24-72 hours after discharge from the ED can be greater than 50%. Corticosteroids can be useful in reducing headache recurrence after discharge. As discussed in Parts 1, 2, and 3, there are effective medications for provider-administered "rescue" in all the classes discussed. Prochlorperazine and metoclopramide are the most frequently studied of the anti-migraine medications in the emergent setting, and their effectiveness is superior to placebo. Prochlorperazine is superior or equivalent to all other classes of medications in migraine pain relief. Although there are fewer studies involving sumatriptan and DHE, relatively "migrainespecific" medications, they appear to be equivalent to the dopamine antagonists for migraine pain relief. Lack of comparisons with placebo and the frequent use of combinations of medications in treatment arms complicate the comparison of single agents to one another. When used alone, prochlorperazine, promethazine, metoclopramide, nalbuphine, and metamizole were superior to placebo. Droperidol and prochlorperazine were superior or equal in efficacy to all other treatments, although they also are more likely to produce side effects that are diffic...

Objectives.-This second portion of a 3-part series examines the relative effectiveness of headache treatment with neuroleptics, antihistamines, serotonin antagonists, valproate, and other drugs (octreotide, lidocaine, nitrous oxide, propofol, and bupivacaine) in the setting of an emergency department, urgent care center, or headache clinic.Methods.-MEDLINE was searched using the terms "migraine" AND "emergency" AND "therapy" OR "treatment." Reports were from emergency department and urgent care settings and involved all routes of medication delivery. Reports from headache clinics were only included if medications were delivered by a parenteral route.Results.-Prochlorperazine, promethazine, and metoclopramide, when used alone, were superior to placebo. Droperidol and prochlorperazine were superior or equal in efficacy to all other treatments, although they also have more side effects (especially akathisia). Metoclopramide was equivalent to prochlorperazine and, when combined with diphenhydramine, was superior in efficacy to triptans and non-steroidal anti-inflammatory drugs. Meperidine was inferior to chlorpromazine and equivalent to the other neuroleptics. The overall percentage of patients with pain relief after taking droperidol and prochlorperazine was equivalent to sumatriptan.Conclusions.-Prochlorperazine and metoclopramide are the most frequently studied of the anti-migraine medications in the emergent setting, and the effectiveness of each is superior to placebo. Prochlorperazine is superior or equivalent to all other classes of medications in producing migraine pain relief. Dopamine antagonists, in general, appear to be equivalent for migraine pain relief to the migraine-"specific" medications sumatriptan and dihydroergotamine, although there are fewer studies involving the last two. Lack of comparisons to placebo and the frequent use of combination medications in treatment arms complicate the comparison of single agents to one other.Key words: migraine, emergency, treatment, DHE, triptan, magnesium (Headache 2012;52:292-306) NOTE TO THE READERIn part 1 of this review, results of trials involving triptans, dihydroergotamine, and magnesium as rescue medications for migraine administered in emergency departments, urgent care centers, and headache clinic infusion centers were reviewed. Pertinent information concerning migraine pathophysiology and the methodology commonly used for studies of rescue migraine therapy also were included. This article (part 2) focuses on similar studies involving neuroleptics, antihistamines, serotonin antagonists, valproate, and other assorted medications (octreotide, lidocaine, nitrous oxide, propofol, and bupivacaine). Part 3 will address studies involving opioids, non-steroidal anti-inflammatory drugs, steroids, and post-discharge medications.Explanation of Methodology.-When drugs from 2 different classes of medications were compared,

Although there are relatively few studies involving health-care provider-administered triptans or DHE for acute rescue, they appear to be equivalent to the dopamine antagonists for migraine pain relief. The relatively rare inclusion of a placebo arm and the frequent use of combination medications in active treatment arms complicate the comparison of single agents with each other.

The effect of prenatal cocaine on acoustic sensorineural reactivity was assessed using reflex modification procedures in infants born to mothers with cocaine abuse (C-exposed). Reflex modification was tested using a controlled eyeblink-eliciting tap to the glabella presented either alone or with a 90-dB SPL tone. The results from 19 C-exposed infants were compared to 19 healthy matched drug-free infants. ANOVA comparison of the two groups showed C-exposed infants were more reactive in general, as indicated by a larger glabellar reflex, and more responsive to auditory stimuli, as indicated by an increased blink when the tone accompanied the tap (p < 0.05). These data suggest that in utero cocaine exposure may have a direct effect on sensorineural processing and may place these infants at risk for cognitive and/or neurological sequelae.