2022 Taiwan Guidelines for Acute Treatment of Migraine.

The Taiwan Headache Society published its guidelines for acute migraine treatment in 2017. Since then, emerging drugs and treatment options have developed rapidly. The migraine-specific drugs gepants and ditans and several noninvasive neuromodulation devices have been approved for use in Europe and the United States. Although not all emerging drugs and treatment options have been approved for use in Taiwan, keeping pace with international trends and updating treatment guidelines are imperative. Therefore, the Treatment Guideline Subcommittee of the Taiwan Headache Society reviewed the quality of recent trials, evaluated the corresponding grade of evidence, and appraised the reported clinical efficacy to reach a new consensus. To ensure that the updated Taiwan guidelines are appropriate and feasible, the subcommittee also referred to the guidelines from the United States, Europe, Canada, and other countries concerning the main roles, recommendation levels, clinical efficacy, and adverse reactions of drugs for the acute migraine treatment. Several types of drugs are currently available for acute migraine treatment in Taiwan. These drugs can be categorized into migraine-specific and migraine-non-specific. Among them, migraine-specific triptans (oral or nasal spray formulations) and migraine-nonspecific acetaminophen and NSAIDs (diclofenac, ibuprofen, naproxen) are highly recommended because they are supported by strong evidence and demonstrate high efficacy. Prochlorperazine injection has been upgraded to a highly recommended level because of the rich clinical experience for this treatment. Ergotamine/caffeine remains a second-line drug because of its lower specificity and efficacy compared with triptans. High-dose aspirin was downgraded to rescue treatment because of potential gastrointestinal side effects. Although evidence supports the combination of oral tramadol and acetaminophen, this combination should be used as a rescue treatment due to concerns about dependence. Evidence supporting the use of intravenous tramadol or morphine is insufficient; therefore, their use is not recommended. As for non-pharmacological approaches, there are only limited controlled data. The choice of treatment for acute migraine attacks should follow the concept of "stratified care." For mild to moderate migraine attacks, oral NSAIDs are the first choice, with combination analgesics, intravenous/intramuscular NSAIDs as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine/caffeine compounds are recommended and should be administered in the early stage of migraine attacks. Antiemetics can be used as supplements to alleviate nausea and vomiting. Other emerging migraine-specific drugs, such as gepants or ditans, may also have a role in the future. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either therapy alone. Parenteral steroids and fluid supply are the first-line treatment for status migrainosus. Acetaminophen is suitable for mild to moderate migraine attacks and remains the first choice for children and pregnant women. To prevent medication overuse headache, the use of acute treatment should be limited to a maximum of 2 days per week. Key words: acute migraine treatment, evidence-based medicine, treatment guidelines, triptans, ergotamine, neuromodulation.

Improving Acute Treatment of Pediatric Primary Headache Disorders With a Novel Headache Treatment Center: Retrospective Review of Preliminary Outcomes.

OBJECTIVE: To determine preliminary outcomes of targeted headache treatments provided at a novel outpatient acute care pediatric headache treatment center. BACKGROUND: Limitations exist in acute management of pediatric headaches, including inadequate access to specialty headache therapies and headache specialists in acute settings, variable success of emergency room treatments, and omission of comfort measures. An outpatient acute headache care clinic (the "Headache Treatment Center") was strategically initiated at a Midwestern pediatric academic hospital to provide acute and targeted headache therapies for children with active headaches. METHODS: We conducted a retrospective chart review of 154 visits from September through November 2018 of patients ages 7-18 years visiting the Headache Treatment Center. RESULTS: On average, headache intensity (measured on an 11-point pain numeric rating scale) decreased after interventions used in the Headache Treatment Center (mean change = 2.85 ± 2.81, P < .05, Cohen d = 1.01). Large effect sizes for reducing headache intensity were observed for pericranial, occipital/auriculotemporal, and occipital nerve blocks, Cohen d = 1.56, 1.64 and 1.02, respectively. Large effect sizes for reducing headache intensity also were observed for a transcutaneous supraorbital nerve stimulator device (Cefaly) (Cohen d = 1.02), acupuncture (Cohen d = 1.09), and intravenous migraine cocktails (Cohen d = 0.91-1.34). CONCLUSION: Targeted headache therapies to abort pediatric primary headaches as part of a novel headache clinic model may be beneficial for short-term management.

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.

The antipsychotic and antiemetic drug prochlorperazine delays the ventricular repolarization of the in situ canine heart.

Electropharmacological effect of the antipsychotic and antiemetic drug prochlorperazine was assessed using the halothane-anesthetized in vivo canine model (n = 5). Up to 10 times higher than the clinically relevant doses of prochlorperazine (< or = 3 mg/kg, i.v.) did not induce cardiohemodynamic collapse in the model. Meanwhile, clinically relevant to supratherapeutic doses (0.3 - 3 mg/kg, i.v.) prolonged the ventricular repolarization period in a dose-related and reverse-use dependent manner that could become proarrhythmic substrates. Thus, caution has to be paid on the use of prochlorperazine particularly for patients with risks of the elevated plasma drug concentration, compromised cardiac repolarization, and/or frequent ventricular premature beats.

P6 acupressure and nausea and vomiting after gynaecological surgery.

We studied the effect of P6 acupressure on 46 women undergoing laparotomy for major gynaecological surgery who received patient-controlled analgesia. Half the patients received acupressure at the P6 site, the remainder received acupressure at a "sham" site. There was a reduction in the requests for anti-emetic therapy in the group receiving P6 acupressure but there was no difference in the incidence of nausea and vomiting. There was no difference in total morphine consumption between the two groups.

Electro-acupuncture and postoperative emesis.

One hundred unpremedicated female patients of ASA grade 1 or 2 who underwent laparoscopy as outpatients were allocated randomly to one of four groups. All patients received general anaesthesia with fentanyl, thiopentone, halothane, nitrous oxide and oxygen; suxamethonium was given to facilitate tracheal intubation. In the recovery room, group 1 (control) received no treatment; group 2 received electro-acupuncture at the P6 point (Neiguan) on the right side for 15 minutes, group 3 received transcutaneous electrical nerve stimulation at the P6 point on the right side for 15 minutes and group 4 received prochlorperazine 5 mg intravenously. Any act of vomiting, including dry retching, during the first 3 postoperative hours was regarded as postoperative emesis. The incidence of postoperative emesis was 11/25 (44%) in group 1, 3/25 (12%, p less than 0.05) in group 2, 9/25 (36%) in group 3, and 3/25 (12%, p less than 0.05) in group 4. Our results suggest that electro-acupuncture is as effective as prochlorperazine, and may be better than transcutaneous electrical nerve stimulation, in reducing postoperative emesis.

Protection against cisplatin nephrotoxicity by prochlorperazine.

Prochlorperazine (Compazine; PCPZ) is often used to limit cisplatin (CDDP)-induced emesis. However, recent studies in mice have shown that PCPZ protects against renal injury produced by treatment with various nephrotoxicants (e.g., MethylCCNU, mercuric chloride). Because renal toxicity remains a serious limitation to the effective use of CDDP, we conducted the present study to determine whether PCPZ could also protect against CDDP-induced renal injury. PCPZ treatment was shown to ameliorate CDDP-induced renal lesions in both rats and mice at doses and treatment schedules that were comparable with those used for alleviating chemotherapy-induced emesis. A PCPZ dose of 10 mg/kg x 2 offered complete protection against CDDP-induced increases in blood urea nitrogen (BUN) levels in mice, with significant protection occurring at a PCPZ dose as low as 5 mg/kg. Similarly, PCPZ ameliorated CDDP-induced increases in BUN, glucosouria, and enzymuria in F344 rats. PCPZ treatment did not affect the urinary excretion or renal tissue levels of total platinum or the plasma pharmacokinetics of free platinum. However, it did cause a marked reduction in the concentration of total plasma platinum (free platinum + protein-bound platinum). PCPZ was not found to affect the in vivo antitumor activity of CDDP against P388 leukemia. The present study suggests that PCPZ may be of therapeutic benefit when used with CDDP and provides a rational basis for the selection of antiemetic therapy.

Effects of extracellular calmodulin and calmodulin antagonists on B16 melanoma cell growth.

Two drugs known to inhibit the action of calmodulin, prochlorperazine offP) and N-(6-aminohexyl)-5-chloro-1-napthalene sulfonamide (W7), were investigated for their ability to control cell proliferation in murine B16 melanoma cells in culture. PCP and W7 inhibited [3H]thymidine uptake in these cells, 50% inhibition occurring with 13 microM PCP and 40 microM W7. In the presence of relatively high concentrations of fetal calf serum (FCS), cells withstood high concentrations of both drugs (100 microM PCP and 200 microM W7) and showed increased pigment production. Drug-inhibited DNA synthesis could be reversed by the addition of fresh medium containing FCS or by the addition of exogenous pure calmodulin. Extracellular calmodulin itself stimulated DNA synthesis. FCS was found to contain calmodulin-like activity at concentrations that may be relevant to the stimulation of [3H]thymidine uptake by cells in culture.

The Controlled Substances Therapeutic Research Act in the state of Washington.

In March 1979, the Governor of the State of Washington signed legislation establishing a THC/marihuana research program within the Washington State Board of Pharmacy. By November 1980, approximately 80 physicians had enrolled more than 400 patients on the chemotherapy protocol which randomly assigned subjects to receive either THC and prochlorperazine or THC and placebo. This report describes the process of implementing the legislation, the administrative and clinical roles of project personnel, and the design of three currently operating protocols.