The Effectiveness of Chamomile on Migraine Intensity and Sleep Quality among Children: A Randomized Clinical Trial
Article information
Abstract
Purpose
Evidence suggests that chamomile may be both effective and safe in alleviating migraine symptoms and improving sleep quality in children; however, the results of published studies have been inconsistent. The current study investigated the effectiveness of chamomile—specifically, in Migraphar (Know Tech Phar) herbal capsules—in reducing the severity of migraines and improving sleep quality in children affected by this condition.
Methods
In this clinical study, children experiencing mild to moderate migraines (characterized by mild headaches that allow normal activities, moderate headaches that impede but do not completely halt activities, and severe headaches that completely disrupt activities) were randomly allocated to receive amitriptyline paired with either Migraphar (n=26) or a placebo (n=25) over a 3-month period. Assessments of pain intensity, measured through a visual analog scale, and sleep quality, evaluated using the Pittsburgh Sleep Quality Questionnaire, were conducted both before and after completing the treatment interventions.
Results
No notable difference was observed in the average frequency of headache attacks between the intervention and control groups both before and after completing the treatment protocols. Nevertheless, a significant reduction in the number of attacks was observed in both groups after the intervention. Similarly, no differences were detected in the average sleep quality scores between the two groups before and after the intervention; however, both groups experienced a marked improvement in sleep quality after treatment.
Conclusion
The incorporation of chamomile into the conventional treatment protocol for migraine headaches in children does not alleviate headache intensity or improve sleep quality.
Introduction
Migraine is one of the most common neurological symptoms of chronic pain in children, affecting nearly 10% of those aged between 5 and 15 years, and as many as 28% of adolescents aged 15 to 19 years [1,2]. Without effective treatment, persistent and recurrent headaches can significantly impair family dynamics, lead to school absenteeism, and disrupt work and social relationships. Moreover, childhood migraine carries a substantial risk of becoming a chronic condition that persists into adulthood [3]. Therefore, early intervention is essential to prevent the progression of the disease and to address the tendency for recurrence often encountered in adult patients. The treatment approach for migraines in children is similar to that for adults, encompassing both acute therapies aimed at alleviating migraine episodes and preventive strategies designed to reduce the frequency, duration, and intensity of these attacks [4]. Various pharmacological classes are available for preventive therapy, including antidepressants, anticonvulsants, antihistamines, beta-adrenergic receptor blockers, calcium channel blockers, and botulinum toxin [5,6].
Due to the frequent inadequacies of standard treatments in providing adequate pain relief, patients and their guardians often explore alternative therapeutic options. However, healthcare professionals tend to be cautious about prescribing preventive medications to pediatric patients, primarily due to limited evidence supporting their efficacy and the risk of adverse effects in this population [7]. There is growing interest in natural supplements for managing migraines and headaches. Several studies suggest that these natural therapies can be effective in preventing migraines in children and adolescents, largely due to their minimal side effects, although the existing evidence is somewhat limited [8]. Chamomile, a fragrant herb from the Asteraceae family, is recognized as one of the oldest medicinal plants used by humans, with origins tracing back to ancient Greece [9]. This plant is consistently featured in reputable pharmacopeias, highlighting the therapeutic benefits of its flowers. Chamomile is attributed with a wide array of medicinal properties, serving as a diuretic, expectorant, stomach tonic, carminative, appetite stimulant, digestive aid, choleretic, laxative, antiseptic, analgesic, anti-migraine, antipyretic, anti-gout, anticonvulsant, anti-inflammatory, and anti-itch agent [10-12]. The primary plant parts used for medicinal applications are the dried leaves or aerial components. Recently, there has been growing interest in using chamomile to alleviate headaches and as a preventive measure against migraines [13].
Numerous clinical studies have been conducted to assess the efficacy and safety of chamomile in the prevention of migraines, with the majority of these trials favoring chamomile over a placebo. Additionally, the data indicate that chamomile is generally safe, exhibiting only mild and temporary side effects [14,15]. Research confirms that chamomile is generally safe for use, showing only mild and temporary side effects [16]. The plant’s effectiveness in alleviating migraines has been linked to several mechanisms, including its interaction with gamma-aminobutyric acid and receptors similar to benzodiazepines, the suppression of nitric oxide production, the stimulation of cytokine release, the promotion of serotonin release from platelets, and the inhibition of calcitonin gene-related peptide release from the trigeminovascular system [17,18].
The herbal capsule known as "Migrafar" (Know Tech Phar, Tehran, Iran) is made from the active compounds of plants with the scientific name Tanacetum parthenium and Matricaria chamomilla. In addition to the primary ingredient derived from cow chamomile, Migraphar also incorporates beneficial compounds from the German chamomile plant, or Matricaria chamomilla [19]. This medication is intended for the management of acute migraine episodes and the associated nausea, as well as for the prevention of migraine headaches and alleviation of symptoms during and after menstruation. However, there is limited evidence regarding its efficacy and safety in treating migraine headaches in pediatric patients.
The aim of this study was to evaluate the therapeutic impact of chamomile, as found in Migraphar capsules, on alleviating migraine headaches and addressing sleep disturbances in children.
Materials and Methods
1. Study population
A randomized double-blind clinical trial was conducted at a university clinic in Shahrekord, Iran, involving 52 children diagnosed with migraine headaches. The study took place from 2021 to 2022. Participants met the inclusion criteria if they had a confirmed diagnosis of migraine headaches ranging from mild to moderate intensity. Mild headaches allowed for normal activity, moderate headaches reduced activity without complete cessation, and severe headaches resulted in a total halt of activities [20]. Eligible participants were aged between 6 and 18 years, had no secondary causes for their headaches, and were not taking any other headache medications. Exclusion criteria included any changes in the definitive diagnosis of headaches, use of medications that could affect headache symptoms, lack of parental consent, non-compliance with herbal treatment protocols, allergies to chamomile, the emergence of complications such as gastrointestinal issues or other adverse effects, and a medical history of asthma or heart conditions, including conduction block and heart failure. The study received ethical approval from the Shahrekord University of Medical Sciences under the ethical code IR.SKUMS.MED.REC.1400.009. Details of the study were registered with the Clinical Trial Registration Center of the Iran Ministry of Health and Medical Education, with the registration code IRCT20220124053815N1. Informed consent was obtained from the parents or legal guardians of the patients included (Fig. 1).
Consolidated Standards of Reporting Trials (CONSORT) diagram of the children in the intervention and control groups.
2. Sample size and sampling method
Considering comparable research and the average monthly frequency of headaches, which stands at 16.2±6.7, along with a clinically significant reduction of 12 units in headache occurrences [21], and factoring in a 95% confidence level with a margin of error of 0.01, the required sample size was initially calculated to be 46 individuals. However, to improve the precision of the results, this number was subsequently increased to 52 participants. Participants were selected using convenience sampling, leading to the creation of two groups of 26 individuals each, labeled as the control and intervention groups.
3. Study interventions
Initially, the research objectives and procedures were clearly explained to the parents of the participants. Only those patients whose parents provided comprehensive consent were included in the study. The parents were asked to provide detailed information about their children's medical history and current medications. Additionally, relevant details such as age, sex, previous medical conditions, headache severity, and duration, as well as any accompanying symptoms at the time of referral, were recorded on a checklist. In total, 52 children were enrolled in the study. They were randomly assigned to either the intervention group, which received amitriptyline and Migraphar at a dosage of two capsules per day for 3 months, or the control group, which received amitriptyline with a placebo for the same period. The study compared these two groups based on the variables under investigation. The Migraphar and placebo capsules, identical in shape and packaging, were supplied by Know Tech Phar pharmaceutical company. These capsules contained extracts from the plant scientifically known as T. parthenium and commonly referred to as "feverfew," as well as German chamomile, scientifically named Matricaria chamomilla. The correct administration of the medication was thoroughly explained to the parents of the participating children, who were instructed not to administer any other migraine treatments outside of the physician's recommendations. The study was conducted as a double-blind trial, ensuring that both the researcher responsible for the design and the patients remained unaware of the allocation and randomization processes.
4. Study measurements
The quality of migraine headaches and the status of sleep disorders were evaluated in both groups. Assessments were conducted twice: initially, 1 month prior to the commencement of the intervention (baseline or week 0), and subsequently during the final month of Migraphar treatment (between weeks 8 and 12, specifically at week 12). The frequency of migraine attacks was determined by counting the number of headache occurrences per month. To gauge the severity of headaches, a visual analog scale was employed, which consisted of a 10-cm ruler marked with "no pain" at the left end and "the most severe pain" at the right end. Patients indicated their pain level by placing a mark along the continuum. The pain scale categorized pain levels from 0 to 10, where 0–1 indicated no pain, 2–3 signified mild pain, 4–5 represented moderate pain, 6–7 denoted severe pain, 8–9 reflected extreme pain, and 10 indicated intolerable pain. To assess sleep quality, the Pittsburgh Sleep Quality Questionnaire (PSQI) was employed, comprising 18 questions divided into seven sections. The initial section evaluates mental sleep quality, as indicated by question 9. The second section addresses sleep onset latency, calculated from the average score of question 2 and part A of question 5. The third section pertains to sleep duration, determined by question 4. The fourth section assesses sleep efficiency and effectiveness, which is calculated by dividing the total hours of sleep by the total hours spent in bed, and then multiplying by 100. The fifth section focuses on sleep disturbances, derived from the average scores of question 5. The sixth section examines the use of sleeping medications, as indicated by question 6. Finally, the seventh section evaluates daytime dysfunction, calculated from the average scores of questions 7 and 8. Each question is scored from 0 to 3, and the cumulative average scores from these seven sections yield a total score ranging from 0 to 21, with scores exceeding 5 indicating compromised sleep quality [22]. The Persian version of the PSQI has been validated and shown to possess Cronbach's alpha coefficient of 0.896, indicating reliability, and a correlation coefficient of 0.880, indicating validity [23].
5. Statistical analysis
The findings for quantitative variables were presented as the mean along with the standard deviation. Categorical qualitative variables were reported as counts with their corresponding percentages. The t-test was employed to assess differences in quantitative variables, while the chi-square test was utilized to compare qualitative variables. A significance threshold of less than 0.05 was established. Statistical analysis was conducted using SPSS version 23 software (IBM Co., Armonk, NY, USA).
Results
The study included a total of 52 participants, with 26 assigned to the intervention group and 26 to the control group. However, one participant from the control group withdrew, leaving 51 patients for the final analysis. Evaluations were conducted before the intervention and again 3 months afterward. An analysis of the baseline characteristics of the participants (Table 1) showed that the groups were comparable in terms of sex, average age at the time of intervention, type of headache, and onset timing. Additionally, there were no significant differences in the initial severity of headaches, average age at headache onset, frequency of headache episodes, or sleep quality prior to the intervention. Table 2 provides an overview of the assessments of migraine headaches and sleep quality conducted before and after the intervention. The analysis indicated no significant differences between the intervention and control groups in the average number of headache episodes before and after the treatment protocols. However, both groups saw a notable reduction in the frequency of attacks following the intervention. Similarly, there were no significant differences in average sleep quality scores between the two groups before and after the intervention, yet both groups experienced a marked improvement in sleep quality after the intervention.
Baseline characteristics of the study population
Headache status and sleep quality before and after the intervention
Discussion
This study involved 51 children diagnosed with migraine at Hajar Shahrekord Hospital. Of these participants, 66.7% were female and 33.3% were male, indicating a higher incidence of migraine among girls. The data showed that 80.4% of the children experienced moderate headache severity, while 19.6% suffered from severe headaches. The frequency of headache episodes varied: 41.2% of the children experienced three attacks per month, 9.8% had four, 15.7% had five, 9.8% had six, and 23.5% experienced seven. Before the intervention, both the intervention and control groups reported experiencing headaches three to seven times per month. However, after the intervention, 30.4% of the placebo group and 30.5% of the intervention group reported only one to two attacks per month. Subsequent analyzes showed no significant difference in the average frequency of headache attacks between the intervention and placebo groups, both before and after the intervention. Additionally, the study found that before the intervention, 14 individuals (56%) in the placebo group and 14 individuals (53.8%) in the intervention group reported poor sleep quality. This number remained unchanged after the intervention, with seven individuals from each group continuing to report poor sleep quality. Further examination confirmed that the mean sleep quality in both groups did not show significant changes before and after the intervention. This suggests that the use of Migraphar capsules combined with amitriptyline did not improve either headache frequency or sleep quality.
The diverse biological and therapeutic properties of chamomile have been extensively evaluated, revealing its antibacterial, anti-inflammatory, antispasmodic, and anxiolytic characteristics [17]. These notable benefits are linked to its rich array of chemical constituents, which include sesquiterpenes, flavonoids, coumarins, and polyacetylenes. Furthermore, the flowers of M. chamomilla yield a blue essential oil, present in concentrations ranging from 0.2% to 1.9%; this is attributed to the presence of chamazulene, which has multiple applications [24]. There is evidence supporting the positive effects of chamomile on migraine headaches in both pediatric and adult populations; however, the results from various studies have been inconsistent. Notably, most of these studies have concentrated on the use of topical chamomile solutions as a treatment for migraine headaches. In a study conducted by Zargaran et al. [14], it was reported that 29% of participants were pain-free 2 hours after applying the chamomile solution, compared to only 2% of those who received a placebo. Moreover, sustained pain relief over a 24-hour monitoring period was observed in 74% of the cases treated with chamomile, in contrast to just 10% in the placebo group. The study by Palevitch et al. [25] demonstrated that chamomile administration significantly reduced pain intensity compared to placebo. Additionally, there was a marked decrease in the intensity of common migraine symptoms such as vomiting, nausea, and increased sensitivity to sound and light. When the group receiving chamomile was switched to a placebo, there was an increase in pain intensity and a worsening of related symptoms. Conversely, transitioning the placebo group to chamomile treatment led to reductions in both pain intensity and symptom severity. In a separate study by Pfaffenrath et al. [26], no significant improvement in the intensity or duration of migraine episodes was observed. Their research involved administering CO2 extract from T. parthenium (MIG-99) in varying doses: 2.08 mg (containing 0.1 mg of parthenolide), 6.25 mg (containing 0.5 mg of parthenolide), and 18.75 mg (containing 1.5 mg of parthenolide), to migraine sufferers over a 12-week period. The findings indicated that this extract did not significantly affect the frequency, duration, or severity of migraine attacks compared to a placebo [27]. These findings are consistent with the results of our study.
In a separate investigation conducted by De Weerdt et al. [27] in 1996, migraine sufferers were given a daily capsule of chamomile extract containing 0.5 mg of parthenolide, or a placebo, over a period of 9 months. After this treatment period, a notable improvement was observed; however, there were no significant changes in the severity or frequency of migraine episodes. The conclusions drawn by these researchers are in line with those of our own study. Additionally, a systematic review by Ernst and White [28] in 2000, which included six randomized controlled double-blind trials, provided inconclusive results regarding the efficacy of chamomile in preventing migraine headaches. Among the studies reviewed, two, including one of high quality, showed that chamomile did not effectively reduce the severity or frequency of migraine attacks. In 2004, Pittler and Ernst [29] conducted a meta-analysis of five randomized, double-blind, placebo-controlled trials involving a total of 343 patients. They concluded that there was insufficient evidence to support the efficacy of chamomile in reducing the frequency and intensity of migraine attacks, as well as the occurrence and severity of associated nausea and vomiting [29]. The authors pointed out that variations in drug dosage, treatment duration, formulation type (including hydroalcoholic extract, dry powder, and supercritical CO2 extract), and the concentration of active ingredients could potentially influence the outcomes [30].
Additionally, the pharmacological properties of chamomile in migraine relief have been associated with specific active compounds, such as chamazulene in its essential oil and apigenin, the principal flavonoid in chamomile. These compounds may reduce nitric oxide release by inhibiting the expression of nitric oxide synthase in activated macrophages [31]. Furthermore, flavonoids, including apigenin, are thought to modulate levels of prostaglandin E2, thereby suppressing inflammatory pathways and reducing neuroinflammation in meningeal and dural trigeminal nociceptors [15,32]. The lack of confirmation regarding the efficacy of this substance for treating migraines in the current study can be attributed to several influencing factors. Variations in genetic, environmental, and cultivation conditions may affect the concentration of the plant's active compounds, thereby influencing its medicinal properties. Notably, significant discrepancies in parthenolide levels and bioactive activity have been observed in commercially available products derived from the chamomile plant [33]. Given that the therapeutic benefits of chamomile are primarily associated with products containing parthenolide, it is recommended that manufacturers implement standardization of active ingredients and adopt rigorous quality control measures [33]. Clearly, further investigation is essential to determine the optimal dosage, treatment duration, and effective combinations necessary for standardization and migraine prevention.
The therapeutic effects of chamomile on sleep quality in children have not been conclusively demonstrated [36,35]. While some studies have indicated a positive impact on sleep quality, others have highlighted its effectiveness in addressing insomnia. The observed benefits may be linked to the tranquilizing properties of chamomile, particularly due to its apigenin and flavonoid compounds, which interact with benzodiazepine receptors in the brain [36-38]. Zick et al. [39] discovered that a 4-week course of oral chamomile extract moderately improved sleep issues and daytime functioning, though it had no significant impact on sleep latency or nighttime awakenings. Given the inconsistent findings from previous studies on chamomile's effectiveness in reducing sleep disturbances, further research is needed to investigate its potential benefits for improving sleep quality in children. Additionally, fine-tuning the dosage and methods of administration could greatly improve the therapeutic results. The study had several limitations, including a small sample size, non-compliance by some patients with the prescribed treatment protocols, inadequate follow-up referrals, and improper medication adherence. These factors could have affected the research outcomes. Therefore, it is recommended that additional studies with a larger sample size be conducted to address these issues.
In conclusion, the research findings indicated that both the intervention group, which received amitriptyline combined with Migraphar, and the control group, treated with amitriptyline and a placebo, showed significant improvements in the frequency of headache attacks and sleep quality over the course of the treatment. However, when comparing the rates of headache occurrences and sleep quality before and after the intervention, no significant differences were found between the two groups. This suggests that both treatment regimens were equally effective in reducing headache attacks and improving sleep quality, and that the addition of Migraphar capsules did not provide any additional benefits in these areas.
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Author contribution
Conceptualization: ZL. Data curation: MS, AFB, and MM. Formal analysis: AA. Funding acquisition: AFB. Methodology: AA. Visualization: MMM. Writing - original draft: MS, AFB, and AFB. Writing - review & editing: MMM.
Acknowledgments
The authors would like to thank the Clinical Research Development Unit, Hajar Hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran for their support, cooperation and assistance throughout the period of study.
This study was funded by Shahrekord University of Medical Sciences.