Clemencia Solorzano

A trial of metoclopramide vs sumatriptan for the emergency department treatment of migraines

Objective: To compare the efficacy of 20 mg of IV metoclopramide, given up to four times over 2 hours as needed for persistent headache, with 6 mg of subcutaneous sumatriptan for the emergency department treatment of migraine headaches. Methods: This was a randomized, double-blind, clinical trial with two intervention arms. The primary endpoint was change in pain intensity as measured by an 11-point pain scale at 2 hours. Secondary endpoints included change in pain intensity at 24 hours and rates of pain-free headache relief at 2 and 24 hours. Results: Two hundred two patients were screened, and 78 of 91 eligible patients were randomized. The two groups had comparable pain scores at baseline. By 2 hours, the change in pain intensity for the metoclopramide group was 7.2 compared with 6.3 for the sumatriptan group (95% CI for difference: −0.2 to 2.2). When compared at 24 hours, the metoclopramide group had improved by 6.1 compared with baseline and the sumatriptan group had improved by 5.0 (95% CI for difference: −0.6 to 2.8). At 2 hours, pain-free rates were 59% in the metoclopramide arm and 35% in the sumatriptan arm (95% CI for difference of 24%: 2 to 46%). The most common side effects at both time points were weakness, dizziness, and drowsiness, which were distributed evenly between the two groups. There were no reports of chest pain within the first 2 hours. The incidence of restlessness, stiffness, and abnormal movements was distributed equally between the two groups. Conclusions: When compared at 2 and 24 hours, aggressive (20 mg dosed up to four times) IV metoclopramide and 6 mg of subcutaneous sumatriptan relieved migraine headache pain comparably. Some secondary endpoints suggest that metoclopramide may be the preferable therapy for migraines presenting to the emergency department.

Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine

Objective: We compared the efficacy of IV valproate with metoclopramide and with ketorolac in patients presenting to an emergency department (ED) with acute migraine. Methods: This was a double-blind comparative efficacy trial. Patients were randomized to 1,000 mg sodium valproate, 10 mg metoclopramide, or 30 mg ketorolac, each administered as an IV drip over 15 minutes. The primary outcome was improvement in headache by 1 hour, measured on a verbal 0 to 10 scale, at baseline and 60 minutes later. Important secondary outcomes included (1) need for rescue medication in the ED, and (2) sustained headache freedom. Results: Three hundred thirty patients were enrolled over 30 months beginning in October 2010. Baseline characteristics were comparable among the 3 arms. On the primary outcome, patients receiving IV valproate improved by a mean of 2.8 (95% confidence interval [CI]: 2.3, 3.3) on the 0 to 10 scale; those receiving IV metoclopramide improved by 4.7 (95% CI: 4.2, 5.2); and those receiving IV ketorolac improved by 3.9 (95% CI: 3.3, 4.5). On the secondary endpoints, 69% (95% CI: 60%, 78%) of patients receiving valproate required rescue medication, compared with 33% (95% CI: 24%, 42%) of metoclopramide patients and 52% (95% CI: 42%, 63%) of those assigned to ketorolac. Sustained headache freedom was achieved in 4% (95% CI: 0%, 7%) of those randomized to valproate, 11% (95% CI: 5%, 17%) of metoclopramide patients, and 16% (95% CI: 9%, 23%) receiving ketorolac. In the metoclopramide arm, 6% (95% CI: 3%, 12%) of patients reported feeling “very restless” after investigational medication administration. Conclusions: Valproate was less efficacious than either metoclopramide or ketorolac. Metoclopramide demonstrated superiority to ketorolac on several endpoints. Classification of evidence: This study provides Class I evidence that in ED patients with acute migraine, IV valproate is inferior to metoclopramide or ketorolac in improving headache outcomes.

A randomized placebo-controlled trial of single-dose IM corticosteroid for radicular low back pain.

Study Design. A randomized, double-blind, placebo-controlled trial of patients with radicular low back pain who present to an emergency department (ED) within 1 week of pain onset. Objective. We hypothesized that a single intramuscular 160 mg dose of methylprednisolone acetate would improve pain and functional outcomes 1 month after ED discharge if the corticosteroid were administered early in disease symptomotology. Summary of Background Data. Parenteral corticosteroids are not recommended for acute, radicular low back pain, though their role in this disease process is ill-defined. To date, this medication class has only been studied in a highly selected group of patients requiring hospitalization. Methods. Adults between the ages of 21 and 50 who presented to an ED with low back pain and a positive straight leg raise test were enrolled. The primary outcome was change in pain intensity on an 11 point numerical rating scale 1 month after ED visit. Secondary outcomes 1 month after ED discharge included analgesic use, functional disability, and adverse medication effects. Results. Six hundred thirty-seven patients were approached for participation, 133 were eligible, and 82 were randomized. Baseline characteristics were comparable between the groups. The primary outcome, a comparison of the mean improvement in pain intensity, favored methylprednisolone by 1.3 (P = 0.10). Some secondary outcomes favored methylprednisolone, such as use of analgesic medication within the previous 24 hours (22% vs. 43%, 95% CI for difference of 20%: 0%–40%) and functional disability (19% vs. 49%, 95% CI for difference of 29%: 9%–49%). Adverse medication effects 1 week after ED discharge were reported by 32% of methylprednisolone and 24% of placebo patients (95% CI for difference of 9%: −12% to 30%). Conclusion. This study was a negative study, though there was a suggestion of benefit of methylprednisolone acetate in a population of young adults with acute radicular low back pain. Further work with a larger sample of patients is needed.

Metoclopramide for Acute Migraine: A Dose-Finding Randomized Clinical Trial

STUDY OBJECTIVE Intravenous metoclopramide is effective as primary therapy for acute migraine, but the optimal dose of this medication is not yet known. The objective of this study is to compare the efficacy and safety of 3 different doses of intravenous metoclopramide for the treatment of acute migraine. METHODS This was a randomized, double-blind, dose-finding study conducted on patients who presented to our emergency department (ED) meeting International Classification of Headache Disorders criteria for migraine without aura. We randomized patients to 10, 20, or 40 mg of intravenous metoclopramide. We coadministered diphenhydramine to all patients to prevent extrapyramidal adverse effects. The primary outcome was improvement in pain on an 11-point numeric rating scale at 1 hour. Secondary outcomes included sustained pain freedom at 48 hours and adverse effects. RESULTS In this study, 356 patients were randomized. Baseline demographics and headache features were comparable among the groups. At 1 hour, those who received 10 mg of intravenous metoclopramide improved by a mean of 4.7 numeric rating scale points (95% confidence interval [CI] 4.2 to 5.2 points); those who received 20 mg improved by 4.9 points (95% CI 4.4 to 5.4 points), and those who received 40 mg improved by 5.3 points (95% CI 4.8 to 5.9 points). Rates of 48-hour sustained pain freedom in the 10-, 20-, and 40-mg groups were 16% (95% CI 10% to 24%), 20% (95% CI 14% to 28%), and 21% (95% CI 15% to 29%), respectively. The most commonly occurring adverse event was drowsiness, which impaired function in 17% (95% CI 13% to 21%) of the overall study population. Akathisia developed in 33 patients. Both drowsiness and akathisia were evenly distributed across the 3 arms of the study. One month later, no patient had developed tardive dyskinesia. CONCLUSION Twenty milligrams or 40 mg of metoclopramide is no better for acute migraine than 10 mg of metoclopramide.

Treating Headache Recurrence After Emergency Department Discharge: A Randomized Controlled Trial of Naproxen Versus Sumatriptan

STUDY OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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 patients previous experience with the medication.

A clinical trial of trimethobenzamide/diphenhydramine versus sumatriptan for acute migraines.

Background.—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.

A Randomized Trial of Diphenhydramine as Prophylaxis Against Metoclopramide-Induced Akathisia in Nauseated Emergency Department Patients

STUDY OBJECTIVE Akathisia, an adverse effect observed at times after administration of parenteral metoclopramide, is an unpleasant symptom complex characterized by restlessness and agitation. Some try to limit the development of akathisia by coadministering diphenhydramine when using parenteral metoclopramide. The goal of this investigation is to determine whether concomitant administration of diphenhydramine 25 mg decreased the rate of development of akathisia after administration of 10 mg or 20 mg of intravenous metoclopramide. METHODS This was a randomized, double-blind, factorial design trial. Patients who presented to our emergency department with a primary or secondary chief complaint of nausea were randomized to one of the following 4 groups: (1) metoclopramide 10 mg+diphenhydramine 25 mg; (2) metoclopramide 10 mg+placebo; (3) metoclopramide 20 mg+diphenhydramine 25 mg; (4) metoclopramide 20 mg+placebo. The medications were inserted into a 50-mL bag of normal saline solution and administered as an intravenous drip during 15 minutes. Primary outcome was development of akathisia within 60 minutes of medication administration, as measured by blinded assessors using a short akathisia instrument, or use of rescue medication for treatment of akathisia by blinded clinical staff. Patients were also asked at baseline and 30 minutes later whether they felt restless. RESULTS Two hundred eighty-nine patients were randomized and 286 patients were included in the final analysis. Within 1 hour of medication administration, 17 of 143 patients randomized to diphenhydramine (12%; 95% confidence interval [CI] 8% to 18%) and 17 of 143 (12%; 95% CI 8% to 18%) randomized to placebo developed akathisia (95% CI for difference of 0%: -8% to 8%). Thirteen of 143 patients randomized to metoclopramide 10 mg (9%; 95% CI 5% to 15%) and 21 of 143 randomized to metoclopramide 20 mg (15%; 95% CI 10% to 22%) developed akathisia (95% CI for difference of 6%: -2% to 14%). In those administered prophylactic diphenhydramine, odds of akathisia relative to placebo were 1.0 (95% CI 0.5 to 2.0). Odds of akathisia in those administered 20 mg of metoclopramide relative to the 10-mg dose were 1.7 (95% CI 0.8 to 3.6). Among patients who received 20 mg of metoclopramide, subjective restlessness was reported by 7 of 72 (9.7%) patients who received diphenhydramine and 14 of 71 (19.7%) patients who received placebo (95% CI for difference of 10%: -2% to 22%). CONCLUSION Routine prophylaxis with diphenhydramine to prevent akathisia is unwarranted when intravenous metoclopramide is administered over 15 minutes. For patients administered 20 mg of metoclopramide, prophylactic diphenhydramine may decrease subjective restlessness.

Effect of Risedronate on Bone in Renal Transplant Recipients

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.

A Randomized Trial of Intravenous Ketorolac Versus Intravenous Metoclopramide Plus Diphenhydramine for Tension-Type and All Nonmigraine, Noncluster Recurrent Headaches

STUDY OBJECTIVE 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. METHODS 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 patients desire to receive the same medication again. RESULTS 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. CONCLUSION 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.

Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial.

STUDY OBJECTIVE More than 1 million patients present to US emergency departments (EDs) annually seeking care for acute migraine. Parenteral antihistamines have long been used in combination with antidopaminergics such as metoclopramide to treat acute migraine in the ED. High-quality data supporting this practice do not exist. We determine whether administration of diphenhydramine 50 mg intravenously+metoclopramide 10 mg intravenously results in greater rates of sustained headache relief than placebo+metoclopramide 10 mg intravenously. METHODS This was a randomized, double-blind, clinical trial comparing 2 active treatments for acute migraine in an ED. Eligible patients were adults younger than 65 years presenting with an acute moderate or severe headache meeting International Classification of Headache Disorders-2 migraine criteria. Patients were stratified according to presence or absence of allergic symptoms. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining this level of relief without use of any additional headache medication for 48 hours. Secondary efficacy outcomes included mean improvement on a 0 to 10 verbal scale between baseline and 1 hour, the frequency with which subjects indicated they would want the same medication the next time they present to the ED with migraine, and the ED throughput time. Sample size calculation using a 2-sided α of .05, a β of .20, and a 15% difference between study arms determined the need for 374 patients. An interim analysis was conducted when data were available for 200 subjects. RESULTS Four hundred twenty patients were approached for participation. Two hundred eight eligible patients consented to participate and were randomized. At the planned interim analysis, the data and safety monitoring board recommended that the study be halted for futility. Baseline characteristics were comparable between the groups. Fourteen percent (29/208) of the sample reported allergic symptoms. Of patients randomized to diphenhydramine, 40% (40/100) reported sustained relief at 48 hours, as did 37% (38/103) of patients randomized to placebo (95% confidence interval [CI] for difference of 3%: -10% to 16%). One hour after medication administration, patients randomized to diphenhydramine improved by a mean of 5.1 on the 0 to 10 scale versus 4.8 for those randomized to placebo (95% CI for difference of 0.3: -0.6 to 1.1). Eighty-five percent (84/99) of the patients in the diphenhydramine arm reported they would want the same medication combination during a subsequent ED visit, as did 76% (77/102) of those who received placebo (95% CI for difference of 9%: -2% to 20%). Median ED length of stay was 122 minutes (interquartile range 84 to 180 minutes) in the diphenhydramine group and 139 minutes (interquartile range 90 to 235 minutes) in the placebo arm. Rates of adverse effects, including akathisia, were comparable between the groups. CONCLUSION Intravenous diphenhydramine, when administered as adjuvant therapy with metoclopramide, does not improve migraine outcomes.