D2 dopamine receptor-mediated mechanisms of dopaminergic system modulation in in vivo and in vitro experimental models of migraine.

The dopaminergic system is implicated in the pathophysiology of migraine. However, the underlying mechanisms remain unclear. We explored the effects and mechanisms of dopaminergic system modulation in the in vivo and in vitro rat models of migraine. Dopaminergic agonist apomorphine, D2 receptor antagonists metoclopramide and haloperidol and 5-HT3 receptor antagonist ondansetron alone and together were tested in nitroglycerin-induced migraine model, in vivo. Likewise, the combinations of drugs were also tested on basal calcitonin gene-related peptide (CGRP) release in vitro hemiskull preparations. Mechanical allodynia was tested by von Frey filaments. CGRP concentrations in trigeminovascular structures and in vitro superfusates and c-Fos levels in the brainstem were determined by enzyme-linked immunosorbent assay. Meningeal mast cells were evaluated with toluidine blue staining. Apomorphine further enhanced nitroglycerin-induced mechanical allodynia, brainstem c-fos expression, trigeminal ganglion and brainstem CGRP concentrations and meningeal mast cell degranulation, in vivo. Haloperidol completely antagonised all apomorphine-induced effects and also alleviated changes induced by nitroglycerin without apomorphine. Metoclopramide and ondansetron partially attenuated apomorphine- or nitroglycerin-induced effects. A combination of haloperidol and ondansetron decreased basal CGRP release, in vitro, whereas the other administrations were ineffective. Apomorphine-mediated dopaminergic activation exacerbated nitroglycerin-stimulated nociceptive reactions by further enhancing c-fos expression, CGRP release and mast cell degranulation in strategical structures associated with migraine pain. Metoclopramide partially attenuated the effects of apomorphine, most likely because it is also a 5-HT3 receptor antagonist. Haloperidol with pure D2 receptor antagonism feature appears to be more effective than metoclopramide in reducing migraine-related parameters in dopaminergic activation- and/or NTG-induced migraine-like conditions.

Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.

Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.

Pheochromocytoma crisis with refractory Acute Respiratory Distress Syndrome (ARDS), Takotsubo syndrome, emergency adrenalectomy, and need for Extracorporeal Membrane Oxygenation (ECMO) in a previously undiagnosed and asymptomatic patient, due to the use of metoclopramide.

BACKGROUND: Pheochromocytoma (PCC) crisis is a rare life-threatening endocrine emergency. The diagnosis and treatment of PCC crisis, with acute respiratory distress syndrome (ARDS) as the first manifestation, is highly challenging, and traditional PCC management strategies are no longer suitable for these patients. CASE PRESENTATION: A 46-year-old female patient was admitted to the Intensive Care Unit (ICU) following sudden-onset acute respiratory distress and subsequent initiation of mechanical ventilation via endotracheal intubation. She was initially suspected of having a PCC crisis through the bedside critical care ultrasonic examination protocol. The computed tomography examination revealed a left adrenal neoplasm of 6.5cm × 5.9cm. The plasma-free metanephrine level was 100 times higher than the reference value. These findings were compatible with her PCC diagnosis. Alpha-blockers and fluid intake were started immediately. The endotracheal intubation was removed on the 11th day after admission to the ICU. The patient progressed to severe ARDS again, and invasive ventilation and continuous renal replacement therapy were needed. Despite aggressive therapy, her condition deteriorated. Therefore, she underwent veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-assisted emergency adrenalectomy after multidisciplinary discussion. Postoperatively, the patient was supported by VA-ECMO for 7days. She was discharged from the hospital on day 30 after tumor resection. CONCLUSIONS: This case highlighted the challenges in diagnosing and managing ARDS associated with PCC crisis. The traditional preoperative preparation protocol and optimal operation timing for patients with PCC are not suitable for patients with PCC crisis. Patients with life-threatening PCC crisis may benefit from early tumor removal, and VA-ECMO could maintain hemodynamic stability during and after surgery.

The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Risk of Adverse Events Associated with Domperidone and Metoclopramide in Gastroparesis: Systematic Review and Meta-analysis.

BACKGROUND: Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate the profile of adverse events (AEs) of dopamine antagonists used in the treatment of children and adults with gastroparesis. METHODS: We searched EMBASE and MEDLINE up to March 25, 2021, for relevant clinical trials and observational studies. We conducted a proportional meta-analysis to estimate the pooled occurrence of AEs (%), with 95% confidence interval (CI), from arm-level data across studies and the comparative occurrence of AEs from placebo-controlled clinical trials (odds ratio [OR] with 95% CI). RESULTS: We identified 28 studies assessing AEs experienced by patients treated for gastroparesis with domperidone and metoclopramide; 22 studies contributed data to the meta-analyses. Cardiovascular, neurological, and endocrine AEs were commonly observed, with point incidences varying from 1 to > 50%. Clinically important AEs, such as QTc prolongation, occurred in 5% of patients treated with domperidone (95% CI: 3.32-8.62). Restlessness, an extrapyramidal AE, occurred in 15% of patients (95% CI: 7.48-26.61) treated with metoclopramide, with a 7-fold increase compared with patients receiving placebo (OR: 7.72; 95% CI: 1.27-47.05). Variation in terminology to describe extrapyramidal events precluded further pooled analyses. Additional meta-analyses were not feasible due to discrepancies in the assessment and reporting of the AEs. CONCLUSIONS: The evidence confirms concerns of cardiovascular, extrapyramidal, and endocrine AEs in patients with gastroparesis treated with domperidone and metoclopramide. Imprecise AE reporting limits firm interpretation and conclusions. REGISTRATION: PROSPERO international prospective register of systematic reviews (registration number: CRD42021248888).

Adjuvant anticholinergic therapy for the prevention of akathisia in patients with primary headache in the emergency department: A systematic review.

OBJECTIVES: Adjunct therapy with anticholinergic agents has been proposed to reduce the incidence of extrapyramidal side effects such as akathisia following treatment with neuroleptics or metoclopramide. This systematic review assessed the effectiveness of anticholinergic agents to prevent neuroleptic or metoclopramide-induced akathisia in patients presenting to the emergency department (ED) with benign headache. METHODS: Eight electronic databases and the gray literature were searched to identify randomized controlled trials involving adult patients presenting to the ED with primary headache treated with neuroleptic or metoclopramide. Study selection, data extraction, and quality assessment were completed by two independent reviewers. Individual or pooled meta-analysis of dichotomous outcomes were calculated as relative risks (RRs) with 95% confidence intervals (CIs) using a random-effects model. Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 1032 studies were screened, of which two studies were included in the review. Both studies provided patients with diphenhydramine following treatment with neuroleptics or metoclopramide. Treatment with diphenhydramine did not reduce the incidence of akathisia compared to treatment with placebo (RR 0.83, 95% CI 0.43-1.61, I2  = 0%). The impact of diphenhydramine on pain relief, need for rescue medications, and relief of other extrapyramidal side effects was reported in one of the two studies, with no significant differences noted in any outcomes compared to patients treated with placebo. CONCLUSION: This review found insufficient evidence to recommend the use of diphenhydramine as an adjunct therapy to prevent akathisia in ED patients treated with neuroleptics or metoclopramide for primary headache. This finding relies on the results of two small randomized controlled trials with incomplete outcome reporting. Additional high-quality studies are needed to better understand the clinical efficacy of agents with anticholinergic properties in the ED management of patients with primary headaches.

Effectiveness and safety of metoclopramide in treatment of intractable hiccup: a protocol of systematic review and meta-analysis.

INTRODUCTION: Hiccup is a common disease that not only occurred on adults but also on infants, which can severely do harm to patients' physical and psychological health. Metoclopramide has been reported to have effects on intractable hiccup. However, there is a limited evidence that describes the efficacy and safety of metoclopramide in the treatment of intractable hiccup. The aim of this article is to obtain evidence on the effectiveness and safety of metoclopramide in treating patients with intractable hiccup. METHODS AND ANALYSIS: We will search the following databases, including PubMed, Cochrane Library, Embase, Web of Science, CBM, Wan-fang, VIP database, CNKI and MEDLINE from their inception to 11 November 2021. All the randomised controlled trials associated with metoclopramide in treating intractable hiccup will be included. Articles screened, selected and extracted will be performed by two researchers independently. The risk of bias will be assessed by using the Cochrane Collaboration. We will carry out the meta-analysis by using RevMan V.5.4 software. PROSPERO REGISTRATION NUMBER: CRD42021293000.

Prolonged extrapyramidal symptoms induced by long-term, intermittent administration of low-dose olanzapine along with metoclopramide for emesis: A case report.

BACKGROUND: Antipsychotics with dopamine (D2) receptor antagonism can be effective for emesis in cancer patients. Extrapyramidal symptoms (EPS) induced by typical antipsychotics can be exacerbated by other D2 receptor antagonists. We describe a case of persistent EPS induced by long-term, intermittent administration of low-dose olanzapine along with metoclopramide for emesis. CASE PRESENTATION: A 59-year-old pancreatic cancer patient underwent chemotherapy for 7 months. He was referred to the psychiatry department because of restlessness and insomnia. Although he did not have obvious depressive symptoms, he was anxious about the cancer treatment. For chemotherapy-induced nausea, he had been prescribed 5 mg of olanzapine intermittently for 7 months. He had last used the drug 9 days before presenting it to us. Additionally, he received metoclopramide and palonosetron as antiemetics. We considered akathisia and cancer-related anxiety/agitation as possible causes of restlessness and insomnia, and prescribed clonazepam. However, his symptoms worsened, resulting in hospitalization. We reconsidered his symptoms as cancer-related anxiety/agitation and prescribed quetiapine. Although it was effective, he had tremors and was assessed by a neurologist. Considering the clinical manifestations of rigidity, postural reflex disorder, and a mask-like face, we suspected drug-induced parkinsonism and replaced quetiapine with biperiden on the next day, leading to his discharge after 2 weeks. He did not have symptom recurrence even after discontinuation of biperiden. CONCLUSIONS: Long-term, intermittent administration of low-dose antipsychotics with other antiemetics having D2 receptor antagonism can cause prolonged EPS. Especially in cancer patients, who often require polypharmacy, clinicians should consider exacerbated adverse effects due to drug interactions.

A randomized trial of ketorolac and metoclopramide for migraine in the emergency department.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of a common monotherapy (intravenous [iv] metoclopramide) compared to a combination strategy (adding iv ketorolac to metoclopramide) in children presenting for acute treatment of migraine headache in the emergency department (ED). METHODS: Children aged 5-17 years presenting for acute treatment of migraine headache at two pediatric EDs were enrolled in a double-blind randomized controlled trial. Children were randomly assigned to receive iv metoclopramide 0.2 mg/kg) and placebo or iv metoclopramide (0.2 mg/kg) and ketorolac (0.5 mg/kg). The primary outcome was a mean change in pain from baseline to 120 min via a 100 mm Visual Analog Scale (VAS). Follow-up was conducted 24-h after discharge. RESULTS: Fifty-three children were randomized and included in the analysis (monotherapy group [metoclopramide + placebo], n = 27; and ketorolac group [metoclopramide + ketorolac], n = 26); mean age was 12.9 ± 2.7 years and baseline pain severity on VAS was 67.3 ± 2.7 mm. The mean change in pain intensity at 120 min was -44 mm (SD: 24; 95% confidence interval [CI]: 32-57) for the monotherapy group and -36 mm (SD: 24; 95% CI: 23-49) for the ketorolac group, with a mean difference between groups of 8 mm (95% CI: -9-25; p = 0.360). Seventeen percent of the children (9/53; 95% CI: 7-27%) were pain-free at discharge. There was no difference in headache recurrence or adverse events between groups. CONCLUSIONS: The approach of combining iv metoclopramide with ketorolac failed to improve pain scores in children presenting for acute treatment of migraine headache in the ED compared to metoclopramide monotherapy. Most patients were discharged with residual pain. Further comparative studies are needed to test alternative ED treatments for migraine in children or adolescents.

Prophylactic antiemetics for adults receiving intravenous opioids in the acute care setting.

BACKGROUND: Physicians often prescribe opioids for pain in the acute care setting. Nausea and vomiting are well-described adverse events, occurring in over one-third of patients. Prophylactic antiemetics may be one option to reduce opioid-associated nausea and vomiting. However, these medications also have their own adverse effects, so it is important to understand their efficacy and safety prior to routine use. This is a review of randomized controlled trials comparing prophylactic antiemetics versus placebo or standard care for preventing opioid-associated nausea and vomiting. OBJECTIVES: To assess the effects of prophylactic antiemetics for nausea and vomiting in adults (aged 16 years or older) receiving intravenous opioids in the acute care setting. SEARCH METHODS: We searched CENTRAL (the Cochrane Library), MEDLINE (OVID), Embase (OVID) from inception to January 2022, and Google Scholar (17 January 2022). We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and screened reference lists. SELECTION CRITERIA: We included randomized controlled trials of prophylactic antiemetics versus placebo or standard care in adults prior to receiving an intravenous opioid. DATA COLLECTION AND ANALYSIS: Two review authors (MG, JNC) independently determined the eligibility of each study according to the inclusion criteria. Two review authors (MG, GDP) then independently extracted data, assessed risk of bias, and determined the certainty of evidence using GRADE. Our primary outcomes were the occurrence of nausea, vomiting, and adverse events. Secondary outcomes included nausea severity, number of vomiting episodes, and number of participants requiring antiemetic rescue therapy. We presented outcomes as risk ratios (RR) for dichotomous data (e.g. presence of vomiting, presence of nausea, number of participants requiring rescue medication, adverse events) and mean difference (MD) or standardized mean difference for continuous data (e.g. number of vomiting episodes, nausea severity) with 95% confidence intervals (CI). MAIN RESULTS: We included three studies involving 527 participants (187 women and 340 men) with a mean age of 42 years.  All studies used intravenous metoclopramide (10 mg) as the intervention and a placebo for the comparator. No studies assessed any other antiemetic or compared the intervention to standard care. Compared to placebo, metoclopramide did not reduce vomiting (RR 1.18, 95% CI 0.26 to 5.32; low-certainty evidence) or nausea (RR 0.55; 95% CI 0.15 to 2.03; low-certainty evidence) and there was no difference in adverse events (RR 2.34, 95% CI 0.47 to 11.61; low-certainty evidence).  No data were available regarding the number of vomiting episodes. Metoclopramide did reduce the severity of nausea compared with placebo (MD -0.49, 95% CI -0.75 to -0.23; low-certainty evidence) but did not reduce the need for rescue medication (RR 1.86, 95% CI 0.17 to 20.16; low-certainty evidence).  Two studies were at unclear risk of bias for random sequence generation, one for blinding of outcome assessors, one for incomplete outcome data, and two for selective reporting. The studies were at low risk of bias for all remaining components. AUTHORS' CONCLUSIONS: There was no evidence that prophylactic metoclopramide affected the risk of vomiting, nausea, or the need for rescue medication when provided prior to intravenous opioids in the acute care setting. There was a clinically insignificant difference in nausea severity when comparing prophylactic metoclopramide with placebo. Overall, the evidence was of low certainty. Future research could better delineate the effects of prophylactic antiemetics on specific populations, and new studies are needed to evaluate the use of other prophylactic antiemetic agents, for which there were no data.

A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH).

OBJECTIVE: The objective of the study is to explore the long-term effectiveness and tolerability of metoclopramide in the treatment of CIH. METHOD: This study is a retrospective, observational cohort study of patients prescribed metoclopramide for CIH at the South London & Maudsley (SLaM) NHS Foundation Trust. RESULTS: Of the 96 patients identified, 14 patients were eligible for inclusion in our study. Five patients continued treatment with a mean duration of 27 months (SD = 17.8), and one patient continued until transfer with a duration of 3 months. Eight patients discontinued treatment after a mean duration of 8 months. CONCLUSION: Metoclopramide may be an effective and tolerated drug in CIH, but more data is required to establish its place in the pharmacotherapy of this condition.

Investigation of the effect of metoclopramide on proliferation signal molecules in breast tissue.

Metoclopramide (MCP) is a drug that has been widely used in recent years due to its hyperprolactinaemia effect on mothers during breastfeeding. The aim of this study was to investigate the proliferative changes that MCP may cause in the maternal breast tissue. In this study, 18 Wistar albino young-adult breastfeeding mothers with their offspring were divided into three groups: control group, low-dose MCP-applied group and high-dose MCP-applied group. The experiment was carried out during the lactation period and at the end of 21 days. Prolactin, BrdU and Ki-67 breast tissue distributions were evaluated by immunohistochemistry, and tissue levels were evaluated biochemically by the ELISA method. According to ELISA and immunohistochemistry results in breast tissue, there was no significant difference between Ki-67 and BrdU results in all groups. Metoclopramide did not change the expression of proliferation molecules Ki-67 and BrdU in breast tissue. These results suggested that while metoclopramide increases breast proliferation, it does not have the risk of transforming the tissue into a tumour.

Efficacy of ketorolac in the treatment of acute migraine attack: A systematic review and meta-analysis.

OBJECTIVES: This review was designated to evaluate the efficacy of parenteral ketorolac in treating acute migraine headache. METHODS: We searched databases Cochrane Central Register of Controlled Trials (CENTRAL), Medline, and Google Scholar up to January 2021 and identified randomized controlled trials comparing ketorolac to any other medications in treating patients presenting with migraine headache. RESULTS: Thirteen trials were included in our review, comprising 944 participants. We derived seven comparisons: ketorolac versus phenothiazines, metoclopramide, sumatriptan, dexamethasone, sodium valproate, caffeine, and diclofenac. There were no significant differences in the reduction of pain intensity at 1 h under the comparisons between ketorolac and phenothiazines (standard mean difference [SMD] = 0.09, p = 0.74) or metoclopramide (SMD = 0.02, p = 0.95). We also found no difference in the outcome recurrence of headache (ketorolac vs. phenothiazines (risk ratio [RR] =0.98, p = 0.97)], ability to return to work or usual activity (ketorolac vs. metoclopramide [RR = 0.64, p = 0.13]), need for rescue medication (ketorolac vs. phenothiazines [RR = 1.72, p = 0.27], ketorolac vs. metoclopramide [RR 2.20, p = 0.18]), and frequency of adverse effects (ketorolac vs. metoclopramide [RR = 1.07, p = 0.82]). Limited trials suggested that ketorolac offered better pain relief at 1 h compared to sumatriptan and dexamethasone; had lesser frequency of adverse effects than phenothiazines; and was superior to sodium valproate in terms of reduction of pain intensity at 1 h, need for rescue medication, and sustained headache freedom within 24 h. CONCLUSIONS: Ketorolac may have similar efficacy to phenothiazines and metoclopramide in treating acute migraine headache. Ketorolac may also offer better pain control than sumatriptan, dexamethasone, and sodium valproate. However, given the lack of evidence due to inadequate number of trials available, future studies are warranted.

Randomized Clinical Trial of Metoclopramide as Prophylaxis of Gastroesophageal Reflux Disease in Preterm Infants.

BACKGROUND: Gastroesophageal reflux (GER) is more frequent in premature infants. Metoclopramide was introduced routinely in premature babies followed in ambulatory care by the Colombian Kangaroo Mother Care program (KMCP), based on a 2004 Cochrane review. AIM: Because of the recent controversy on the use of metoclopramide in children, this study was conducted to evaluate the effectiveness and safety of metoclopramide given as GER disease (GERD) prophylaxis. METHODS: A randomized clinical trial was conducted between April 2017 and January 2019 in 466 premature infants discharged home and followed at a KMCP. Double-blind allocation to metoclopramide versus placebo was performed, 0.2 mg/kg three times daily, administered 15 min before feeding, up to term. Exclusion criteria were oxygen dependency, any perinatal neurological problem or parent's participation refusal. The incidence of GERD symptoms and adverse events that could be associated with the use of metoclopramide were recorded by parents weekly (e.g., emesis, cyanosis or apnea, post-prandial crying episodes, extrapyramidal symptoms, tremor, and drowsiness). RESULTS: A total of 466 subjects were recruited, most of them late preterm. The groups' baseline characteristics were similar. Median duration of the intervention was approximately 3 weeks, at which time most patients were at term. In the longitudinal mixed effects analysis, we did not find clinically significant differences in GERD-related symptoms between groups, either in minor or severe side effects. CONCLUSION: Results show absence of effectiveness in the systematic use of metoclopramide as prophylaxis of GERD symptoms in premature infants. Additionally, no adverse effects attributable to the drug were found. ClinicalTrials.gov: NCT02907632; September 20, 2016. Retrospectively registered.

Metoclopramide-induced acute dystonic reactions: a case report.

BACKGROUND: Acute dystonic reactions caused by drugs are uncommon in daily practice, whether in outpatient or in emergency settings. Such types of unfavorable reaction may cause the treating physician's working diagnosis to be misled at a certain point. CASE PRESENTATION: A 25-year-old Hindu female from Dharan with no previous medical history was being treated for acid peptic disease. Her local physician prescribed oral tablet metoclopramide 10 mg three times a day for 7 days and tablet pantoprazole 40 mg once daily for 7 days. After 24 hours of ingestion of 10 mg of tablet metoclopramide, she was admitted to our Koirala Institute of Health Sciences emergency department with sudden history of facial twitching, slurred speech, and abnormal tongue protrusion. Metoclopramide-induced acute dystonic reaction was diagnosed. After resuscitation, her symptoms reduced quickly, and she was successfully discharged home the same day. CONCLUSIONS: Early diagnosis would be aided by the use of clinical background along with focus on drug history usage, preventing life-threatening pitfalls. To decrease the acute dystonic reaction associated with metoclopramide use, higher frequency of prescription patterns should be taken into account.