Prochlorperazine-induced neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is a rare yet severe condition typically associated with antipsychotic medications. Here, we present a case of NMS induced by prochlorperazine in a 76-year-old male with multiple comorbidities, aiming to delineate its clinical manifestation, diagnostic complexities, and treatment approaches. Our methodology involved a thorough documentation of the patient's medical history, initial symptoms, physical examination findings, laboratory results, diagnostic processes, and subsequent therapeutic interventions. The patient exhibited classic NMS symptoms, including fever, altered mental status, autonomic dysregulation, and generalized rigidity, consistent with diagnostic criteria. Notably, laboratory investigations failed to reveal the typical abnormalities often seen in NMS cases, highlighting the diverse presentation of this syndrome. Management strategies primarily focused on benzodiazepines and amantadine, leading to a gradual improvement in symptoms and eventual resolution of NMS. This underscores the critical role of early recognition and appropriate pharmacotherapy in managing prochlorperazine-induced NMS, even at standard dosage levels. The absence of characteristic laboratory findings in NMS poses challenges in diagnosis, necessitating a comprehensive clinical assessment for accurate identification. Moreover, this case emphasizes the need for further research to better understand the pathophysiology of prochlorperazine-induced NMS and optimize treatment protocols. In conclusion, our case report sheds light on the complexities surrounding NMS induced by prochlorperazine, emphasizing the importance of vigilant monitoring and tailored therapeutic strategies in mitigating its potentially life-threatening consequences.

A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs.

Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.

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.

A randomized study of IV prochlorperazine plus diphenhydramine versus IV hydromorphone for migraine-associated symptoms: A post hoc analysis.

OBJECTIVE: We conducted a randomized trial among emergency department patients with migraine to determine the relative impact on migraine-associated symptoms of hydromorphone, an opioid, versus prochlorperazine, an antidopaminergic antiemetic. METHODS: This was a post hoc analysis of data from a double-blind study registered at http://clinicaltrials.gov (NCT02389829). Patients who met International Classification of Headache Disorders, 3rd edition criteria for migraine without aura or for probable migraine without aura were eligible for participation. Participants received either hydromorphone 1 mg IV or prochlorperazine 10 mg IV plus diphenhydramine 25 mg IV and could receive a second dose of the same medication 1 h later if needed. The outcomes were sustained relief of nausea, photophobia, and phonophobia. RESULTS: A total of 127 patients were enrolled, of whom 63 received prochlorperazine and 64 received hydromorphone. Of 49 patients in the prochlorperazine arm who reported nausea at baseline, 34 (69.4%) reported complete resolution without relapse versus 15/49 (30.6%) in the hydromorphone arm (absolute risk reduction [ARR] = 38.8%, 95% CI: 20.5%-57.0%, p < 0.001). Of 55 patients in the prochlorperazine arm who reported photophobia at baseline, 23 (41.8%) reported complete resolution without relapse versus 13/62 (20.9%) patients treated with hydromorphone (ARR = 20.8%, 95% CI: 4.3%-37.3%, p = 0.014). Of 56 patients in the prochlorperazine arm who reported phonophobia at baseline, 25 (44.6%) reported complete resolution without relapse versus 16/59 (27.1%) in the hydromorphone arm (ARR = 17.5%, 95% CI: 0.3%-34.8%, p = 0.049). For adverse events, three patients in the prochlorperazine arm reported anxiety or restlessness, and nine patients in the hydromorphone arm reported dizziness or weakness. CONCLUSIONS: Prochlorperazine plus diphenhydramine is more efficacious than hydromorphone for the treatment of migraine-associated symptoms.

MAGraine: Magnesium compared to conventional therapy for treatment of migraines.

Due to the healthcare burden associated with migraines, prompt and effective treatment is vital to improve patient outcomes and ED workflow. This was a prospective, randomized, double-blind trial. Adults who presented to the ED with a diagnosis of migraine from August of 2019 to March of 2020 were included. Pregnant patients, or with renal impairment were excluded. Patients were randomized to receive intravenous magnesium, prochlorperazine, or metoclopramide. The primary outcome was change in pain from baseline on a numeric rating scale (NRS) evaluated at 30 min after initiation of infusion of study drug. Secondary outcomes included NRS at 60 and 120 min, ED length of stay, necessity for rescue analgesia, and adverse effects. A total of 157 patients were analyzed in this study. Sixty-one patients received magnesium, 52 received prochlorperazine, and 44 received metoclopramide. Most patients were white females, and the median age was 36 years. Hypertension and migraines were the most common comorbidities, with a third of the patients reporting an aura. There was a median decrease in NRS at 30 min of three points across all three treatment arms. The median decrease in NRS (IQR) at 60 min was -4 (2-6) in the magnesium group, -3 (2-5) in the metoclopramide group, and -4.5 (2-7) in the prochlorperazine group (p = 0.27). There were no statistically significant differences in ED length of stay, rescue analgesia, or adverse effects. Reported adverse effects were dizziness, anxiety, and akathisia. No significant difference was observed in NRS at 30 min between magnesium, metoclopramide and prochlorperazine.

An extrapyramidal reaction presenting as an acute temporomandibular episode: a case report.

This case report describes an adverse reaction (phenothiazine reaction) to prochlorperazine (Compazine), a commonly prescribed drug. The patient had been referred to a dental clinic for an oral evaluation because of muscle spasms in the oral musculature. He had severe muscle spasms, a reduced range of motion, difficulty registering a repeatable maximum intercuspation, facial grimacing, and difficulty speaking because of the spasms. The dental examination revealed no history of trauma to the musculature or the temporomandibular joints and no previous history of seizures. The patient was a young, healthy man who had recently been hospitalized for an upper respiratory infection and sinusitis. The drug regimen used to treat the sinusitis and respiratory infection caused some nausea and vomiting, and the patient received a prescription for prochlorperazine to control the symptoms. When questioned in the dental clinic about his medical and drug use history, he reported taking only amoxicillin for the infections. His symptoms worsened, necessitating a referral to a co-located emergency department. When he was asked specifically if he was taking Compazine, the patient reported that he had taken it earlier in the day. A tentative diagnosis of a phenothiazine reaction was made, and 50 mg of diphenhydramine was administered intramuscularly. The patient showed a marked alleviation of symptoms. Although the patient's reaction to the prochlorperazine is common, many dental care providers may never treat a patient with such symptoms. The phenothiazines are a common class of drugs, and some, such as prochlorperazine, are often prescribed by dentists. This case highlights the importance of taking an accurate history and being aware of possible adverse effects of medications.

The Real-World Safety and Effectiveness of Prochlorperazine in Indian Patients with Dizziness.

BACKGROUND: Considering the prevailing concerns about extrapyramidal symptoms (EPS) associated with oral prochlorperazine, this study was conducted to assess the safety of oral prochlorperazine (in recommended dose/duration) in the management of acute dizziness. Effectiveness was also assessed in the Indian real-world setting. METHODS: A prospective, multicentric, single-arm observational study was conducted across 20 centers in India. Data from 500 patients were analyzed. Patients presenting with a complaint of dizziness, receiving prochlorperazine (Stemetil® MD-5 mg, t.i.d.) as per the routine clinical practice were enrolled. Safety and effectiveness at Week-1, compared to baseline, were assessed. RESULTS: The mean (SD) age of the population was 43.3 (11.93) years with a marginally higher proportion of women (women: 52.2% Vs men 47.8%). The mean (SD) dose of prochlorperazine was 14.9 (0.24) mg/day. Only three patients (0.006%) reported adverse drug reactions (headache, asthenia, somnolence) during the conduct of the study, which were mild in severity and were completely resolved. Further, a significant reduction in the number of episodes of dizziness was noted at the end of Week-1(p<.0001). Moreover, improvement in the number of episodes from baseline to Week-1 was significant for nausea, vomiting, lightheadedness, and headache. CONCLUSION: Prochlorperazine was well-tolerated in the management of acute dizziness when administered at a mean dose of 14.9 mg/day, and mean duration of 7.2 days. Additionally, prochlorperazine was effective in providing significant symptomatic relief from dizziness and associated vomiting and nausea.

The Efficacy and Safety of Prochlorperazine in Patients With Acute Migraine: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this review was to evaluate the efficacy and safety of prochlorperazine (PCP) in patients with acute migraine headache in the emergency department (ED). METHODS: Electronic databases (Medline, Scopus, Web of Science, and Cochrane) were searched for randomized clinical trials that investigated the effect of PCP on headache relief. The outcomes were the number of patients without headache or with reduced headache severity, the number of adverse events, and the need for rescue analgesia. RESULTS: From 450 citations, 11 studies (n = 771) with 15 comparison arms met the inclusion criteria. Overall, PCP was more effective than placebo (OR = 7.23; 95% CI = 3.82-3.68), metoclopramide (OR = 2.89; 95% CI = 1.42-5.86), and other active comparators (OR = 3.70; 95% CI = 2.41-5.67) for headache relief. The odds ratio of experiencing adverse events with PCP compared with placebo was 5.79 (95% CI = 2.43-13.79). When PCP compared with other active comparators, no statistical difference was found regarding the overall number of adverse events (OR = 1.88; 95% CI = 0.99-3.59). However, PCP significantly increased the odds of akathisia/dystonia (OR = 2.55; 95% CI = 1.03-6.31). The request for rescue analgesia was significantly lower in the PCP group compared with other groups (16% vs 84%; OR = 0.16; 95% CI = 0.09-27). CONCLUSIONS: For adult patients with acute migraine, PCP could effectively abort the acute attack and reduce the request for rescue analgesia in the ED. However, compared with placebo, PCP could increase the risk of adverse events.

Efficacy of Prophylactic Treatment for Oxycodone-Induced Nausea and Vomiting Among Patients with Cancer Pain (POINT): A Randomized, Placebo-Controlled, Double-Blind Trial.

BACKGROUND: Although opioid-induced nausea and vomiting (OINV) often result in analgesic undertreatment in patients with cancer, no randomized controlled trials have evaluated the efficacy of prophylactic antiemetics for preventing OINV. We conducted this randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of prophylactic treatment with prochlorperazine for preventing OINV. MATERIALS AND METHODS: Cancer patients who started to receive oral oxycodone were randomly assigned in a 1:1 ratio to receive either prochlorperazine 5 mg or placebo prophylactically, given three times daily for 5 days. The primary endpoint was the proportion of patients who had a complete response (CR) during the 120 hours of oxycodone treatment. CR was defined as no emetic episode and no use of rescue medication for nausea and vomiting during 5 days. Key secondary endpoints were the proportion of patients with emetic episodes, proportion of patients with moderate or severe nausea, quality of life, and proportion of treatment withdrawal. RESULTS: From November 2013 through February 2016, a total of 120 patients were assigned to receive prochlorperazine (n = 60) or placebo (n = 60). There was no significant difference in CR rates (69.5% vs. 63.3%; p = .47) or any secondary endpoint between the groups. Patients who received prochlorperazine were more likely to experience severe somnolence (p = .048). CONCLUSION: Routine use of prochlorperazine as a prophylactic antiemetic at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations. IMPLICATIONS FOR PRACTICE: Prophylactic prochlorperazine seems to be ineffective in preventing opioid-induced nausea and vomiting (OINV) and may cause adverse events such as somnolence. Routine use of prophylactic prochlorperazine at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations.

Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.

BACKGROUND: Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use. OBJECTIVES: To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer. SEARCH METHODS: We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy. DATA COLLECTION AND ANALYSIS: At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results. AUTHORS' CONCLUSIONS: Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.

[A study on the antiemetic effect and extrapyramidal symptoms of prochlorperazine versus perospirone for the control of nausea and vomiting due to opioid introduction].

Prochlorperazine is often used to prevent opioid-induced nausea; however, this drug causes extrapyramidal symptoms. It is important to determine the incidence of such symptoms and identify coping mechanisms because these symptoms induce intense and possibly life-threatening patient suffering. The purpose of this study was to determine the incidences of nausea and extrapyramidal symptoms associated with the use of prochlorperazine and perospirone as preventive antiemetics when initiating opioid treatment(a sustained-release tablet of oxycodone at a dose of 10 mg/day)and to compare the benefits of the 2 drugs. A total of 100 cancer patients who received medical care from a physician in the palliative care department of our center between May 2007 and September 2008 were consecutively enrolled for a retrospective review of the medical records. Of the patients, 50 had received prochlorperazine treatment(10 or 15 mg/day, orally)and 50 had received perospirone treatment(4 or 8 mg/day, orally)concomitantly with oxycodone treatment(10 mg/day)on an in-patient or outpatient basis. The incidence of nausea and vomiting within 1 week after starting treatment with opioids and the extrapyramidal symptoms during treatment were evaluated. The results showed that the incidence of nausea and vomiting was 8. 0% for the prochlorperazine group and 4. 0% for the perospirone group, and this difference was not statistically significant; however, the incidence of extrapyramidal symptoms was significantly higher for the prochlorperazine group(14%)than for the perospirone group(0%). Furthermore, the extrapyramidal symptom observed in the prochlorperazine group was akathisia, which occurred within a week. The results of this study suggest that careful attention should be paid so as not to overlook akathisia when using prochlorperazine as an antiemetic in cancer patients and that atypical antipsychotics, such as perospirone, could be used as alternatives.

Prochlorperazine in children with migraine: a look at its effectiveness and rate of akathisia.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of prochlorperazine and the rate of akathisia in children with severe migraine. METHODS: The study is a prospective cohort of a convenient sample of patients younger than 18 years old diagnosed with migraine and treated with intravenous prochlorperazine in adjunction with diphenhydramine in the emergency department. The evaluation of pain and akathisia was performed before the treatment and was repeated 60 minutes later and before discharge. A telephone follow-up was completed to assess relapse in pain and presence of akathisia. The effectiveness of prochlorperazine was determined using different outcomes: 50% reduction of pain, pain-free patients, treatment failure, and relapse of pain. RESULTS: Of the 79 patients included in the study for 25 months, 64 (81%) either met the International Headache Society criteria or had a diagnosis of migraine confirmed by a neurologist at follow-up. Among these patients, 47 (100%) of 47 had a 50% reduction of pain, and 24 (50%) of 48 were pain free at discharge. Only 14 (22%) of 64 patients had a treatment failure. However, 43 (68%) of 63 patients had a relapse of their headache within the first week after discharge. Overall, among the 79 patients, 4 (5%) had a definitive diagnosis of akathisia, but 27 (34%) other patients presented symptoms suggesting a possible diagnosis of akathisia. CONCLUSION: Prochlorperazine seems very effective to decrease pain on a short-term basis in children. However, more than two thirds of the patients, overall, had a relapse of their migraine at home in the first week. Despite the use of diphenhydramine, akathisia remains a concern.

Neuroleptic malignant syndrome associated with the use of prochlorperazine in a patient with a recent history of antipsychotic-induced neuroleptic malignant syndrome.

OBJECTIVE: To describe a case of neuroleptic malignant syndrome (NMS) associated with the use of prochlorperazine in a patient recently hospitalized for NMS secondary to olanzapine. CASE SUMMARY: A 28-year-old African American male with a history of schizophrenia was hospitalized 22 days prior to the current admission for an episode of olanzapine-induced NMS. The patient was discharged from our hospital to an outside psychiatric facility. At this facility, the patient developed nausea and was given 2 doses (unknown amount and route) of prochlorperazine. Over the next 24 hours, the patient exhibited signs and symptoms of NMS including fever, agitation, and muscle rigidity. He was transported to the emergency department and became increasingly agitated. Upon admission, the patient was hyperthermic (rectal temperature 39 °C) and tachycardic (heart rate 138 beats/min), with an elevated white blood cell count of 13.5 × 10(3)/µL, creatine kinase 431 units/L, serum sodium 150 mEq/L, blood urea nitrogen 25 mg/dL, and creatinine 1.1 mg/dL. A diagnosis of NMS was speculated and infectious causes were excluded. The patient was treated with aggressive fluid resuscitation and rapid cooling measures, as well as bromocriptine and lorazepam. Cooling measures were used for 48 hours, during which time the creatine kinase, white blood cell count, sodium, blood urea nitrogen, and creatinine gradually normalized. The patient was discharged to a psychiatry facility with a treatment regimen of oxcarbazepine 600 mg twice daily, lorazepam 2 mg 3 times daily, and clozapine 25 mg at bedtime, which was titrated over 2 months to 200 mg twice daily. There have been no further occurrences of NMS. DISCUSSION: The patient had all of the major characteristics of NMS with no other likely causative factors that may have contributed to his illness. Use of the Naranjo probability scale suggested that NMS was probably related to prochlorperazine. This case highlights the potential increased risk with the use of prochlorperazine in a patient with a history of olanzapine-induced NMS. CONCLUSIONS: NMS should be considered as a rare complication of therapy with antipsychotics and agents that alter dopamine activity, especially in patients with a history of the syndrome. Careful consideration should be given regarding the risks and benefits of using non-antipsychotic dopamine antagonists in patients with a history of antipsychotic-induced NMS.

A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department.

STUDY OBJECTIVE: Intravenous (IV) prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine patients presenting to the emergency department (ED). METHODS: In this randomized, double-blind, placebo-controlled trial, after providing written informed consent, patients presenting to the ED with a chief complaint of migraine received a 500-mL bolus of IV saline solution and either 10 mg prochlorperazine with 12.5 mg diphenhydramine IV plus saline solution placebo subcutaneously or saline solution placebo IV plus 6 mg sumatriptan subcutaneously. Pain intensity was assessed with 100-mm visual analog scales (visual analog scale at baseline and every 20 minutes for 80 minutes). The primary outcome was change in pain intensity from baseline to 80 minutes or time of ED discharge if subjects remained in the ED for fewer than 80 minutes after treatment. Sedation and nausea were assessed every 20 minutes with visual analog scale scales, and subjects were contacted within 72 hours to assess headache recurrence. RESULTS: Sixty-eight subjects entered the trial, with complete data for 66 subjects. Baseline pain scores were similar for the prochlorperazine/diphenhydramine and sumatriptan groups (76 versus 71 mm). Mean reductions in pain intensity at 80 minutes or time of ED discharge were 73 mm for the prochlorperazine/diphenhydramine group and 50 mm for those receiving sumatriptan (mean difference 23 mm; 95% confidence interval 11 to 36 mm). Sedation, nausea, and headache recurrence rates were similar. CONCLUSION: IV prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine.

Increased risk of hip fracture in the elderly associated with prochlorperazine: is a prescribing cascade contributing?

PURPOSE: To examine the prescribing of prochlorperazine secondary to the prescribing of a medicine which could lead to symptoms for which prochlorperazine is indicated and commonly used. Given the range of potential hypotensive, sedative, dystonic and other extra-pyramidal side effects associated with prochlorperazine, its association with hip fracture was also examined. METHODS: Prescription/event sequence symmetry analyses were undertaken from 1st January 2003 to 31st December 2006, using administrative claims data from the Department of Veterans' Affairs, Australia. This method assesses asymmetry in the distribution of an incident event (either prescription of another medicine or hospitalization) before and after the initiation of prochlorperazine. Crude and adjusted sequence ratios (ASR) with 95% confidence intervals (CI) were calculated. RESULTS: A total of 34 235 persons with incident use of prochlorperazine were identified during the study period. Statistically significant positive associations were found for a number of commonly used medicines, including cardiovascular medicines, NSAIDs, opioids and sedatives and the subsequent initiation of prochlorperazine that ranged from 1.07 (95%CI 1.01-1.14) for diuretics to 1.50 (95%CI 1.40-1.61) for statins. Prescription event analysis showed a 49% (95%CI 1.19-1.86) increased risk of hospitalisation for hip fracture following dispensing of prochlorperazine. CONCLUSIONS: Prescribers should consider the possible contributing role of newly initiated medicines with the potential to cause of dizziness, and where possible address this through dose reduction or cessation of the medicine, rather than prescribing prochlorperazine.

Antiemetic therapy for nausea and vomiting in the emergency department.

BACKGROUND: Antiemetic agents are among the most frequently prescribed medications in the emergency department (ED). Nevertheless, there are no widely accepted evidence-based guidelines to optimize the use of these medications for nausea or vomiting in this setting. OBJECTIVE: The objective of this article is to briefly review the evidence supporting the use of antiemetic agents for the treatment of nausea or vomiting for adults in the ED, and to provide recommendations to help guide therapy. DISCUSSION: The antiemetic agents studied include droperidol, promethazine, prochlorperazine, metoclopramide, and ondansetron. Droperidol was commonly used in the past, and is more effective than prochlorperazine or metoclopramide, but due to the US Food and Drug Administration black box warning regarding the potential for QT prolongation with this drug, its use is limited to refractory cases. Promethazine is more sedating than other comparative agents, and also has the potential for vascular damage upon intravenous administration. It may be a suitable option when sedation is desirable. Patients given prochlorperazine or metoclopramide must be monitored for akathisia that can develop at any time over 48 h post administration. Decreasing the infusion rate can reduce the incidence of this adverse effect, and the effect can be treated with intravenous diphenhydramine. Ondansetron is as effective as promethazine, and is not associated with sedation or akathisia. CONCLUSION: Based on the safety and efficacy of ondansetron, it may be used as a first-line agent for relief of nausea or vomiting for most patient populations in the ED.

[Antiemetic-induced extrapyramidal symptoms seen by our palliative care team].

BACKGROUND: Antiemetic drugs, which are usually prescribed with opioids, occasionally induce extrapyramidal symptoms(EPS). METHODS: In 109 patients treated with our palliative care team, we retrospectively investigated the appearance of antiemetic-induced EPS; its incidence, latent period, onset age, symptoms, causing agents and clinical outcomes. RESULTS: EPS were observed in 6 of 109 patients. Six EPS patients, 2 men and 4 women, were between the age of 53 and 66 years. Prochlorperazine was used in all EPS patients. Two EPS were induced with unnecessary antiemetic drugs. Onset of EPS was from 11 to 162 days after beginning of antiemetic drugs. There were 5 patients with slow movement or speech, 3 patients with expressionless face, 2 patients with akathisia, and one patient with dysphagia. Five EPS patients were improved by using biperiden and one patient was by changing prochlorperazine to perospirone. CONCLUSIONS: EPS were found in 6 of 109 patients during palliative care. We concluded that it was important not to forget the appearance of antiemetic-induced EPS when prescribing antiemetic drugs in palliative

Acute Dystonic Reactions in Children Treated for Headache With Prochlorperazine or Metoclopramide.

BACKGROUND: The incidences of dystonic reactions to metoclopramide and prochlorperazine have not been well characterized in children. METHODS: Medical record data were reviewed for patients at a tertiary care pediatric hospital who received metoclopramide or prochlorperazine for treatment of headache. RESULTS: A total of 4588 clinical encounters were identified, 2542 with prochlorperazine and 2046 with metoclopramide. One patient had a dystonic reaction with metoclopramide (0.049%). Eleven patients had a dystonic reaction with prochlorperazine (0.43%). The relative risk of a dystonic reaction with prochlorperazine over metoclopramide is 8.85 (95% confidence interval 1.15 to 68.5). There were differences between groups of patients who received metoclopramide versus prochlorperazine in terms of age, number of doses, and coadministration of diphenhydramine. In a logistic regression, administration of prochlorperazine over metoclopramide (P = 0.019) and greater number of doses (P < 0.001) remained associated with acute dystonic reactions. CONCLUSIONS: Dystonic reactions are rare events among pediatric patients treated for acute headache, but are more common with prochlorperazine than metoclopramide.

A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine.

STUDY OBJECTIVE: We compare prochlorperazine 10 mg intravenously versus metoclopramide 20 mg intravenously for the emergency department (ED) treatment of acute migraine. METHODS: This was a randomized, double-blind, clinical trial comparing 2 parenteral dopamine antagonists. Both drugs were administered during 15 minutes with 25 mg intravenous diphenhydramine. Pain scores on a numeric rating scale were assessed at baseline, every 30 minutes for 2 hours, and by telephone 24 hours after discharge. The primary endpoint was the between-group difference in change in numeric rating scale from baseline to 1 hour postbaseline. Secondary endpoints included mean differences in change in numeric rating scale at 2 and 24 hours, headache relief, adverse effects, and desire to receive the same treatment for future migraines. RESULTS: Of 152 patients screened, 97 were eligible and 77 were randomized. The mean change in numeric rating scale scores at 1 hour was 5.5 and 5.2 in subjects receiving prochlorperazine and metoclopramide, respectively (difference=0.3; 95% confidence interval [CI] -1.0 to 1.6). Findings were similar at 2 hours and 24 hours. Forty-six percent (18/39) of prochlorperazine and 32% (12/38) of metoclopramide subjects reported adverse events (difference=15%; 95% CI -6% to 36%). Seventy-seven percent (26/34) of prochlorperazine and 73% (27/37) of metoclopramide subjects wanted to receive the same medication in future ED visits (difference=4%; 95% CI -16% to 24%). CONCLUSION: Either prochlorperazine 10 mg intravenously or metoclopramide 20 mg intravenously, combined with diphenhydramine 25 mg intravenously, is an efficacious treatment for ED patients with acute migraine. Three quarters of subjects in both arms would want the same medication for their next migraine.

In vitro melanogenesis inhibition by fluphenazine and prochlorperazine in normal human melanocytes lightly pigmented.

PURPOSE: Fluphenazine and prochlorperazine as phenothiazine-class antipsychotic drugs are widely used to treat schizophrenia, however their use is associated with significant side effects such as extrapyramidal symptoms, as well as ocular and skin disorders. Our goal was to determine the effect of fluphenazine and prochlorperazine on cell viability and melanogenesis in lightly pigmented normal human melanocytes. METHODS: The viability of melanocytes was evaluated by the WST-1 colorimetric assay, while melanin content and tyrosinase activity were tested spectrophotometrically. RESULTS: It has been shown that both phenothiazines induce the concentration-dependent loss in cell viability. The EC50 values were calculated to be 6.13 and 0.63 µM for fluphenazine and prochlorperazine, respectively. Fluphenazine in the concentration of 5.0 µM and prochlorperazine in concentrations of 0.5 and 0.75 µM decreased melanin content and tyrosinase activity. The observed inhibition of melanogenesis may be explained by the decrease of enzyme activity. CONCLUSIONS: The demonstrated changes in melanization process in lightly pigmented cells exposed to fluphenazine and prochlorperazine in vitro suggest a significant role of melanin and melanocytes in the mechanisms of undesirable side effects of these drugs in vivo. Graphical abstract Fluphenazine and prochlorperazine significantly inhibits melanogenesis in lightly pigmented melanocytes HEMn-LP.