Abortive Headache Therapy With Intramuscular Dihydroergotamine

During a six month period, intramuscular dihydroergotamine mesylate (1 mg.) was given to 43 patients (75 headache episodes) who presented to the office after oral medications failed to abort their headaches. Headaches were successfully aborted in 71%, with most responses occurring between 30-minutes and 4-hours after injection. Side effects were common (61%) but not serious; sedation developed in 25%, nausea in 24%, transient worsening of headaches in 15%, body aches in 11%, diarrhea in 5%, and in 13%, headaches that were successfully aborted relapsed within 24 hours. Intramuscular dihydroergotamine, although under-used, is cost effective, practical, and well suited for busy medical offices. Its appropriate use can reduce the need for narcotic analgesics and emergency room visits.     

Prochlorperazine vs. promethazine for headache treatment in the emergency department: a randomized controlled trial

Headache is a very common medical complaint. Four to six percent of the population will have a debilitating headache in their lifetime; and 1-2% of all Emergency Department (ED) visits involve patients with headaches. Although promethazine is used frequently, it has never been studied as a single-agent treatment in undifferentiated headache. We hypothesized that promethazine would be superior to prochlorperazine in the treatment of headache. We conducted a prospective, double-blinded, randomized, controlled trial on patients presenting to our ED between May and August 2005 with a chief complaint of headache. Each subject was randomized to receive either intravenous promethazine 25 mg or prochlorperazine 10 mg, and graded the intensity of their headache on serial 100-mm visual analog scales (VAS). Patients with dystonic reactions or akathesia were treated with diphenhydramine. Adequate pain relief was defined as an absolute decrease in VAS score of 25 mm. After discharge from the ED, patients were queried regarding the recurrence of headache symptoms, the need for additional pain medications, and the occurrence of any side effects since discharge. Thirty-five patients were enrolled in each group. Both drugs were shown to be effective in treatment of headaches. Prochlorperazine provided a faster rate of pain resolution and less drowsiness when compared to promethazine. Both medications were individually effective as abortive therapy for headache. Prochlorperazine was superior to promethazine in the rate of headache reduction and rate of home drowsiness, with similar rates of akathesia, nausea resolution, patient satisfaction, and headache recurrence within 5 days of discharge.     

Abortive Migraine Therapy in the Office with Dexamethasone and Prochlorperazine

SYNOPSIS
Corticosteroids are commonly used in the abortive therapy of status migrainosus. However, this practice is based more on clinical experience than on published data. At my office, over a period of two years, 108 patients (156 migraine episodes) were treated with intravenous dexamethasone. Most of these patients had prolonged migraines that had resisted other forms of abortive therapy. The first 22 patients (32 migraine episodes) were given 10 mg of dexamethasone over 5 minutes, the next 39 patients (55 migraine episodes) were given 20 mg over 10 minutes, and the last 47 patients (69 migraine episodes) were given 3.5 mg of prochlorperazine over 5 minutes followed by 20 mg of dexamethasone over 10 minutes. Adverse effects were minor and patients with episodic migraines responded more favorably than those with intractable migraines. In the episodic migraine groups, response rates ranged from 80–89%, relapse rates from 29–35%, and remission rates from 57–83%. After the intravenous injections, repetitive oral abortive therapy was often required to treat relapses and secure remission. Adding 3.5 mg of pro-chlorperazine to 20 mg of intravenous dexamethasone significantly shortened the response time.     

Droperidol vs. Prochlorperazine for Benign Headaches in the Emergency Department

OBJECTIVE: To compare the efficacy of droperidol with that of prochlorperazine for the treatment of benign headaches in emergency department (ED) patients. METHODS: Prospective, randomized clinical trial in an urban ED. Patients were given either droperidol, 5 mg intramuscular (IM) or 2.5 mg intravenous (IV), or prochlorperazine, 10 mg IM or 10 mg IV. Measurements included side effects and the patient's pain perception as measured on a 100-mm visual analog scale (VAS) at baseline, 30, and 60 minutes after the medication was given. Data were analyzed using chi-square, two-tailed t-tests, and two-way analysis of variance (ANOVA) when appropriate. RESULTS: During an eight-month period, 168 patients were enrolled. Eighty-two (48.8%) of the patients received droperidol; 86 (51.2%) received prochlorperazine. In the droperidol group, 49 (59.6%) received IM administration and 33 (40.4%) IV. In the prochlorperazine group, 57 (66.3%) received IM administration and 29 (33.7%) IV. Sixty minutes after the medication, the mean decrease in the VAS scores was 81.4% for droperidol and 66.9% for prochlorperazine (p = 0.001). At 30 minutes, 60.9% of the patients receiving droperidol and 44.2% of the patients receiving prochlorperazine had obtained at least a 50% reduction in their VAS scores (p = 0.09). At 60 minutes, 90.2% of the patients receiving droperidol and 68.6% of the patients receiving prochlorperazine had at least a 50% reduction in their VAS scores (p = 0.017). No difference between IM dosing and IV dosing was detected. Side effects, including dystonia, akathisia, and decreased level of consciousness, were seen in 15.2% of the patients receiving droperidol and 9.61% of the patients receiving prochlorperazine. No significant or persisting morbidity was detected. CONCLUSIONS: Droperidol was more effective than prochlorperazine in relieving pain associated with benign headaches.     

Pharmacokinetics and safety of prochlorperazine in paediatric patients receiving cancer chemotherapy.

Nausea and vomiting are common clinical problems in patients receiving cancer chemotherapy. Metoclopramide is often used but frequently causes extrapyramidal reactions. As an alternative, prochlorperazine is prescribed but no data on its pharmacokinetics in paediatric patients are available to guide the choice of suitable dosages. The primary objective of this study was to evaluate the pharmacokinetics and safety of intravenous prochlorperazine in paediatric patients receiving cancer chemotherapy. Eleven patients (ages 1-9 years) who received high doses of cisplatin or cyclophosphamide were given three to four intermittent doses of 0.2 mg/kg prochlorperazine i.v. over a period of 6-9 h. Multiple blood samples were collected and prochlorperazine was quantified by a specific gas-liquid chromatographic method. The peak serum concentrations ranged from 402 to 5,608 ng/ml. The total clearance and elimination half-life ranged from 0.03 to 0.28 (mean: 0.12) litre/kg/h, and from 1.2 to 15.5 (mean: 5.6) h, respectively. No adverse effects were observed in our patients. Three patients had uncontrolled episodes of vomiting during prochlorperazine therapy. These data suggest: (i) that there was a substantial interpatient variability in prochlorperazine pharmacokinetics thus the dose requirement differed among patients; and (ii) that prochlorperazine appeared safe at the doses used but higher doses may be required to control nausea and vomiting in some paediatric patients receiving high-dose cisplatin or cyclophosphamide therapy.     

Repetitive intravenous prochlorperazine treatment of patients with refractory chronic daily headache

OBJECTIVES: To investigate the efficacy and long-term outcome of intravenous prochlorperazine for the treatment of refractory chronic daily headache. BACKGROUND: Unlike dihydroergotamine, the treatment results of intravenous neuroleptics as first-line agents for refractory chronic daily headache have rarely been reported. METHODS: We retrospectively analyzed the data of inpatients with refractory chronic daily headache who received intravenous repetitive prochlorperazine treatment from November 1996 to March 1999. A semistructured telephone follow-up interview was done in September 1999. RESULTS: A total of 135 patients (44 men, 91 women) were recruited, including 95 (70%) with analgesic overuse. After intravenous prochlorperazine treatment, 121 (90%) achieved a 50% or greater reduction of headache intensity, including 85 (63%) who became headache-free. The mean hospital stay was 6.2 +/- 2.7 days, and mean total prochlorperazine used was 98 +/- 48 mg. Acute extrapyramidal symptoms occurred in 21 patients (16%). One hundred twenty-four patients (92%) were successfully followed up, with a mean duration of 14.3 +/- 7.5 months. Compared with pretreatment status, 93 patients (75%) considered their headache intensity decreased, and 86 patients (69%) considered their headache frequency decreased, although 40 (32%) still had a daily headache. Of the 87 patients with analgesic overuse who could be followed, 61 (70%) no longer overused analgesics. Poor response to prochlorperazine treatment (relative risk, 1.8) and presence of major depression (relative risk, 1.8) were predictors of persistent chronic daily headache at follow-up. CONCLUSIONS: Prochlorperazine was effective and safe in the treatment of patients with refractory chronic daily headache with or without analgesic overuse. Compared with dihydroergotamine, prochlorperazine seemed less effective at achieving "freedom from headache" during hospitalization, but had a similar outcome at follow-up.     

Naratriptan in the prophylaxis of cluster headache

A 36-year-old man with cluster headache refractory to trials of standard prophylactic treatment and only partially responsive to parenteral sumatriptan and inhaled oxygen was admitted to an inpatient pain unit. The diagnosis of cluster headache was confirmed by direct observation of a typical attack. Despite efforts at prophylaxis, the patient continued to experience three to four severe headaches per day. Attempts to control his headaches with scheduled parenteral dihydroergotamine were successful, but headaches recurred when the medication was tapered, and continuous or intermittent use of parenteral dihydroergotamine was not felt to be a practical option for the patient. Naratriptan 2.5 mg twice daily completely abolished his headaches, which recurred when the medication was discontinued. No electrocardiographic or laboratory abnormalities were observed during treatment, and the patient reported no side effects.     

Comparison of Dihydroergotamine With Metoclopramide Versus Meperidine With Promethazine in the Treatment of Acute Migraine

Migraineurs often seek office-based treatment for acute headache. To compare the efficacy and side effect profile, we entered 27 migraineurs into a prospective, randomized, double-blind study where each patient received either 75 mg meperidine with 25 mg promethazine IM or .5 mg dihydroergotamine with 10 mg metoclopramide IV. After I hour, pain relief was similar in the two groups, but side effects were significantly greater in the meperidine with promethazine regimen group. The dihydroergotamine with metoclopramide regimen is effective, and has minimal side effects, making it an attractive method for office-based treatment of acute migraine.     

Management of Acute Intractable Headaches Using IV Therapy in an Office Setting

Twenty-seven consecutive patients with acute intractable headaches were treated in an office setting with an intravenous protocol of an antiemetic, hydrocortisone sodium succinate, and dihydroergotamine (DHE). All patients had significant pain relief within 45 minutes. Patients who were not pain-free post-treatment uniformly reported decreasing pain at the time of departure from the office. No patients required further treatment (including narcotic medication) for acute headache. All patients were followed for at least 24 hours. Adverse reactions were transient and mild. Akathisia was not uncommon and has probably been underestimated in previous studies.     

Treatment of Childhood Headache with Dihydroergotamine Mesylate

SYNOPSIS
This study was undertaken to determine whether pediatric patients with migraine without aura who have failed standard outpatient regimens including intravenous dihydroergotamine mesylate (DHE) in conjunction with oral metoclopramide would respond to an inpatient treatment protocol of intravenous DHE and oral metoclopramide. Thirty patients were evaluated in this study which was an open label, retrospective review of treatment. Independent of the duration of the refractory migraine, 80% of the patients responded to the protocol with only minimal side effect. The dose of DHE mesylate ranged from 0.1 to 0.5 mg. The dose of DHE is lower than is typically utilized in standard adult protocols. The patients received an average of five doses of DHE.     

Early and Transient Side Effects of Repetitive Intravenous Dihydroergotamine

Side effects associated with administration of repetitive intravenous dihydroergotamine (DHE) were prospectively studied in 72 patients with chronic daily headache who ware hospitalized in a dedicated inpatient headache treatment program. All patients received 11 consecutive doses of DHE, starting with 0.25 mg and increasing by 0.25 mg up to a maximum dose of 1.25 mg, depending on side effects and/or headache relief. The adverse events were recorded after each dose administered.
The great majority of patients (91.6%) reported at least one side effect. The most common were: nausea (72.2%), increase in previous headache (47.2%), lightheadedness (33.3%), "new" headache (27.8%), and leg cramps (23.6%). The overall number of side effect complaints did not increase proportionally with the strength of the dose of DHE administered. These complaints declined from the earlier to the later doses of DHE, except for leg cramps, which were more common with the later doses.
Side effects determined the strength of subsequent doses of DHE in only 18.1% of patients. Only four patients had to have a decrease in dosage and none required termination of DHE due to side effects.
Although repetitive intravenous DHE causes frequent side effects, they are usually mild and transient and decrease with subsequent doses, even at higher doses.     

Outpatient Home‐Based Continuous Intravenous Dihydroergotamine Therapy for Intractable Migraine

(Headache 2010;50:852‐860) Background.— Established consecutive‐day inpatient intravenous dihydroergotamine protocols administered by bolus intravenous injection or continuous infusion injection in the hospital have demonstrated efficacy and safety in modifying the course of daily intractable headache. We conducted a study to determine efficacy, tolerability, and feasibility to treat patients with daily intractable headache with continuous intravenous dihydroergotamine in an outpatient home‐based setting. Methods.— A total of 31 patients fulfilling ICHD‐II criteria for chronic daily headache, 25 with chronic migraine and 6 with medication overuse headache, were treated with outpatient home‐based continuous intravenous dihydroergotamine for 3 days. Patients were pretreated with 10 mg intravenous metoclopramide prior to the first day of infusion and administered 3 mg dihydroergotamine given continuously at a rate of 42 mL/hour on day 1 and 2, and administered 1.5 mg on day 3 at the rate of 21 mL/hour. The primary end point was a change in pain intensity, as measured by an 11‐point numeric pain intensity scale at the end of 3 days. The secondary end point was reduction in headache frequency at long‐term follow‐up. Results.— Patients reported an average of 63.4% reduction in the intensity of migraine pain by the end of the 3‐day infusion. Side effects were minimal and no serious adverse effects occurred. Approximately one‐third of patients became completely headache‐free after day 3, and 1 patient had no improvement. Long‐term follow‐up data indicated an average 86% reduction in headache frequency and almost every patient converted from chronic daily headache to episodic migraine except for 1 patient. Patients with medication overuse headache were no longer consuming the daily offending medication. Conclusions.— Efficacy and safety of our outpatient home‐based intravenous dihydroergotamine program compared favorably to that of established inpatient intravenous pulse injection and continuous infusion protocols for the treatment of intractable migraine. The use of outpatient continuous intravenous dihydroergotamine is an effective and well‐tolerated therapy for intractable migraine but without the added cost and inconvenience of hospitalization.     

Case reports: sudden worsening of cluster headache: A signal of aneurysmal thrombosis and enlargement

We report a 55-year-old man presenting with symptoms of cluster headache, including throbbing pain behind the left eye, tearing, and rhinorrhea. Magnetic resonance imaging and magnetic resonance angiography revealed no abnormalities. Two days of intravenous dihydroergotamine resolved his pain. His headaches were somewhat relieved with a treatment regimen of 100 mg of imipramine each night, 40 mg of propranolol twice a day, 250 mg of divalproex three times a day, and dihydroergotamine nasal spray for breakthrough headaches. Two months later, the severity of his pain increased dramatically. Repeat imaging revealed a large thrombosed left posterior communicating artery aneurysm. Following obliterative surgery, his headaches are infrequent and mild and resemble tension headaches. Dramatic changes in headache characteristics can be an indicator of aneurysmal enlargement and thrombosis. This case illustrates the importance of repeat imaging when a patient's headache significantly worsens.     

A Controlled Study of Dihydroergotamine in the Treatment of Acute Migraine Headache

SYNOPSIS
A prospective, double-blind, crossover study was conducted of the effectiveness of dihydroergotamine (DHE) vs. placebo in the treatment of acute migraine in the emergency department. Thirty-seven patients were enrolled. By 60 minutes after treatment, those receiving DHE first had significantly better relief of pain than those receiving it later. Side effects were fairly common but were minor and did not necessitate terminating treatment. Eleven per cent of patients had significant relief of pain with prochlorperazine pre-treatment alone. Only 13.5% of patients treated with this DHE regimen required narcotics at the end of the study for relief of pain, compared to 45% of migraine headache patients seen concurrently in the same emergency department who were not enrolled in the study. We conclude that treatment with intravenous prochlorperazine and DHE is a safe and effective treatment and a useful alternative to narcotics.     

Comparison of intravenous valproate versus intramuscular dihydroergotamine and metoclopramide for acute treatment of migraine headache

OBJECTIVE: To determine the effectiveness and tolerability of intravenous valproate for the acute treatment of migraine headache with or without aura (International Headache Society diagnostic criteria 1.1 and 1.2) compared with intramuscular metoclopramide 10 mg followed 10 minutes later by intramuscular dihydroergotamine 1 mg. BACKGROUND: Divalproex sodium is approved for prophylaxis of migraine headache. We studied the possible effectiveness of intravenous sodium valproate for the treatment of acute migraine headache. Valproate offers a treatment option for patients with migraine who recently have used a triptan or dihydroergotamine, theoretically avoiding the risk of drug interactions or cardiovascular complications. DESIGN/METHODS: In an open-label randomization, patients with an established diagnosis of migraine with or without aura were administered either intravenous valproate or intramuscular dihydroergotamine with metoclopramide to treat moderate-to-severe migraine headache of 24 to 96 hours' duration. Forty patients alternately received either 500 mg intravenous valproate or 10 mg metoclopramide intramuscularly followed by 1 mg dihydro- ergotamine. Patients rated severity of headache and the presence or absence of nausea, photophobia, or phonophobia at baseline, and at 1, 2, 4, and 24 hours. RESULTS: With intravenous valproate, 50% of patients reported headache improvement from moderate or severe to none or mild at 1 hour following treatment, 60% reported such improvement at 2 hours, 60% at 4 hours, and 60% at 24 hours. Corresponding improvement rates for dihydroergotamine were 45% at 1 hour, 50% at 2 hours, 60% at 4 hours, and 90% at 24 hours. Intravenous valproate and intramuscular dihydroergotamine provided similar relief from associated migrainous symptoms (nausea, photophobia, and phonophobia) during the first 4 hours following treatment. While none of the patients who received intravenous valproate experienced drug-related side effects during treatment, 15% of patients who took dihydroergotamine experienced one or more episodes of nausea and diarrhea during the first 4 hours of treatment. CONCLUSIONS: Intravenous valproate is similar in effectiveness to dihydroergotamine/metoclopramide as abortive therapy for prolonged moderate-to-severe acute migraine headache. Although the results were not statistically significant (P =.3635), intravenous valproate appears to offer a safe, effective, and well-tolerated treatment for patients with acute migraine. Relative to dihydroergotamine/metoclopramide, however, headache relief was not as likely to be sustained at 24 hours as with intravenous valproate.     

Abortive Migraine Therapy With Oral Naproxen Sodium Plus Metoclopramide Plus Ergotamine Tartrate With Caffeine

The oral tablet combination, (550 mgs. of naproxen sodium plus 10 mgs. of metoclopramide plus 1 mg. of ergotamine tartrate plus 100 mgs. of caffeine), was retrospectively studied in 63 patients who used it to abort migraine headaches. On the average, 84% of the headaches were totally aborted; minor side effects occurred in 40% of the patients, and 87% of the patients considered the combination superior to all prior treatments.     

Antiemetics in the ED: a randomized controlled trial comparing 3 common agents

We sought to compare the efficacy of 3 intravenous antiemetic medications in ED patients complaining of moderate to severe nausea. This randomized, placebo-controlled, double-blind trial compares 1.25 mg droperidol, 10 mg metoclopramide, 10 mg prochlorperazine, and saline placebo. Adult ED patients complaining of nausea were eligible. Nausea was measured on a 100-mm visual analog scale at 0 and 30 minutes after treatment. A convenience sample of 100 patients was enrolled; 97 had complete data available for analysis. Of these, 22 patients received droperidol, 25 received metoclopramide, 24 received prochlorperazine, and 26 received placebo. Droperidol (-54.5 mm) was significantly better than metoclopramide (-40.2 mm) or prochlorperazine (-40.5 mm) at reducing nausea at 30 minutes (P = .04). There were no significant differences in rescue medication or patient satisfaction; however, droperidol had significantly higher akathisia (71.4% vs 23.5%) at 24-hour follow-up. When administered intravenously to adult patients with moderate to severe nausea, droperidol was more effective than metoclopramide or prochlorperazine but caused more extrapyramidal symptoms. Metoclopramide and prochlorperazine were not more effective than saline placebo. All patients improved over time and possibly with intravenous hydration.     

Roller coaster migraine: an underreported injury?

A 28-year-old woman presented with severe headache, sleep problems, memory problems, and irritability 2 months after a violent roller coaster ride. She was diagnosed with posttraumatic migraine, and intravenous dihydroergotamine resolved her symptoms. Imaging studies, electroencephalogram, and visual and auditory evoked responses were normal. Imipramine, divalproex sodium, and propranolol were prescribed to prevent the headaches from recurring and dihydroergotamine nasal spray was prescribed for breakthrough headaches. We consider the many short but significant brain insults delivered during the roller coaster ride a critical factor in triggering this instance of posttraumatic migraine, which while unmanaged was a source of significant disability for the patient.     

Intravenous nizatidine kinetics and acid suppression

The effectiveness of intravenous nizatidine in suppressing gastric acid secretion was evaluated by different methods of inducing secretion in two single-blind studies. In study 1, seven subjects were given single, 20-min intravenous infusions of nizatidine (6.25, 25, 75, 150, or 250 mg) before modified sham feeding (MSF). Gastric acid suppression after nizatidine was contrasted with that after placebo and MSF. All doses of nizatidine reduced secretion; the 150- and 250-mg doses of nizatidine suppressed secretion for at least 2.5 hr. In study 2, eight subjects received one 5-min intravenous infusion of placebo, cimetidine (300 mg), or nizatidine (25, 50, 100, or 250 mg) weekly for 6 wk. Secretion was induced by infusing pentagastrin (2 micrograms/kg/hr) 45 min before the study drug was dosed and for 3.5 hr thereafter. Again, all doses of nizatidine reduced gastric acid, chiefly by decreasing volume. Nizatidine induced a clear dose-response effect; nizatidine (100 mg) and cimetidine (300 mg) had approximately equal suppressive effects. Nizatidine (100 mg) and cimetidine (300 mg) reduced acid output by 62% and 63% and reduced volume of secretion by 48% and 51% over the 3.5-hr period. Gastric acid suppression and plasma nizatidine concentrations were directly related. Nizatidine kinetics were linear and proportional to dose. The t1/2 was 1.3 hr (range 0.7 to 2.1 hr), the volume of distribution was 1.2 +/- 0.5 l/kg, and clearance was 0.6 +/- 0.2 l/kg/hr. Laboratory abnormalities and side effects were minor in both studies.     

Effects of low-dose naloxone on opioid therapy in pediatric patients: a retrospective case-control study

Objective To develop novel therapies that prevent opioid tolerance in critically ill children we examined the effects of low-dose naloxone infusions on patients' needs for analgesia or sedation. Design and setting Matched case-control study in a pediatric intensive care unit at a university children's hospital. Patients We compared 14 pediatric ICU patients receiving low-dose naloxone and opioid infusions with 12 matched controls receiving opioid infusions. Measurements and main results Opioid analgesia and sedative requirements were assessed as morphine- and midazolam-equivalent doses, respectively. No differences were observed between groups in opioid doses at baseline or during naloxone, but in the postnaloxone period opioid doses tended to be lower in the naloxone group. Compared to baseline the naloxone group required more opioids during naloxone but fewer opioids after naloxone. Total sedative doses were comparable at baseline in both groups, with no differences in the postnaloxone period. The naloxone group required less sedation after naloxone but sedation doses were unchanged in controls. The two groups did not differ in pain scores, sedation scores, or opioid side effects. Conclusions Naloxone did not reduce the need for opioid during the infusion period but tended to reduce opioid requirements in the postnaloxone period without additional need for sedation. Randomized clinical trials may examine the effects of low-dose naloxone on opioid tolerance and side effects in pediatric ICU patients requiring prolonged opioid analgesia. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. The authors gratefully acknowledge grant support from National Institute for Child Health and Human Development (NIH grants U10-HD50009 and R01-HD36484 to K.J.S.A.) and ZonMw 940-31-086, 940-39-004 (to D.T.) and the help of J.M. Tilford, Ph.D. for PRISM analyses.