Abstract：Objective To investigate the clinical efficacy of coenzyme Q10 combined with flunarizine in the treatment of migraine. Methods 104 migraine patients admitted to the Third People's Hospital of Mianyang City, Sichuan Province, from January to June 2023 were selected for the study, and were divided into a control group and an observation group using the randomized numerical table method, with 52 cases in each group. The control group was treated with flunarizine, while the observation group was treated with coenzyme Q10 combined with flunarizine, and both groups were treated continuously for 6 months. Compare and analyze the clinical efficacy of the two groups and the occurrence of adverse reactions during the treatment period. Cerebral hemodynamic indexes (mean blood flow velocity of the posterior cerebral artery, mean blood flow velocity of the middle cerebral artery, mean blood flow velocity of the anterior cerebral artery), oxidative stress status (oxidized low-density lipoprotein (ox-LDL), argyrophilic esterase (ArE)), migraine symptoms (duration of migraine attacks, degree of migraine pain) and the incidence of adverse reactions during the treatment period were compared in the two groups before and after 6 months of treatment. Migraine symptoms (migraine attack duration, migraine pain, migraine attack frequency), and migraine pain were assessed using a numeric rating scale (NRS).
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Results After 6 months of treatment, the total clinical effectiveness rate of patients in the observation group was higher than that of the control group, and the difference was statistically significant (P＜0.05). There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P＞0.05). After 6 months of treatment, the average blood flow rate of middle cerebral artery, average blood flow rate of anterior cerebral artery, average blood flow rate of posterior cerebral artery, ox-LDL, frequency of migraine attacks and duration of migraine attacks of the patients in the two groups were lower or shorter than those in the control group, and the differences were statistically significant (P < 0.05). After 6 months of treatment, the PON-1 and ArE of both groups increased compared with the pre-treatment period, and the observation group was higher than the control group, and the differences were statistically significant (P<0.05). The differences in NRS scores between the two groups were not statistically significant when comparing patients before treatment and after 6 months of treatment (P＞0.05). The clinical efficacy of coenzyme Q10 combined with flunarizine in the treatment of migraine is remarkable, which can effectively improve the cerebral hemodynamics and oxidative stress status of the patients, and the safety is good.
Migraine is a common neurological disorder that can lead to severe disability, loss of productivity, and increased economic burden on families and society [1-2]. In China, the prevalence of primary migraine is as high as 23.8% [3]. In China, the prevalence of primary migraine is as high as 23.8% [3], and migraine occurs more often in young and middle-aged people, which can seriously affect the quality of life of patients [4].
At present, there is no cure for migraine, and the main goal of clinical treatment of migraine is to relieve migraine symptoms. It has been reported in the literature that flunarizine is a commonly used drug in the treatment of migraine, which can inhibit the inward flow of excess calcium ions into vascular smooth muscle cells, relieve cerebral vasospasm, improve cerebral blood flow kinetics, and thus effectively relieve migraine symptoms [5-6].
Overseas studies have pointed out that coenzyme Q10 is an antioxidant that can be used to improve the clinical characteristics of migraine [7]. However, there is still a lack of clinical evidence to support the efficacy of coenzyme Q10 in the treatment of migraine in China. Therefore, this study investigated the clinical efficacy of coenzyme Q10 combined with flunarizine in the treatment of migraine and its effect on cerebral hemodynamics, with the aim of providing an evidence-based basis for clinical application.
1 Objects and Methods
1.1 Subject of the study
A total of 104 migraine patients admitted to our hospital from January to June 2023 were selected for the study, and were divided into a control group and an observation group using a randomized numeric table method, with 52 cases in each group. Inclusion criteria:
(1) The diagnostic criteria for migraine are met [8];
② Age 18-80 years old; ③ Duration of the disease ≥ 1 year, frequency of migraine attacks > 2 times / month; ④ No contraindications to the drugs used in this study. Exclusion criteria: ① headache caused by other diseases; ② combined with liquid system diseases or digestive system diseases;
(iii) Combination of other craniocerebral diseases;
④ Combined mental illness;
⑤ Combined serious heart, lung, liver, and kidney dysfunction;
(vi) Combined infectious diseases.
The baseline data of gender, age, disease duration, body mass index, smoking history, alcohol consumption history and comorbidities of the two groups were comparable, with no statistically significant differences (P ＞ 0.05). The study was approved by the Medical Ethics Committee of the Third People's Hospital of Mianyang City, Sichuan Province [Approval No. 2022 (18)], and all patients were informed of the study and signed an informed consent form.
1.2 Methodology
Patients in the control group were treated with oral flunarizine, 5 mg/times, once /d. Patients in the observation group were treated with oral coenzyme Q10 combined with flunarizine, flunarizine 5 mg/times, once /d; coenzyme Q10 10 mg/times, three times /d. Patients in the two groups were treated continuously for 6 months, and were followed up once a week during the treatment period. All patients completed the 6-month treatment, and there was no case dropout. All patients completed the treatment for 6 months, and no case was dropped. During the acute attack of migraine, NSAIDs were given according to the "Chinese Guidelines for the Diagnosis and Treatment of Migraine (2022 Edition)"[8] .
1.3 Observation indicators
1.3.1 Comparison and analysis of the clinical efficacy of the two groups after 6 months of treatment
After 6 months of treatment, cure was defined as complete disappearance of migraine and other clinical symptoms, with no recurrence one month after stopping the drug; significant effect was defined as >75% reduction in the frequency of migraine attacks and >50% shortening of migraine duration; effective was defined as 50%～75% reduction in the frequency of migraine attacks and 25%～50% reduction in migraine duration; and ineffective was defined as <50% reduction in the frequency of migraine attacks and <25% reduction in the duration of migraine [8]. Ineffective is a reduction in the frequency of migraine attacks <50% and the duration of migraine <25% [8]. Total effective rate = (number of cured cases + number of cases with apparent effect + number of effective cases) / total number of cases × 100%.
1.3.2 Comparison and analysis of cerebral hemodynamic indicators before and after treatment in the two groups of patients
The mean blood flow velocity of the posterior cerebral artery, middle cerebral artery, and anterior cerebral artery were measured by Doppler color ultrasonography before and after 6 months of treatment, respectively.
1.3.3 Comparison and analysis of oxidative stress before and after treatment in the two groups of patients
Before and after 6 months of treatment, 5 ml of fasting venous blood was drawn from patients of both groups, and the levels of paraoxonase 1 (PON-1) and oxidized low density lipoprotein (ox-LDL) were measured by enzyme-linked immunosorbent assay; the levels of arylesterase (ArE) were measured by colorimetric analysis. The levels of arylesterase (ArE) were determined by colorimetric analysis.
1.3.4 Comparison and analysis of migraine symptoms before and after treatment of the two groups of patients
The duration of migraine attacks, the degree of migraine pain, and the frequency of migraine attacks were recorded before and after 6 months of treatment, respectively. A numerical rating scale (NRS) was used to assess the migraine pain level of the two groups, and a higher NRS score indicated more severe pain [9].
1.3.5 Comparison and analysis of the occurrence of adverse reactions during the treatment of the two groups of patients
Adverse effects during the treatment period were recorded, mainly including nausea, drowsiness, fatigue, gastrointestinal discomfort, and so on.
1.4 Data analysis and processing
SPSS 27.0 statistical software was used to analyze the data. Measurement data with normal distribution were expressed as "x ± s", and the t-test was used to compare the means between groups; count data were expressed as cases (%), and the χ2 test was used to compare the data between groups. p < 0.05 was regarded as statistically significant difference.
2 Results
2.1 Comparison of the clinical efficacy of the two groups of patients after 6 months of treatment
After 6 months of treatment, the total clinical effectiveness rate of the observation group was higher than that of the control group, and the difference was statistically significant (P < 0.05). The difference was statistically significant (P < 0.05).
2.2 Comparison of cerebral hemodynamic indexes before and after treatment in two groups of patients
Before treatment, there was no statistically significant difference between the mean blood flow velocities of the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery in the two groups (P ＞ 0.05); after 6 months of treatment, the mean blood flow velocities of the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery were lower than those in the control group, with a statistically significant difference (P ＜ 0.05). The differences were statistically significant (P < 0.05).
2.3 Comparison of oxidative stress status between the two groups of patients before and after treatment
Before treatment, there was no statistically significant difference in PON-1, ox-LDL and ArE between the two groups (P > 0.05). After 6 months of treatment, the PON-1 and ArE of both groups increased compared with those before treatment, and the observation group was higher than the control group, with statistically significant differences (P < 0.05); the ox-LDL of both groups decreased compared with those before treatment, and the observation group was lower than the control group, with statistically significant differences (P < 0.05). The difference was statistically significant (P < 0.05).
2.4 Comparison of migraine symptoms before and after treatment between the two groups of patients
Before treatment, there was no statistically significant difference in the duration of migraine attacks, NRS score, and frequency of migraine attacks between the two groups (P ＞ 0.05); after 6 months of treatment, the duration of migraine attacks, NRS score, and frequency of migraine attacks of the two groups were shorter or lower than before treatment, and the duration of migraine attacks and frequency of migraine attacks of the observation group were shorter or lower than that of the control group (P ＜ 0.05). In the observation group, the duration of migraine attacks and the frequency of migraine attacks were shorter or lower than those in the control group, and the differences were statistically significant (P < 0.05). The differences were statistically significant (P < 0.05).
2.5 Comparison of the occurrence of adverse reactions during treatment between the two groups of patients
There was no statistically significant difference in the total incidence of adverse reactions during treatment between the two groups (P ＞ 0.05). See Table 6.
Table 6 Comparison of the occurrence of adverse reactions during treatment in the two groups [cases (%)
3 Discussion
Flunarizine is the first-line drug recommended by the European Headache Consortium for the treatment of migraine, and can reduce the frequency of migraine attacks by more than 50% per month [10]. Previous studies in China have shown that flunarizine can significantly reduce the frequency of migraine attacks, alleviate the pain level, and effectively shorten the duration of migraine attacks [11]. Flunarizine has a strong lipid solubility and can easily cross the blood-brain barrier to act on the cerebral blood vessels, thus inhibiting cerebral vasospasm, and can effectively improve cerebral microcirculation and neuronal metabolism, thus relieving migraine symptoms [12-13]. However, the clinical efficacy of flunarizine alone is limited, and it is often necessary to combine it with other drugs [14].
According to the results of this study, after 6 months of treatment, the total clinical effectiveness rate of patients in the observation group was higher than that of the control group, and the duration of migraine attacks and the frequency of migraine attacks were shorter than or lower than those of the control group, with statistically significant differences. The difference is statistically significant, indicating that the combination of coenzyme Q10 and flunarizine in the treatment of migraine is clinically effective, and can effectively shorten the duration of migraine attacks and reduce the frequency of migraine attacks. Several studies have demonstrated that coenzyme Q10 can directly participate in the reaction of peroxyl radicals, synergize with vitamin E to enhance antioxidant capacity, and enhance human immune function, improve the oxidative state of the brain, and reduce the occurrence of abnormal energy metabolism, thus suppressing migraine attacks and shortening the duration of migraine attacks [15-16]. It has been reported that coenzyme Q10 can effectively reduce the frequency and duration of migraine attacks [17]. A meta-analysis of 371 adult migraine patients showed that coenzyme Q10 could significantly reduce the duration and frequency of migraine attacks [18].
The results of this study showed that after 6 months of treatment, the mean blood flow velocity of middle cerebral artery, the mean blood flow velocity of anterior cerebral artery, the mean blood flow velocity of posterior cerebral artery, and ox-LDL of patients in both groups were lower than or shorter than that of the control group, and the mean blood flow velocity of PON-1, and ArE of patients in both groups were higher than those of the control group, with the difference being statistically significant.
Coenzyme Q10 combined with flunarizine can effectively improve cerebral hemodynamics and oxidative stress in migraine patients. Overseas studies have shown that supplementation of coenzyme Q10 can up-regulate the expression of antioxidant defense system enzymes and inhibit oxidative stress [19].
Studies in China have also shown that coenzyme Q10 can effectively inhibit oxidative stress in the treatment of rheumatoid arthritis and hypertension combined with arrhythmia [20-21]. The results of this study showed that there was no statistically significant difference in the total incidence of adverse reactions between the two groups. This suggests that the safety of coenzyme Q10 combined with flunarizine in the treatment of migraine is better.
In conclusion, the clinical efficacy of coenzyme Q10 combined with flunarizine in the treatment of migraine headache is remarkable, and it can effectively improve the cerebral hemodynamics and oxygenation stress status of the patients, and the safety is good. However, the sample size of this study is small and the follow-up period is short, so the long-term efficacy of coenzyme Q10 combined with flunarizine in the treatment of migraine has not been clarified, and needs to be further investigated in the future.
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