Table 1 General characteristics of the included studies
ID | Country | Study design | Inclusion criteria | Exclusion Criteria | Migraine attack | Study groups | Time report | Scale of pain | Use of migraine medication | Diagnosis of migraine | Conclusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
Friedman et al. 2020 [37] | US | Double-dummy RCT | • Age ≥18 years • Presentation to the ED with moderate / severe H/A that met International Classification of Headache Disorders, 3rd edition migraine criteria - with or without aura - probable migraine with aura - probable migraine without aura, provided they had ≥1 similar attack previously - Status migrainosus, prolonged duration of H/A (>72 h) - Early presentation (< 4 h) | Having at least one of the following: • Consent could not be obtained • Secondary cause of headache • Contraindications to GONB (skull defect, suspected infection overlying injection site, known bleeding disorder, ongoing use of antiplatelet agents or anticoagulants) • prior treatment with GONB • Contraindication or allergy to the study drugs • Pregnant / lactating | Acute attack | Metoclopramide 10 mg IV drip + sham GONB consisting of 6 ml saline (48 patients) Bupivacaine 0.5% 6 ml + IV drip normal saline (51 patients) | Baseline 1 h | 11-point scale 0 = no pain, 10 = imaginable pain & Descriptive headache intensity scale none, mild, moderate, severe | Metoclopramide group: 36 patients received drugs for headache before ED visit Bupivacaine group: 32 patients received drugs for headache before ED visit | International Classification of Headache Disorders, 3rd edition migraine criteria 2013 | Authors conclude that metoclopramide could improve pain intensity more than GONB as first line for ttt acute migraine attack |
Both drugs injected adjacent to greater occipital nerve bilaterally, Administrated over 15 min | |||||||||||
Yavuz et al. 2020 [31] | Turkey | Superiority trial prospective double blinded RCT | • Age: ≥ 18 • Patients were diagnosed as acute migraine headache by emergency medicine physician according to diagnostic criteria of the International Headache Association • Patients were enrolled in the study consecutively 24 h a day, 7 days a week | • Refused to participate in the study • Pregnancy • Taking any analgesic medication within 6 h before presentation to ED • Having other diseases (e.g., hypertension, hypoglycemia, chronic kidney failure, and intracranial masses) • Hemodynamically unstable • Allergy to study drugs | Acute attack | Metoclopramide 10 mg IV (50 patients) Dexketoprofen trometamol 50 mg IV (50 patients) Metoclopramide 10 mg IV + Dexketoprofen 50 mg (50 patients) | Baseline 15 min 30 min | VAS | -- | International Headache Association 2004 | At 15 min, there was non-significant difference between gps (p = 0.09) At 30 min: the combination could significantly decrease pain more than other gps (p = 0.004) |
Khazaei et al. 2019 [28] | Iran | prospective double blinded RCT | • Headaches which met the IHS criteria for migraine • Episodic migraine and did not take preventive therapies • Patients did not have repeated referrals to ED • Headache intensity was higher than 4 on VAS | Having at least one of: • Hypertension • Renal or hepatic failure • Cardiac or respiratory disease • Malignancy • Acute inflammatory disease or infection • Peptic ulcer • Pregnancy / lactation • Neurological deficit • History of immunesuppressive drugs • Epilepsy • Ergotamine use in the past 8 h • Anxiolytic use in the previous 4 h • Life threatening causes of H/A: SAH, meningitis, arterial dissection, or high intracranial pressure | Acute attack | Metoclopramide 10 mg IV (32 patients) Dexamethasone 8 mg IV (32 patients) Chlorpromazine 25 mg IV (32 patients) Ketorolac 30 mg IV (32 patients) | Baseline 1 h 24 h | VAS | All patients didn’t take preventive therapies | International Headache Society (HIS) 2004 | Authors conclude that all drugs could significantly decrease pain of acute migraine attack (p < 0.05); however, there was non-significant difference between the four drugs (p = 0.07) |
Doğan et al. 2019 [35] | Turkey | Prospective double blinded RCT | • Age: >18 years old • Presentation to the ED with migraine‐type headaches and met International Headache Society (IHS) migraine criteria | • Taking analgesic drugs during the previous 2 h • Pregnant • Had documented or declared allergies to metoclopramide • Hemodynamically unstable • Refuse to participate in this research | Acute attack | Metoclopramide 10 mg (74 patients) Normal saline 100 ml (74 patients) | Baseline 15 min 30 min | NRS | metoclopramide group: 69 pts had history of migraine, 18 pts use migraine drugs Placebo group: 65 pts had history of migraine, 24 pts use migraine drugs | International Headache Society (IHS) migraine criteria 3rd edition beta version | Authors conclude that there was no difference between metoclopramide and saline for ttt acute attack of migraine |
Both drugs infused over 10 min | |||||||||||
Amiri et al. 2017 [32] | Iran | Prospective double blinded RCT | • Age: >18 years old • Presenting with headache with a previous history of migraine headache diagnosed by a neurologist | • Pregnant / lactating • Suddenly initiated headache (different from the previous attacks) • Abnormal neurologic findings or head trauma within the last month • Uncooperative • Needed for additional doses of morphine • Had an uncertain diagnosis | Acute attack | Metoclopramide 10 mg IV bolus (73 patients) Granisetrone 2 mg IV bolus (75 patients) | Baseline 1 h 2 h 4 h | VAS | -- | Diagnosis by neurologist | Authors conclude that grabisetrone could significantly decrease pain more than metoclopramide (p = 0.03) |
Friedman et al. 2014 [38] | US | Double blinded RCT | • Acute migraine or acute probable migraine headache as defined by the International Headache Society’s International Classification of Headache Disorders, second edition 2004 • Patients with acute probable migraine were only eligible if their reason for not meeting full migraine criteria was insufficient number of total lifetime headaches or prolonged duration of headache (72 h) | • Secondary headache • Receiving a lumbar puncture in the ED • Temperature ≥100.4°F • Having a new neurologic abnormality, seizure disorder • Concurrent use of study drugs / monoamine oxidase inhibitor / immunesuppressives • Pregnancy, lactation • Previous enrollment • Allergy • Intolerance • Contraindication to the study drugs, including hepatic dysfunction, peptic ulcer | Acute attack | Metoclopramide 10 mg IV (110 patients) Ketorolac 30 mg IV (110 patients) Valproate 1 g IV (110 patients) | Baseline 1 h | NRS & Descriptive ordinal scale | Two in metoclopramide gp Two in ketorolac gp Three in valproate gp All of them took preventive migraine medication | International Headache Society’s International Classification of Headache Disorders, second edition 2004 | Authors couldn’t identify a clear vision; however, they thought that valproate was the least effective while metoclopramide was better than ketorolac in decrease pain of acute migraine attack |
All drugs were IV over 15 min | |||||||||||
Talabi et al. 2013 [30] | Iran | Double blinded RCT | • Age: 20–60 years old • Presented with acute headache similar to previous episodes with or without phonophobia, photophobia, vomiting, or nausea | • Fever • Neck stiffness • Altered mental state • Pregnancy • Hypertension • Recent trauma or seizure (within 24 h) • Focal neurological abnormality on physical examination • Allergy to metoclopramide • Cardiovascular diseases • Taking triptan or ergot during the last 24 h | Acute attack | Metoclopramide 20 mg IV Infused over 15 min (62 patients) Sumatriptan 6 mg SC (62 patients) | Baseline 1 h | VAS | -- | International Headache Society (IHS) | Authors conclude that metoclopramide could significantly decrease pain intensity of acute attack of migraine (p < 0.001) |
Salazar-Zúñiga et al. 2006 [29] | México | RCT | • Age: 18 to 65, of either sex • Moderate to severe intensity • With or without aura • Without restriction in time of evolution of the migraine • History of one to six attacks in 1 month | • Fever prior to pain • Use of psychotropic drugs, tobacco or alcohol in the last 24 h • Coronary disease • Recent trauma, meningism • Three months previous use of drugs: (barbiturate, antihypertensive, antiparkinsonian, antihistamine, anticholinergic) • Morbid obesity | Acute attack | Metoclopramide 10 mg IV Slowly infusion over 3–5 min (60 patients) Sumatriptan 6 mg SC Slowly (60 patients) | Baseline 15 min 30 min 45 min 1 h | Headache intensity scale; 0 = no headache 1 = mild 2 = moderate 3 = intense | -- | International Headache Society criteria for migraine 2004 | Authors conclude that metoclopramide could significantly decrease pain more than sumatriptan only at 15 min (p < 0.01) |
Cicek et al. 2004 [34] | Turkey | Prospective double blinded RCT | Having ≥4 symptoms of vascular score criteria: • Aura or anticipation of H/A, nausea, vomiting, diarrhea, anorexia • Unilateral / Periodical / Throbbing headache • Photophobia / phonophobia • Visual complaints • Childhood onset H/A • History of motion sickness • FH of headache • Headache triggered by certain foods • Temporal association with menstruation | • Secondary headache • Altered mental status • Abnormal vital signs • Pregnant • History of epilepsy • Parkinson • Pheochromacytoma • Known allergy to the study drugs | Acute attack | Metoclopramide 10 mg IV + Placebo IM (85 patients) Placebo IV + Placebo IM (83 patients) Pethidine 50 mg IM + Placebo IV (84 patients) Metoclopramide 10 mg IV + Pethidine 50 mg IM (84 patients) | Baseline 15 min 30 min 45 min | VAS | -- | Vascular score criteria | Metoclopramide had the same effect as the combination (p = 1) Also, metoclopramide alone or the combination could significantly decrease pain more than pethidine alone (p = 0.038) |
Cete et al. 2005 [19] | Turkey | Prospective double blinded RCT | • Nonconsecutive sample of patients who presented to the ED with headache, meeting International Headache Society criteria for migraine | • Age <18 years old • A known adverse reaction to metoclopramide or MgSO4 • Consumption of the study drugs within 48 h • Temperature of ≥ 38 • Altered mental status, meningeal signs • Renal or cardiac disease | Acute attack | Metoclopramide 10 mg IV + normal saline 100 ml (37 patients) Normal saline 100 ml (40 patients) MgSO4 2 g + normal saline 100 ml (36 patients) | Baseline 15 min 30 min | VAS | -- | International Headache Society criteria 1988 | At both 15 and 30 min: All drugs could significantly decrease pain (p < 0.001); however, the difference between them was non-significant (0.619) |
All drugs infused over 10 min | |||||||||||
Jones et al. 1996 [21] | US | Prospective double blinded RCT | • Age: ≥ 16 years old • Had normal ability to communicate • Had one or more of the following: - Recurrent headaches preceded by neurological symptoms - Recurrent throbbing headaches that were at least initially unilateral - Recurrent throbbing headaches consistently associated with significant nausea or vomiting, photophobia, sonophobia, or mood changes | • Age >60 years • A known intolerance to study drugs • Using drugs that cause extrapyramidal reactions • Pregnancy or lactation • History of drug-seeking behavior • Lack of responsible person available to care for and transport the patient when departing from the ED • Secondary causes of H/A e.g. neurological or seizure disorder, toxic exposure, alcohol abuse, vascular disease, recent trauma, hypertension, or hepatic or renal failure | Acute attack | Metoclopramide 10 mg IM (29 patients) Normal saline 2 ml IM (29 patients) Prochlorperazine 10 mg IM (28 patients) | Baseline 1 h | VAS | many pts use drugs before presentation into ED | International Headache Society classification 1988 | Authors conclude that prochlorperazine could significantly decrease pain more than metoclopramide (p < 0.01) |
Coppola et al. 1995 [15] | Texas | Prospective double blinded RCT | • Age 18–65 years old • Presentation to the ED with migraine headache as defined by the Ad Hoc Committee on Classification of Headache • Patients were enrolled if they presented with cephalgia similar to previous episodes, with or without nausea, vomiting, photophobia, or phonophobia | • Fever or meningismus • Altered mental state • Recent (within 24 h) use of analgesics, drugs, or alcohol • pregnancy • Oxygen saturation less than 90% • Recent trauma or seizure (within 24 h) • First episode of headache • Suspicion of intracranial process requiring further investigation (eg, SAH, space-occupying lesion) • Allergy to study drugs • Diastolic BP >90 mm Hg | Acute attack | Metoclopramide 10 mg IV (24 patients) Normal saline 2 ml IV (24 patients) Prochlorperazine 10 mg IV (22 patients) | Baseline 30 min | VAS | -- | Ad Hoc Committee on Classification of Headache 1962 | Authors conclude that there was non-significant difference between drugs in decreasing pain of acute migraine attack (p = 0.15) |
Cameron et al. 1995 [33] | London | Prospective double blinded RCT | • Aged 17–60 years old • Presenting to hospital ED, diagnosed as having acute migraine headache by the attending physician • Diagnosis of migraine either with or without aura, as defined by the International Headache society 1988 • Patients taking opioids were not excluded | • First migraine or nonmigraine headache • More than six prior headaches per month • Allergy to study drugs • Present use of phenothiazine, isoniazid, monoamine oxidase (MAO) inhibitor, or cyclic antidepressant • Parkinson’s disease or a past history of dystonic reactions • Seizure disorder • Age <17 or >60 years • Pregnancy or lactation • Lack of transportation home / no person to care for the patient at home • Lack of consent | Acute attack | Metoclopramide 0.1 mg/kg IV (44 patients) Chlorpromazine 0.1 mg/kg IV (47 patients) Both drugs diluted to a concentration of 2.5 mg/ml | Baseline 45 min | VAS | No prior use of ttt Or Taking acetaminophen/ aspirin / NSAID failure | criteria of International Headache society 1988 | Authors conclude that there was non-significant difference between drugs in decreasing pain of acute migraine attack (p = 0.35) |
(10/34) Pts taking codeine preparations / oxycodone and (5/16) pts taking butalbital preparation failed to respond to ttt | |||||||||||
Ellis et al. 1993 [36] | US | double blinded RCT | • Age: ≥ 18 years old • Normal ability to communicate • Had one or more of the following characteristics: - recurrent H/A that were at least initially unilateral /proceeded by neurologic symptoms - recurrent throbbing H/A that consistently associated with significant nausea or vomiting, or associated with mood changes, and photophobia | • Taking monoamine-oxidase inhibitors • History of pheochromocytoma or epilepsy • Receiving other drugs likely to cause extrapyramidal reactions • Pregnant and breast-feeding | Acute attack | Metoclopramide 10 mg IV + Placebo oral (10 patients) Placebo oral + Placebo IV (10 patients) Ibuprofen 600 mg oral + Placebo IV (10 patients) Metoclopramide 10 mg IV + Ibuprofen 600 mg oral (10 patients) | Baseline 30 min 1 h | VAS | -- | -- | Metoclopramide could significantly decrease pain more than ibuprofen at both 30 min and 1 h. (p = 0.04, p = 0.01 respectively) However, the difference between metoclopramide and the combination wasn’t significant |
Tek et al. 1990 [18] | California | Prospective double blinded RCT | • Diagnosis of migraine was made by physicien if the patient had a periodic headache with a throbbing component • Presence of at ≥1 of the following symptoms: photosonophobia, nausea or vomiting, unilaterality, strong FH, onset in adolescence, or history of relief with ergot • The history of aura combined with the above criteria differentiated the headache as a classic (VS common) migraine | • Age: <18 or >60 years • First episode of headache • Sudden onset of headache • History of recent trauma or seizure • Fever, meningismus, • Altered mental status • Focal neurological abnormality • Primary diagnosis other than migraine • Having any contraindication to the study drug | Acute attack | Metoclopramide 10 mg IV (24 patients) Normal saline 2 ml IV (26 patients) | Baseline 1 h | Relief score / numeric scale | -- | Ad Hoc Committee on Classification of Headaches 1962 | Authors conclude that metoclopramide could significantly obtain pain relief (p < 0.02) |
Tfelt-Hansen et al. 1980 [22] | Denmark | Double blinded RCT | • The trial involved 150 patients with classical or common migraine as defined by the Ad Hoc Committee on Classification of Headache • They fulfilled the criteria suggested by Olesen • Patients presented themselves with a migraine attack at the acute migraine clinic in Copenhagen • Patients with marked nausea or vomiting were selected | Acute attack | Metoclopramide 10 mg IM + Placebo suppository (49 patients) Placebo IM + Placebo suppository (51 patients) Metoclopramide 20 mg suppository + Placebo IM (50 patients) | Baseline 1 h | Rating scale of headache | -- | Ad Hoc Committee on Classification of Headache 1962 | Authors conclude that metoclopramide couldn’t significantly decrease pain either IM or suppository (p = 0.06) | |
All patients were given paracetamol (aceteminophen) 1 g and diazepam 5 mg orally | |||||||||||