Archives of Academic Emergency Medicine. 2022; 10(1): e27 OR I G I N A L RE S E A RC H Efficacy of Sumatriptan/Placebo versus Sumatrip- tan/Propofol Combination in Acute Migraine; a Random- ized Clinical Trial Reza Farahmand Rad1, Akram Zolfaghari Sadrabad1, Mohammadali Jafari2, Marziyeh Ghilian3∗ 1. Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. 2. Emergency Department, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 3. Emergency Department, Mehriz Fatemeh Zahra Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Received: February 2022; Accepted: March 2022; Published online: 14 April 2022 Abstract: Introduction: Migraine headaches can cause severe pain for patients and lead them to multiple visits to the emergency department (ED). This study aimed to evaluate the efficacy of propofol + sumatriptan combination in comparison with sumatriptan alone in the management of acute migraine headaches. Methods: This triple- blind clinical trial involved patients who referred to two emergency departments with acute migraine headaches. Patients were randomly assigned to control (sumatriptan and placebo) or intervention (propofol and sumatrip- tan) groups for comparison of the efficacy and side effects of treatment. Results: In this study, 60 patients were included whose mean age was 31±8.8 years, and headaches were more common among women. After 30 and 60 minutes from the beginning of treatment, the mean pain score reduction in the intervention group was sig- nificantly greater than that in the control group (p=0.012, p=0.024). In addition, the rate of chest tightness in the control group was significantly higher than the intervention group. The absolute risk reduction of adverse events (Chest tightness, Bradycardia, hypotension, and etc.), in patients with acute migraine headache taking propofol and sumatriptan treatment, was 32.18% (95% CI: 8.02 – 56.35). Conclusion: This study supports the use of propofol for treatment of acute migraine headaches and shows that combining sumatriptan with propofol is more effective in relieving migraine headaches and the associated symptoms than using sumatriptan alone. However, more studies with longer follow-ups are still needed. Keywords: Migraine disorders; headache; sumatriptan; propofol; pain management Cite this article as: Farahmand Rad R, Zolfaghari Sadrabad A, Jafari M, Ghilian M. Efficacy of Sumatriptan/Placebo versus Suma- triptan/Propofol Combination in Acute Migraine; a Randomized Clinical Trial. Arch Acad Emerg Med. 2022; 10(1): e27. https://doi.org/10.22037/aaem.v10i1.1510. 1. Introduction There are more than 1.2 million emergency department vis- its for migraine headaches each year in the United States (1, 2); this disease is more common in women than in men (3). Migraine is a chronic multifaceted disease that mani- fests as a one-sided, throbbing headache, nausea, vomiting, photophobia, and phonophobia (4). Diagnostic criteria in- clude headaches lasting at least 4 hours for at least 15 days ∗Corresponding Author: Marziyeh Ghilian; Emergency Medicine Depart- ment, Mehriz Fatemeh Zahra Hospital, Central Administration, Bahonar Sq., Yazd, Iran. Postal code: 8916978477, Email: marziehghilian@yahoo.com, Tel: +989134545004, Fax number: +98 35 38282682, ORCID: http://orcid.org/0000- 0002-4716-6257. of the month, according to the International Classification of Headache Disorders (5). Although the International Headache Society (IHS) recom- mended acetaminophen, NSAIDs, triptans, and steroids for migraine headaches (6), none of these have been found to fully relieve migraine pain or lead to the desired clinical re- sults (7). There are many migraine treatments available, but side effects and contraindications are two issues that we con- stantly deal with. Interestingly, it seems that combinations of drugs can be effective for treating migraines (8). Sero- tonin receptors play an important role in the pathogenesis of migraine headaches. The most important challenges in using sumatriptan are its side effects and limitations. Since it is an effective and selective agonist for the vascular 5- hydroxytryptamine receptor subtype, it is relied upon to treat This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem R. Farahmand Rad et al. 2 migraine attacks (9). In migraine, sumatriptan reduces some clinically important symptoms in two ways: first, it facili- tates blood vessel contraction in certain parts of the brain as a 5HT 1B vascular receptor agonist; and second, it limits the breakdown of vasoactive neuropeptides. Propofol also af- fects gamma-aminobutyric acid (GABA) receptors, prevent- ing pain signals from reaching these receptors and signifi- cantly reducing pain scores in migraine patients (10). Propo- fol reduces migraine pain by acting on GABA receptors (11), and this mechanism may be suitable for combination ther- apy (12). Studies performed as clinical trials are few and the amount of propofol used varies widely, from a fixed amount based on weight to a constant amount of bolus. In general, propofol reduces pain and reduces headache recurrence, but some studies have shown that pain scores do not differ signif- icantly between groups despite propofol being more effective than placebo (13). The present study’s purpose was to compare the efficacy and adverse effects of sumatriptan + propofol combination with sumatriptan alone for controlling acute migraine headaches in patients who referred to the emergency department (ED). 2. Methods 2.1. Study design and setting This triple-blind randomized clinical trial with a parallel design was performed in the emergency departments of Shahid Sadoughi and Shahid Rahnemoun Hospitals, affili- ated to Yazd University of Medical Sciences, Yazd, Iran, dur- ing one year. Using a table of random numbers, the par- ticipants were randomly allocated to sumatriptan + propo- fol or sumatriptan and placebo groups and the efficacy and side effects of treatment were compared between two groups. All the participants gave their informed consent to enter the study. This study was approved by the Ethics Committee of Yazd University of Medical Sciences under the code IR.SSU.MEDICINE.REC.1393.81 and was registered in the Iranian Registry of Clinical Trials under the code IRCT2015050422089N1. 2.2. Participants The study population included patients with an acute attack of migraine headache who either had a migraine headache previously diagnosed by a neurologist or met the migraine headache criteria, based on the International Headache As- sociation (IHS) definition, and were between 18 and 45 years old. Cases with diagnosis of acute attack of non-migraine headache, refusal to participate in the study, pregnancy and lactation, cardiovascular diseases, drug addiction, diastolic blood pressure above 105 mmHg, cerebrovascular diseases, receiving ergotamine 24 hours before visiting the ED, egg al- lergies, ocular migraine, vestibular dysfunction, and hemi- plegia were excluded. 2.3. Intervention After allocation of eligible patients to case or control groups, all patients underwent cardiac monitoring and pulse oxime- try and non-invasive measurement of blood pressure. Intra- venous (IV ) route was established for each case with angio- catheter gage 20. Pain intensity was measured for all patients, by an emergency medicine specialist using a visual analog scale (VAS), on arrival to ED. Sumatriptan (6 mg in 0.5 ml) was injected subcutaneously (SC) and propofol (0.5 mg per kg body weight) was adminis- tered as a slow infusion for 1 hour. Propofol and placebo were administered using a microset containing 100 ml of normal saline coated with an aluminum coating; to prevent the pain caused by propofol injection and to maintain study blind- ness, both drugs were administered to all the participants with 1 ml of 2% lidocaine via angiocath. All the injection pro- cedures were performed by a nursing expert in the presence of an emergency medicine specialist. Pain was measured by an emergency medicine specialist every 30 minutes for up to one hour after administration of the drug in each group. All the patients were evaluated for recurrence and side effects of medications 2 hours after receiving the drug. During the injection procedures, the patients were examined for any side effects and the drug was discontinued if any complication occurred. The final evaluation was performed one hour after the drug injection. The satisfaction of all the drug recipients was recorded. After one hour, if the patient’s pain reduction was less than 4 points, the response to med- ication was recorded as incomplete and Ketorolac or opium was injected as rescue pain reliever for these patients. 2.4. Outcome Success rate of pain management and the rate of compli- cation were the primary measured outcomes of study. To measure the pain severity, visual analogue scale (VAS) was used. Nausea, chest tightness, chest pain, neck and throat pain, ear discomfort, dysphagia, muscle weakness, warmth, paresthe- sia, cramps and burning, toothache, dizziness, meningitis, injection site pain, hypertension (blood pressure≥140/90 mmHg) and hypotension (systolic blood pressure<90 mmHg), and in rare cases, sudden death and MI were con- sidered as the most probable side effects of sumatriptan (14-17). Probable side effects of propofol were considered to be respiratory depression (respiratory rate <12), apnea (Apnea is defined as a respiratory pause longer than 20 seconds), hypoxemia (O2 saturation below 90%), hypotension, brady- cardia (heart rate <60 beat/min, myoclonus), pain during injection (18-22). This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2022; 10(1): e27 Figure 1: Receiver operating characteristic (ROC) curve of alveolar arterial gradient (best cut-off = 0.28; area under the curve (AUC) = 0.602) and respiratory index (best cut-off = 0.28; AUC = 0.522) in predicting the mortality of COVID-19 cases. Table 1: Comparing the baseline characteristics of studied cases between intervention (sumatriptan and Propofol) and control (sumatriptan and placebo) groups Variable Intervention (n=29) Control (n=30) P Age (year) 32.3 ± 9.5 29.7 ±8.1 0.26 Gender Male 9 (31.0) 7 (23.3) 0.56 Female 20 (69.0) 23 (76.7) Headache duration (hour) 5.1 ± 5.7 4.8 ±5.5 0.89 Presenting pain score# 9.1 ± 0.9 8.9 ± 0.7 0.27 Positive family history* 18 (62.1) 17 (56.7) 0.42 Migraine Type Common 28 (96.5) 26 (86.7) 0.61 Classic 1 (3.5) 4 (13.3) Presenting symptoms Photophobia 28 (96.6) 25 (83.3) 0.19 Nausea 24 (82.8) 26 (86.7) 0.73 Vomiting 12 (41.4) 18 (60.0) 0.19 Phonophobia 5 (17.2) 7 (23.3) 0.75 Data are presented as mean ± standard deviation or number (%). #: based on visual analogue scale. *: family history of migraine headache. 2.5. Blinding In this study, blinding was performed at the following three levels: patients, researcher, and data processor. The drugs were pre-prepared by the study’s lead researcher and admin- istered based on the kind of the group they belonged to. The specialist who recorded the severity of the pain, did not know the type of drug received. The data analyzer was unaware of the type of drug given to each group. 2.6. Statistical analysis The sample size was determined to be 60 people, 30 people for each group, considering a significance level of 5%, a test power of 80%, a standard deviation of 1.3 for pain score, and with one unit difference between the mean pain score in the This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem R. Farahmand Rad et al. 4 Table 2: Comparing symptom relief and adverse outcomes of treatments between intervention (sumatriptan and propofol) and control (sumatriptan and placebo) groups Variable Intervention (n=29) Control (n=30) P Pain relief# 30 minutes 4.6 ± 2.9 6.9 ± 1.8 0.024 1 hour 2.2 ± 2.7 5.5 ± 2.6 0.012 Other symptoms’ relief Photophobia 24 (82.8) 8 (26.7) 0.001 Nausea 22 (75.9) 14 (46.7) 0.033 Vomiting 9 (31.2) 5 (16.7) 0.232 Phonophobia 3 (10.3) 1 (3.3) 0.353 Ondansetron requirement Number (%) 7 (24.1) 24 (80.1) 0.001 Recurrence of symptom Number (%) 10 (34.5) 6 (20.0) 0.254 Adverse outcomes Chest tightness 0 (0.0) 20 (66.7) 0.001 Bradycardia and hypotension 7 (24.1) 0 (0.0) 0.05 Other adverse effects 3 (10.3) 0 (0.0) 0.49 Data are presented as mean ± standard deviation or number (%). #: based on visual analogue scale. two groups (23). The analyses were performed using SPSS version 15 (SPSS Inc., Chicago, IL, USA). Chi-square test was used to analyze the baseline nominal results. ANOVA test was also performed for comparing age and time interval between the onset of headache and referral to the emergency department between the two groups. Comparison of the effects of the drugs in the two groups on reducing pain (every 30 minutes after the treatment) was performed using the Paired Couple test. Val- ues of P <0.05 were considered as statistically significant dif- ferences. 3. Results 3.1. Baseline characteristics of studied cases In this study, 109 patients with headache complaints were evaluated during a one-year period. Finally, 68 patients who met the inclusion criteria were enrolled in the study. Nine pa- tients were excluded after enrolment (eight due to lack of co- operation in providing the necessary information during per- forming the intervention, and one due to the decreased oxy- gen saturation to less than 80% after drug administration in the intervention group). Therefore, 29 and 30 patients were evaluated in the intervention group and the control group, respectively (Figure 1). Table 1 compares the baseline characteristics of studied cases between intervention and control groups. The mean age of the patients in the intervention and control groups was 29.5±32.3 and 29.7±8.1 years, respectively (p = 0.26). The two groups were similar regarding gender distribution (p = 0.56), duration of headache (p = 0.89), presenting pain score (p = 0.27), positive family history of migraine headache (p = 0.42), migraine type (p = 0.61), and type of presenting symptoms (p > 0.05). 3.2. Response to treatment Table 2 compares the rate of symptom relief and side effects between the groups. The mean reduction in pain score in the intervention group 30 minutes (4.6 ± 2.9 vs. 6.9 ± 1.8; p = 0.024) and 60 minutes (2.2 ± 2.7 vs. 5.5 ± 2.6; p = 0.012) af- ter treatment was greater than the control group. The rate of recovery of other symptoms was higher in the intervention group but the difference in recovery rate was statistically sig- nificant only regarding photophobia (82.8% vs. 26.7 %; p = 0.001) and nausea (75.9% vs. 46.7%; p = 0.033). The num- ber of the patients requiring anti-nausea injection was sig- nificantly less in the intervention group (24.1% vs. 24 80%; p = 0.001). 3.3. Side effects of treatment Feeling of chest tightness was significantly observed in the control group (66.7%), which disappeared after 15 minutes, but in the intervention group, this complication was not re- ported (p=0.001). However, hypotension and bradycardia occurred significantly more in the intervention group com- pared to the control group (p = 0.05). In addition, weakness, drowsiness, and dizziness were seen in almost all the patients included in the intervention group, all of which resolved after drug administration and did not differ significantly from the control group. The absolute risk reduction of adverse events (Chest tight- ness, Bradycardia, hypotension, and etc.), in patients with This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 5 Archives of Academic Emergency Medicine. 2022; 10(1): e27 acute migraine headache taking propofol and sumatriptan treatment, was 32.18% (95% CI: 8.02 – 56.35). 4. Discussion The results of this study indicated a significantly greater im- provement in symptoms associated with migraine headache as well as in pain score in the intervention group compared to the control group. These results suggest that the combi- nation of propofol and sumatriptan results in a synergistic effect on controlling migraines, and that the side effects of sumatriptan like chest tightness, have reduced following the administration of a lower dose of the drug. In addition, this drug combination caused no new side effects for the patients in the intervention group. Krusz et al. (24) examined the role of intravenous propofol in treatment of migraine headaches and showed that the mean reduction in headache severity was 95.4% after an average of 20 to 30 minutes of intravenous propofol treatment with an average dose of 110 mg bolus. However, in Krusz’s study, 86% of the patients had either nausea or vomiting at the time of propofol administration, or had both of them, which spon- taneously resolved after the administration with no medica- tion, possibly within 3 to 5 minutes due to bolus adminis- tration (24). In contrast, in our study, the patients did not experience any symptoms of nausea or vomiting due to the slow infusion. They have also stated that propofol, does not cause hemodynamic instability in patients receiving it, which may be due to the fact that the prescribed dose is less than the dose prescribed for anesthesia. In the present study, the patients in the intervention group experienced no hemody- namic instability, which could be due to a lower dose than the sedative dose and slow infusion of the drug. However, two patients in Krusz’s study and one patient in the present study were excluded due to the decreased oxygen saturation. In krusz’s study, three recurrences were reported on the day af- ter performing the treatment (24). In that study, recurrence of headache was reported after 72 hours in both groups, which was higher in the group receiving sumatriptan and placebo. This difference in recurrence rate may be due to administrat- ing the drug via slow infusion and concomitant use of suma- triptan, which have led to a longer effect of the drug. In a study by Soleimanpour (25), who compared the effects of propofol with dexamethasone on migraine, it was found that propofol could reduce pain more rapidly (within 10 minutes), while the pain relief in the dexamethasone group reached the equivalent of propofol after 20 minutes. Also, patients receiv- ing propofol showed fewer side effects compared to the con- trols and recurrence of refractory migraine has also reduced (25). In the present study, the rate of pain score reduction in the intervention group was similarly higher than the control group. In a double-blind clinical trial conducted by Robert et al. (26), propofol was not superior to placebo in the early relief of headache; however, propofol was superior to placebo in re- ducing the severity of headache, which differed from the re- sults obtained in this study. In Robert’s study, intralipid was used as a placebo. In addition, no other drug has been used with propofol (26). In most cases, several analgesics were used to treat migraine headaches, especially refractory and high-intensity headaches. It is also true that intralipid is not known to be effective on treating migraines, but it contains some substances such as soybean oil, egg lectin, and glycerol, which is like an emulsion used as a basis for propofol (27). In addition, each of these substances can exacerbate migraine headaches, and there also are many challenges to propofol emulsions (28). In a study by Mitra et al. (29), which was an open-label, ran- domized controlled pilot trial, they compared the procedu- ral dose of propofol (1 mg/kg body weight) with the stan- dard treatment chosen by the physician to control migraine headaches. Accordingly, the study reported that propofol ad- ministration finally resulted in faster pain relief and shorter discharge times in patients with migraine headaches (29). In our study, pain reduction was similarly greater in the inter- vention group. Furthermore, in Mitra’s study, similar to the present study, only one patient experienced a decrease in saturation during propofol administration, which improved with oxygen uptake and no other side effects were reported. On the other hand, in that study, the procedural dose of propofol was used as a bolus injection and the maximum time to achieve optimal consciousness was 5 hours (29), but in the present study, none of the patients included in the intervention group entered the anesthesia phase due to the use of doses less than sedatives, concomitant use with other analgesics, and slow infusions. Clinical practice guidelines vary for migraines. It is possi- ble that the discrepancies observed when comparing with other instructions may be due to intravenous analgesia be- fore reaching the emergency room. However, propofol, due to its clinical effect and immune profile in the adult popu- lation, appears to be a promising drug in the treatment of migraine in ED. Based on the available evidence, propofol is a suitable treatment for pain relief and a last resort, espe- cially for patients with refractory or incurable migraines, or in patients who have contraindications to the repeated use of first-line drugs, and it can be considered as a good alternative treatment. This study also showed that other drug combina- tions should be considered for the treatment of migraine be- cause it seems that the drugs can improve each other’s effect and impose fewer side effects on patients by administrating lower doses of each one of these drugs, so they can benefit more from their enhanced therapeutic effect. Finally, we sug- gest that the therapeutic effects of propofol and its effect on This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem R. Farahmand Rad et al. 6 the interval between the onsets of the next migraine attack be studied through long-term follow-up of patients. 5. Limitations Follow-up was performed by telephone and based on the pa- tient’s statement, so there was no specific clinical criterion for recurrence. Some patients may have used painkillers be- fore the visit, which did not have a significant effect on the results due to the measurement of pain score, as an objec- tive criterion, as well as the rate of reduction of this score after starting the treatment. After enrolment, eight partici- pants were excluded because they failed to cooperate in pro- viding the necessary information and another was excluded because their oxygen saturation was less than 80% following the intervention. 6. Conclusion Our results support propofol as a treatment for acute phase migraine and show that a combination of sumatriptan and propofol is more effective in relieving migraine headaches and their side effects compared to sumatriptan alone. 7. Declarations 7.1. Acknowledgments We are thankful to all of the participants for their coopera- tion. 7.2. Authors’ contributions Based on the recommendations of the International Com- mittee of Medical Journal Editors, all authors passed four cri- teria for authorship contribution. 7.3. Funding and supports There is no funding and support. 7.4. Conflict of interest All authors confirm thet there is not any financial and per- sonal relationships with other people or organizations that could inappropriately influence (bias) their work. References 1. Wu J, Davis-Ajami ML, Kevin Lu Z. Impact of depression on health and medical care utilization and expenses in US adults with migraine: a retrospective cross sectional study. Headache: The Journal of Head and Face Pain. 2016; 56(7):1147-60. 2. Delavar Kasmaei H, Amiri M, Negida A, Hajimollarabi S, Mahdavi N. Ketorolac versus Magnesium Sulfate in Mi- graine Headache Pain Management; a Preliminary Study. Arch Acad Emerg Med. 2017; 5(1):e2. 3. Burch R. Antidepressants for preventive treatment of mi- graine. Curr Treat Options Neurol. 2019; 21(4):18. 4. Salmito MC, Duarte JA, Morganti LOG, Brandão PVC, Nakao BH, Villa TR, et al. Prophylactic treatment of vestibular migraine. Braz J Otorhinolaryngol. 2017; 83:404-10. 5. Cady R, Saper J, Dexter K, Manley HR. A Double- Blind, Placebo-Controlled Study of Repetitive Transnasal Sphenopalatine Ganglion Blockade With T x360 as Acute Treatment for Chronic Migraine. Headache: The Journal of Head and Face Pain. 2015; 55(1):101-16. 6. Deen M, Martinelli D, Pijpers J, Diener H-C, Silberstein S, Ferrari MD, et al. Adherence to the 2008 IHS guide- lines for controlled trials of drugs for the preventive treat- ment of chronic migraine in adults. Cephalalgia. 2019; 39(8):1058-66. 7. Khazaei M, Mir NHN, Aghdam FY, Taheri M, Ghafouri- Fard S. Effectiveness of intravenous dexamethasone, metoclopramide, ketorolac, and chlorpromazine for pain relief and prevention of recurrence in the migraine headache: a prospective double-blind randomized clini- cal trial. Curr J Neurol. 2019; 40:1029-33. 8. Tobin MJ. Basing respiratory management of COVID-19 on physiological principles. Am J Respir Crit Care Med. 2020;201(11):1319-20. 9. Deen M, Hougaard A, Hansen HD, Schain M, Dyssegaard A, Knudsen GM, et al. Association between sumatriptan treatment during a migraine attack and central 5-HT1B receptor binding. JAMA neurology. 2019; 76(7):834-40. 10. Jesani J, Simerson D. Pharmacologic management of acute migraines in the emergency department. Adv Emerg Nurs J. 2019; 41(2):150-62. 11. Sheridan DC, Hansen ML, Lin AL, Fu R, Meckler GD. Low- dose propofol for pediatric migraine: a prospective, ran- domized controlled trial. jem-journal. 2018; 54(5):600-6. 12. Cisewski DH, Motov SM. Essential pharmacologic op- tions for acute pain management in the emergency set- ting. Turk J Emerg Med. 2019; 19(1):1-11. 13. Piatka C, Beckett RD. Propofol for treatment of acute mi- graine in the emergency department: a systematic re- view. Academic Emergency Medicine. 2020; 27(2):148-60. 14. Ferrari MD, Saxena PR. Clinical and experimental effects of sumatriptan in humans. Trends Pharmacol Sci. 1993; 14(4):129-33. 15. Solomon S, Lipton RB, Newman LC. The site of common side effects of sumatriptan. Headache: The Journal of Head and Face Pain. 1997; 37(5):289-90. 16. Brar Y, Hosseini SA, Saadabadi A. Sumatriptan. Stat- Pearls. Treasure Island (FL): StatPearls Publishing 2022. 17. Ron Walls RH, Marianne Gausche-Hill. Rosen’s Emer- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 7 Archives of Academic Emergency Medicine. 2022; 10(1): e27 gency Medicine: Concepts and Clinical Practice. 9th ed. Philadelphia: Elsevier; 2017 March 9, 2017. 18. Kotani Y, Shimazawa M, Yoshimura S, Iwama T, Hara H. The experimental and clinical pharmacology of propo- fol, an anesthetic agent with neuroprotective properties. CNS Neurosci Ther. 2008; 14(2):95-106. 19. Marik PE. Propofol: therapeutic indications and side-effects. Current pharmaceutical design. 2004; 10(29):3639-49. 20. Folino TB, Muco E, Safadi AO, Parks LJ. Propofol. Stat- Pearls. Treasure Island (FL): StatPearls Publishing. 21. Judith Tintinalli OJM, Donald Yealy, Garth Meckler, J. Stapczynski, David Cline, Stephen Thomas Toxicology, Opioids. In: Tintinalli JE, editor. Tintinalli’s Emergency Medicine and Comprehensive Study Guide 1: Mc Graw Hill; 2020. p. 1234. 22. Roberts J. Roberts and Hedges’ Clinical Procedures in Emergency Medicine and Acute Care. Philadelphia: El- sevier; 2017 December 12, 2017. 1500 p. 23. Moshtaghion H, Heiranizadeh N, Rahimdel A, Esmaeili A, Hashemian H, Hekmatimoghaddam S. The efficacy of propofol vs. subcutaneous sumatriptan for treatment of acute migraine headaches in the emergency depart- ment: A double-blinded clinical trial. Pain practice. 2015; 15(8):701-5. 24. Krusz JC, Scott V, Belanger J. Intravenous propo- fol: unique effectiveness in treating intractable mi- graine. Headache: The Journal of Head and Face Pain. 2000;40(3):224-30. 25. Soleimanpour H, Taheraghdam A, Ghafouri RR, Taghizadieh A, Marjany K, Soleimanpour M. Improve- ment of refractory migraine headache by propofol: case series. International Journal of Emergency Medicine. 2012; 5(1):19. 26. Meek R, Graudins A, McDonald M, McGannon D, Limm E. Comparing propofol with placebo for early resolu- tion of acute migraine in adult emergency department patients: A double-blind randomised controlled trial. Emerg Med Australas. 2020; 33(3): 465-472. 27. Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia : an international journal of headache. 2010;30(7):829-37. 28. Baker M, Naguib M. Propofol: The Challenges of Formu- lation. Anesthesiology. 2005;103:860-76. 29. Mitra B, Roman C, Mercier E, Moloney J, Yip G, Khullar K, et al. Propofol for migraine in the emergency depart- ment: A pilot randomised controlled trial. Emerg Med Australas. 2020; 32(4):542-7. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Methods Results Discussion Limitations Conclusion Declarations References