Migraine References =================== 1. Randomized, placebo-controlled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache. 2. Abortive headache therapy in the office with intravenous dihydroergotamine plus prochlorperazine 3. Safety and efficacy of rectal prochlorperazine for the treatment of migraine in the emergency department [published erratum appears in Ann Emerg Med 1994 Oct;24(4):618] 4. Adverse neuropsychiatric effects of dopamine antagonist medications. Misdiagnosis in the medical setting. 5. The effects of two anti-vertigo drugs (betahistine and prochlorperazine) on driving skills. 6. Drug-induced dystonia in a patient with C4 quadriplegia. Case report. 7. Neuroleptic malignant syndrome associated with prochlorperazine. 8. Acute oculogyric crisis after administration of prochlorperazine. 9. The pharmacokinetics and effects of prochlorperazine in elderly female volunteers. 10. Abortive migraine therapy in the office with dexamethasone and prochlorperazine. 11. Intramuscular prochlorperazine versus metoclopramide as single-agent therapy for the treatment of acute migraine headache. 12. Modern pharmacotherapy of migraine. 13. Clinical pharmacology of prochlorperazine in healthy young males. 14. Isolated lingual/palatal dystonia. 15. Complications in the use of prochlorperazine. 16. Persistent extrapyramidal syndrome with dystonia and rigidity caused by combined metoclopramide and prochlorperazine therapy. 17. Extrapyramidal side effects of antiemetics presenting as psychiatric illness. 18. A retrospective study of risk factors of akathisia in terminally ill patients [see comments] 19. Akathisia associated with prochlorperazine as an antiemetic: a case report [letter] No Abstract Provided. 1.Randomized, placebo-controlled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache. Author: Coppola M , Yealy DM, Leibold RA Abbreviated Journal Title: Ann Emerg Med 1995 Nov, Journal Volume: 26, Page Numbers: 541 - 546 Abstract: STUDY OBJECTIVE: To determine the comparative efficacy of i.v. metoclopramide and prochlorperazine for the initial emergency department treatment of migraine headache. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Military community hospital ED with an annual census of 75,000. PARTICIPANTS: Seventy consenting adults from a convenience sample of patients presenting with migraine headache similar to that experienced in at least one prior episode. Exclusion criteria were pregnancy, fever, signs of meningismus, altered sensorium, drug or alcohol use, oxygen saturation less than 90%, recent trauma or seizure, "worst headache," abnormal blood pressure, recent (within 48 hours) use of metoclopramide or prochlorperazine, and allergy to metoclopramide or prochlorperazine. INTERVENTIONS: In a random manner, each subject received a 2-mL i.v. injection of identical-appearing fluid containing metoclopramide (10 mg), prochlorperazine (10 mg), or saline solution (placebo). No other analgesics or medications were administered during the initial study period; rescue agents were administered by the choice of the treating physician after all data were collected. MEASUREMENTS: Patients scored their nausea, pain, and sedation before receiving the 2-mL injections and at 30 minutes after injection. Ten-centimeter nonhatched visual analog scales were used for these measurements, with distance from the left end (zero) calculated for each use. Clinically important successful treatment was defined a priori as achievement of the following criteria: patient satisfaction and either a decrease of 50% or more in the 30-minute pain score (compared with the initial score) or an absolute pain score of 2.5 cm or less. Failure to achieve these criteria constituted treatment failure. Differences between groups were analyzed with the Kruskal-Wallis ANOVA and chi 2 tests. Data are reported as frequency percentages and median values, with a two-tailed P value of .05 or less considered significant. RESULTS: Nausea, pain, and sedation scores were similar in all three groups before therapy. Thirty minutes after treatment, pain scores differed among those treated with prochlorperazine (1.1 cm), with metoclopramide (3.9 cm), and with placebo (6.1 cm, P = .003). Clinical success occurred more commonly after treatment with prochlorperazine (82%) than after metoclopramide (46%) or placebo (29%, P = .03). However, metoclopramide and placebo scores did not differ (P = .14). Nausea tended to be improved after prochlorperazine, compared with metoclopramide or placebo, at 30 minutes (P = .64). Four patients (6%) returned to the ED for relapse of migraine headache within 24 hours (three in the placebo group and one in the metoclopramide group). CONCLUSION: i.v. prochlorperazine relieves the headache and tends to improve nausea better than metoclopramide in ED patients with acute migraine headache. ============================================================================ 2. Abortive headache therapy in the office with intravenous dihydroergotamine plus prochlorperazine [see comments] Author: Saadah HA Headache -- 1992 Mar;32(3):159 Abstract: Over two years, 92 patients were treated in the office for 146 severe headache episodes. Headaches were aborted using four different intravenous regimens containing 0.5 or 1 mg. of dihydroergotamine and 3.5, 5, or 10 mg. of prochlorperazine. The speed and rate of response were directly proportional to the prochlorperazine dose used. High prochlorperazine doses (10 mg.) aborted the most headaches (95%) in the shortest time, but caused more sedation and akathesia. Low doses (3.5 mg.) aborted less headaches (89%) and responses were delayed; but, on the other hand, sedation was minimal and akathesia mild and uncommon. Dihydroergotamine given alone caused intolerable side effects; but, when it was given with prochlorperazine, efficacy was enhanced and side effects were greatly reduced. Aborting headaches in the office can be reliably achieved with minimal side effects by administering an intravenous mixture containing 1 mg. of dihydroergotamine and 3.5 mg. of prochlorperazine. ============================================================================ 3. Safety and efficacy of rectal prochlorperazine for the treatment of migraine in the emergency department [published erratum appears in Ann Emerg Med 1994 Oct;24(4):618] Author: Jones EB, Gonzalez ER, Boggs JG, Grillo JA, Elswick RK Jr Abbreviated Journal Title: Ann Emerg Med,1994 Aug; 24( 237 - 241) Abstract: STUDY OBJECTIVE: To assess the safety and efficacy of rectal prochlorperazine in the treatment of acute migraines. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: Emergency department of an inner-city university hospital. PARTICIPANTS: ED patients with documented diagnosis of migraines. INTERVENTIONS: Vital signs and level of alertness were monitored immediately before drug administration and 120 minutes after dosing. Pain intensity and adverse events were monitored immediately before drug administration and at 30, 60, and 120 minutes after dosing. RESULTS: A positive outcome was defined as a pain score less than or equal to 5 on a 10-point scale or a 50% reduction in pain intensity from baseline at 120 minutes after dosing. All patients treated with prochlorperazine suppositories experienced a positive treatment outcome; only 50% of patients treated with placebo experienced a positive result at 120 minutes after dosing (P = .016). Pain intensity scores were significantly lower in the prochlorperazine group at 120 minutes (P = .018). There were no adverse reactions in either group, and there were no significant differences in vital signs or levels of alertness between groups. Patients who failed therapy were given rescue medication 120 minutes after dosing. CONCLUSION: Prochlorperazine administered as a 25-mg rectal suppository provides excellent pain relief within 2 hours in patients with acute migraines. ============================================================================ 4. Adverse neuropsychiatric effects of dopamine antagonist medications. Misdiagnosis in the medical setting. Author: Ferrando SJ, Eisendrath SJ Abbreviated Journal Title: Psychosomatics, 1991 Fall, Volume: 32, Page Numbers: 426 - 432 Abstract: Medications with central dopamine antagonist properties are in wide use in treating a variety of medical symptoms. Some of the most commonly used are metoclopramide (Reglan), prochlorperazine (Compazine), droperidol (Inapsine), and promethazine (Phenergan). The major adverse neuropsychiatric effects seen with these medications are acute dystonias, akathisia, parkinsonian symptoms, and neuroleptic malignant syndrome. These effects are often unrecognized or misdiagnosed by the primary physician as functional psychiatric disorders. The authors present four cases in which adverse neuropsychiatric effects from metoclopramide and prochlorperazine occurred with patients in the general hospital, and they discuss their initial misdiagnosis and subsequent identification and treatment by the consulting psychiatrist. The literature is reviewed on the adverse neuropsychiatric effects of metoclopramide and prochlorperazine, with attention to patient populations at risk. The authors believe that there is a key role in this area for the consulting psychiatrist, who can provide diagnostic clarity, advice on management, and ongoing staff education. ============================================================================ 5. The effects of two anti-vertigo drugs (betahistine and prochlorperazine) on driving skills. Author: Betts T, Harris D, Gadd E Abbreviated Journal Title: Br J Clin Pharmacol 1991 Oct, Journal Volume: 32, Page Numbers: 455 - 458 Abstract: 1. The effects of betahistine 72 mg three times daily, prochlorperazine 5 mg three times daily and placebo taken for 3 days before testing were compared on two actual driving tasks (weaving and gap estimation) and two psychomotor tasks (reaction time and kinetic visual acuity) in normal subjects in a double-blind prospectively randomised cross-over study. 2. The psychomotor effects of betahistine could not be distinguished from those of placebo. 3. Prochlorperazine impaired driving performance causing increased carelessness and slowing on the weaving test. 4. There was little subjective appreciation of impairment whilst taking prochlorperazine. ============================================================================ 6. Drug-induced dystonia in a patient with C4 quadriplegia. Case report. Author: Reecer MV Clinchot DM Tipton DB Abbreviated Journal Title: Am J Phys Med Rehabil 1993 Apr, Journal Volume: 72, Page Numbers: 97 - 98 Abstract: Prochlorperazine, a piperazine phenothiazine, is a commonly used anti-emetic that blocks dopamine receptors in the central nervous system. Prochlorperazine causes various extrapyramidal syndromes, with the incidence in the inpatient population estimated to be 0.5 to 0.8%. These side effects are typically manifested by motor dysfunction and easily observed on physical examination. We report the case of an 18-year-old male with C4 complete quadriplegia who developed an acute dystonic reaction isolated to the tongue during short-term treatment with prochlorperazine. This case demonstrates the importance of maintaining a high level of suspicion in the spinal cord population, considering that many key physical findings may be absent below the level of function. ============================================================================ 7. Neuroleptic malignant syndrome associated with prochlorperazine. Author: Manser TJ Warner JF Abbreviated Journal Title: South Med J 1990 Jan, Journal Volume: 83, Page Numbers: 73 - 74 Abstract: Neuroleptic malignant syndrome occurred in a patient with AIDS being treated with prochlorperazine. We believe this to be the first report of this association. Recognition and specific treatment were delayed in part because of overlap in signs and symptoms of the underlying infectious process. The true incidence of prochlorperazine-induced NMS is unknown, and this reaction may be underrecognized in patients who often have other significant medical illnesses. ============================================================================ 8. Acute oculogyric crisis after administration of prochlorperazine. Author: Schumock GT Martinez E Abbreviated Journal Title: South Med J 1991 Mar, Journal Volume: 84 Page Numbers: 407 - 408 Abstract: We report a case of acute oculogyric crisis due to prochlorperazine administration in a young black woman with a concomitant viral infection. Neuroleptic medications are the most common cause of drug- induced acute dystonic reactions such as oculogyric crisis. Prochlorperazine is an antiemetic agent with a phenothiazine-type chemical structure and is known to cause dystonic reactions. Drug-induced acute dystonic reactions are most common in young adults and in men. Viral infections may also predispose patients to these adverse reactions. Caution is warranted when this drug is used in patients who have other risk factors for an acute dystonic reaction. ============================================================================ 9. The pharmacokinetics and effects of prochlorperazine in elderly female volunteers. Isah AO Rawlins MD Bateman DN Abbreviated Journal Title: Age Ageing 1992 Jan, Journal Volume: 21, Page Numbers: 27 - 31 Abstract: The pharmacokinetics and effects of prochlorperazine (PCZ) have been studied in six healthy elderly female volunteers in a double-blind placebo-controlled study of 3.125 mg intravenous (IV) and 25 mg oral PCZ. The pharmacokinetics of IV PCZ in elderly subjects appear similar to those previously obtained in young subjects, with a terminal half-life of 7.5 +/- 1.8 h after intravenous dosing. Oral bioavailability was low (14.7 +/- 1.5%). The pharmacological actions of prochlorperazine in elderly people appear to include antidopaminergic (prolactin rise) and anticholinergic (reduced salivary flow) effects. At the dose of PCZ used in this study, no significant haemodynamic or psychomotor changes were observed though there was a trend to prolongation of the movement component of the reaction time. 10. Abortive migraine therapy in the office with dexamethasone and prochlorperazine. Author: Saadah HA Abbreviated Journal Title: Headache 1994 Jun, Journal Volume: 34m Page Numbers: 366 - 370 Abstract: 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 prochlorperazine to 20 mg of intravenous dexamethasone significantly shortened the response time. ============================================================================ 11. Intramuscular prochlorperazine versus metoclopramide as single-agent therapy for the treatment of acute migraine headache. Author: Jones J Pack S Chun E Abbreviated Journal Title: Am J Emerg Med 1996 May, Journal Volume: 14, Page Numbers: 262 - 264 Abstract: To compare the efficacy of intramuscular prochlorperazine and metoclopramide in the short-term treatment of migraine headache in the emergency department 86 eligible adult patients with moderate to severe migraine headache were evaluated prospectively at a university-affiliated community hospital. After randomization, each subject received a 2-mL intramuscular injection of sterile saline, prochlorperazine (10 mg), or metoclopramide (10 mg). No other analgesics were administered during the 60-minute study period; patient assessment of relief was followed using visual analog scales. Reduction in median headache scores was significantly better among those treated with prochlorperazine (67%) compared to metoclopramide (34%) or placebo (16%). Similarly, symptoms of nausea and vomiting were significantly relieved in the prochlorperazine group (chi 2 = 17.1, P prochlorperazine appears to provides more effective relief than metoclopramide, these results do not recommend either drug as single-agent therapy for acute migraine headache. ============================================================================ 12. Modern pharmacotherapy of migraine. Author: Raskin NH Abbreviated Journal Title: Neurol Clin, 1990 Nov, Journal Volume: 8, Page Numbers: 857 - 865 Abstract: Rectal ergotamine and naproxen are the major candidates for the ad hoc treatment of migraine attacks; for particularly dramatic episodes, intravenous DHE with prochlorperazine is the author's preference. For long-term stabilization, after simpler measures fail, valproate appears to be a major addition to migraine therapy. ============================================================================ 13. Clinical pharmacology of prochlorperazine in healthy young males. Author: Isah AO Rawlins MD Bateman DN Abbreviated Journal Title: Br J Clin Pharmacol, 1991 Dec, Journal Volume: 32, Page Numbers: 677 - 684 Abstract: 1. The pharmacokinetics and pharmacodynamics of prochlorperazine (PCZ) have been studied in healthy young males following single 12.5 mg i.v. and 50 mg oral doses, and during repeated doses (25 mg twice daily) for 14 days. 2. Oral bioavailability was low and an N-desmethyl metabolite was detected. Plasma clearance was high (0.98 1 kg-1 h) and the volume of distribution was large (12.9 1 kg-1) after i.v. dosing. 3. The terminal elimination half-life of PCZ was 9 +/- 1 h and 8 +/- 2 h after i.v. and single oral dosing, respectively. The urinary recoveries of drug and metabolite were low. 4. Accumulation of PCZ and its metabolite occurred following repeated dosing. The half-life at the end of 14 days therapy was 18 +/- 4 h. 5. Postural tachycardia, decreased salivary flow, impaired psychomotor function and a diminished level of arousal were observed after intravenous PCZ. Similar effects, but of lower magnitude were observed after single oral doses. During chronic dosing postural tachycardia and antihistaminic effects were observed, the latter not being observed after single doses. 6. After single intravenous dosing the maximal drug effects occurred 2-4 h after peak plasma drug concentrations for all measures except for plasma prolactin and self- scored restlessness 7. An antagonist action at dopamine (D2), muscarinic-cholinergic and alpha- adrenoceptors is postulated after single doses, with antihistaminic effects during chronic dosing, possibly indicating the presence of an active metabolite. ============================================================================ 14. Isolated lingual/palatal dystonia. Author: Robertson-Hoffman DE Mark MH Sage JI Abbreviated Journal Title: Mov Disord, 1991, Journal Volume: 6, Page Numbers: 177 through 179 Abstract: We report a 45-year-old woman with a 3-year history of continuous dystonic movements of tongue and palate with intermittent episodes of noticeable worsening lasting 6 to 8 h. The movements began immediately after a viral illness. The only contributory history is that the patient received high doses of prochlorperazine 22 years earlier for hyperemesis gravidarum. The patient appears to have an unusual focal lower cranial dystonia. Proposed etiologies may be idiopathic or related to prior use of a phenothiazine with a viral trigger. ============================================================================ 15. Complications in the use of prochlorperazine. Author: Luetzow TJ Abbreviated Journal Title: Wis Med J, 1991 Feb, Journal Volume: 90, Page Numbers: 64 - 65 Abstract: This case presentation is of a patient who had the clinical appearance of epiglottitis, but actually had an oro-pharyngeal dystonic reaction to prochlorperazine. The intent of the discussion is to alert physicians that the appearance of epiglottis can occur from causes other than infection and that a surgical airway should not be the first thought when such a case arises. ============================================================================ 16. Persistent extrapyramidal syndrome with dystonia and rigidity caused by combined metoclopramide and prochlorperazine therapy. Author: Factor SA Matthews MK Abbreviated Journal Title: South Med J 1991 May, Journal Volume: 84, Page Numbers: 626 - 628 Abstract: We have reported the case of a 58-year-old woman with cerebral palsy who experienced a persistent, generalized syndrome of dystonia and rigidity (tardive dystonia-parkinsonism) while being treated for vomiting with metoclopramide in combination with prochlorperazine. This syndrome was more severe than is typically seen in drug-induced extrapyramidal syndromes and may have contributed to her death. The extreme severity of this disorder was probably related to the use of a combination of dopamine antagonists in a patient who had premorbid cerebral dysfunction. Although dopamine antagonists should always be used with caution in individuals with cerebral dysfunction, this particular combination of antiemetics should probably be avoided in such patients. ============================================================================ 17. Extrapyramidal side effects of antiemetics presenting as psychiatric illness. Author: Rodgers C Abbreviated Journal Title: Gen Hosp Psychiatry 1992 May, Journal Volume: 14, Page Numbers: 192 - 195 Abstract: Although extrapyramidal side effects of two commonly used antiemetics, metoclopramide and prochlorperazine, are well known, it may be difficult for even the experienced practitioner to distinguish some of these extrapyramidal reactions from such psychiatric symptoms as anxiety, depression, or catatonia. Certain patient groups have increased susceptibility to these extrapyramidal reactions, including patients under 30, those with AIDS, those with renal disease, oncology patients, and possibly women. Physicians should maintain a high index of suspicion for depression, anxiety, or catatonia if their patients are taking antiemetics. These symptoms may be extrapyramidal side effects of the antiemetic rather than indications of a primary mental disorder. ============================================================================ 18. A retrospective study of risk factors of akathisia in terminally ill patients [see comments] Author: Gattera JA Charles BG Williams GM Cavenagh JD Smithurst BA Luchjenbroers J Abbreviated Journal Title: J Pain Symptom Manage, 1994 Oct, Journal Volume: 9, Page Numbers: 454 - 461 Abstract: Akathisia is a distressing disorder that manifests as a state of restlessness and motor agitation. We aim to highlight the problem of akathisia to the palliative care physician by identifying and quantifying risk factors in the terminally ill. A retrospective case-control study was utilized to investigate risk factors for akathisia. Medical records of cases (N = 100) and controls (N = 365) archived in a computerized database were downloaded and risk factors determined using conditional logistic regression analyses. Exposure to pharmacologically similar drugs, such as haloperidol [odds ratio (OR), 18.4; 95% confidence interval (CI), 8.2- 41.4], prochlorperazine (OR, 8.1; 95% CI, 3.0-21.8), and promethazine (OR, 3.3; 95% CI, 1.3-8.0), conferred an increased risk. Other significant variables were exposure to morphine (OR, 5.3; 95% CI, 1.9-14.2), sodium valproate (OR, 2.5; 95% CI, 1.0-6.4), and sodium bicarbonate/tartrate (Ural) (OR, 4.2; 95% CI, 1.2-15.3). Highlighting factors that predispose patients to akathisia emphasizes that this syndrome should not be forgotten when treating the terminally ill. It is recommended that those drugs identified should be judicially used and carefully monitored. ============================================================================ 19. Akathisia associated with prochlorperazine as an antiemetic: a case report [letter] No Abstract Provided. Author: Dukoff R Horak ID Hassan R Rosenstein DL Abbreviated Journal Title: Ann Oncol 1996 Jan, Journal Volume: 7, Page Numbers: 103 - 103