Abstract
Background:
Refugees and war survivors are at higher risk of developing mental health disorders. Anxiety and stress are caused by many factors, including a stressful environment that could cause fatigue and low quality of life. Despite the existence of many synthetic anxiolytic and antidepressant drugs, symptom management has still not been successful. Ginkgo biloba extract has been used as one of the potential herbal remedies to enhance cognitive functions. Psycho-education plays a significant role in alleviating psychological distress. However, the role of G. biloba in alleviating anxiety, stress and fatigue among refugees was not well studied previously.
Objectives:
In this study, we aimed to compare the effect of G. biloba and psycho-education with only psycho-education on refugees’ anxiety, stress and fatigue.
Methods:
A randomized controlled, pre-test–post-test design was used. Data were measured at baseline and 6 weeks later.
Results:
Providing psycho-education for the control group showed a non-significant improvement in outcome variables. However, adding G. biloba to psycho-education for the experimental group showed a significant reduction in mental, physical, activity fatigue and anxiety.
Conclusion:
The addition of G. biloba to the psycho-education proved superior to psycho-education alone. Therefore, combining the two approaches is beneficial in alleviating anxiety and fatigue.
Introduction
Higher anxiety and stress are risk factors for mental health disorders that have a negative impact on the quality of human life. 1 Traumatized refugees and war survivors are at higher risk of developing mental health disorders. 2 War refugees are at risk of mental health disorders such as anxiety, post-traumatic stress disorder and depression, which may be induced by displacement, trauma experience, low economic status, limited access to healthcare services, and higher rates of infectious and chronic diseases. 2 Mental health status is often overlooked in refugees on their arrival in host countries. Most efforts are focused on physical health issues and chronic disease management.3,4 Anxiety and stress are caused by many factors, including a stressful environment that could affect some biological mechanisms, which may lead to fatigue and poor quality of life, 5 subsequently making treatment options more complex, with reduced health outcomes. 6
Symptom management has still not been successful, despite the existence of many synthetic anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). 7 Furthermore, these drugs have side effects which makes searching for further safe treatments essential. 8 Accordingly, different adaptogens have been introduced to treat anxiety and stress. Plants known for their tonic activity in traditional medicine are among these adaptogens.9,10 In Chinese medicine, Ginkgo biloba (Ginkgoaceae) has been used to treat short-term memory loss, vertigo and lack of attention. 11
Recently, G. biloba extract has been used as one of the potential herbal remedies to enhance cognitive functions and to treat Alzheimer’s disease and the symptoms of cerebral insufficiency.9,12,13 G. biloba extract is derived from the dried leaves of the ginkgo tree, where the standardized plant extract contains 24% ginkgo–flavonglycosides and 6% ginkgo–terpenoid lactones as active constituents. 14
Psychotherapeutic interventions carried out by trained healthcare professionals such as psychologists and nurses are frequently based on a cognitive-behavioural approach. 15 The goals of this intervention are to treat distress, enhance behaviour and lifestyle, and promote personal awareness, social status and personal growth. There are many types of therapeutic strategies, including psychodynamic, behavioural and psycho-educational. 16
Psycho-education plays a significant role in anxiety treatment. 17 Psycho-education sessions have proved to be effective in treating distressed subjects, especially among refugees suffering from post-traumatic stress disorder (PTSD) and anxiety. 18 Although different studies have examined the anxiolytic effects of G. biloba in animal models and humans,7,13 no studies have examined the role of a G. biloba combination with psycho-education in reducing anxiety, stress and fatigue compared with psycho-education alone among refugees. Although, anxiety and stress have a negative effect on the quality of life (QOL) and are considered a major cause of disability, 1 no final treatment was developed due to the sophisticated pathophysiology of anxiety and stress. In addition, to the best of our knowledge, this is the first report that concerns the role of G. biloba in alleviating anxiety, stress and fatigue among refugees. Therefore, the primary objective of the current study was to compare the effect of G. biloba and psycho-education versus psycho-education alone on refugees’ anxiety, perceived stress and fatigue.
Methods
Design
We wanted to examine the changes in anxiety, perceived stress and fatigue among refugees treated by G. biloba and psycho-education sessions, as compared with refugees receiving psycho-education sessions alone. A randomized controlled, pre-test–post-test design was used. The participants were randomly selected and assigned either to the experimental or control group. The control group comprised Iraqi refugees receiving weekly supportive psycho-education sessions by licensed psychotherapists with nursing and psychology backgrounds. The experimental group received G. biloba tablets and the weekly supportive psycho-education sessions.
Sample, sampling technique and setting
A computer-generated list was utilized to select a simple random sample of refugees attending Caritas clinics in three different cities in Jordan. The inclusion criteria for participants were: Iraqi refugees in Jordan, aged 18 years and older, and agreement to participate in the study. The exclusion criteria were: pregnant women (due to possible hormonal interactions with G. biloba 19 ), participants on antiplatelet or anticoagulant therapy; 20 participants with a previous hypersensitivity history for G. biloba; and those who had previously received psycho-education; herbal medicine and drugs used to treat anxiety, stress and fatigue.
The assignment of participants either to the experimental or control group was carried out by sequencing participants to odd and even numbers to decide whether to add G. biloba or not. The study participants were Iraqi refugees, recruited from three Caritas medical centers: Amman, Madaba and Zarqa. Each of these Caritas medical healthcare centers provides primary healthcare services for around 100 individuals each day.
G* Power software 21 (Dusseldorf university, Dusseldorf, Germany) was used to calculate sample size. A medium-effect size of 0.50, power level of 0.80, and conventional α = 0.05 two-tailed criterion of the significance were applied to determine the required sample size. Accordingly, a minimum of 34 participants were required in each group. To manage the problem of participant attrition, the researcher decided to include a total of 99 participants to overcome the issue.
Data collection procedure
Once the permission to conduct the study was obtained, the researchers recruited 105 participants using a simple random sampling technique. Out of this total, 99 agreed to participate in the study. The participants were then randomly assigned to either the experimental (n = 50) or control group (n = 49). Written information sheets were provided and explained by the researchers. Consent forms were obtained from all eligible and willing participants.
The study instruments to measure anxiety, stress and fatigue were distributed to both groups at the baseline as a self-completing questionnaire in Arabic language. However, for illiterate participants, one of the study researchers read the questions and the options, asking participants to select the most appropriate choice.
The participants who completed the questionnaire at baseline did not know their group assignments, but the researcher distinguished the groups in which they were included. Participants were informed of their groups before the beginning of the session. A code number was assigned to each participant in the experimental and control groups to conceal their involvement, as well as to keep their records confidential.
On the same day as the baseline, the experimental group received the psycho-education session and one capsule of G. biloba extract of 120mg. The G. biloba was given daily to the participants for 6 weeks. The control group received only the psycho-education session. The psycho-education session was conducted once weekly for both the experimental and control groups over the 6 weeks.
The study question packs to measure anxiety, stress and fatigue were collected 6 weeks later to measure anxiety, stress and fatigue at individual appointments at healthcare centers. The participants were contacted between May and August 2016.
Psycho-education sessions
The Caritas psycho-education unit organized regular psycho-education focus group sessions in Arabic language. The teaching materials were all adapted from the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). The sessions were conducted for both the experimental and control groups (n = 99) and each session involved around 10 participants. The sessions included psycho-education for the management of anxiety, stress and fatigue, such as relaxation exercises, physical and social activities, pain and cognitive functions. 18 Participants attended a total of six sessions and each session lasted for 90 minutes (Fig. 1).

Flow diagram of the study.
Ginkgo biloba
G. biloba is commonly used among the elderly to enhance the cognitive function and relieve fatigue. Refugees who were eligible and willing to participate in the study were randomly selected and assigned to the experimental group. They received a consultation with a pharmacist for the G. biloba uses, dosage and possible contraindications. Participant adherence was controlled by phone reminder. G. biloba extract is considered safe with a side-effect profile similar to a placebo. Occasionally, it may cause mild skin allergies, stomach upset, headache, dizziness and constipation. 20 The G. biloba could be withdrawn in case of side effects. Participants were instructed to refer to the chief pharmacist in cases of unwanted side effects.
The G. biloba (Gincata®, Delass Natural Products Company, Amman, Jordan) used in the current study is a tablet-dosage form, manufactured by wet granulation, drying, milling and then compression. A standardized dry-extract method was used for G. biloba extraction. The dried herb dose was 4.2–8.0 grams, which is equivalent to 120mg extract. The standardization included total flavonoglycosides: 22–27%, total terpene lactones: 5.4–12.0%, ginkgolides a, b, c: 2.8–6.2%, bilobides: 2.6–5.8% and the ginkgolic acid < 5ppm. The expiates used were microcrystalline cellulose, sodium starch glycollate and magnesium stearate.
Study instruments
In addition to a demographic data sheet, which included sex, marital status, level of education, work and ability to read and write, the Hamilton Anxiety Rating Scale (HAMA), Perceived Stress Scale (PSS) and Multi-Dimensional Fatigue Inventory (MDFI) were collected at baseline and 6 weeks later.
Hamilton Anxiety Rating Scale
For the purpose of measuring anxiety level among participants, the Arabic version of HAMA was used. This scale was developed to measure the severity of anxiety symptoms. 22 It consists of 14 items; each has five choices ranging from 0 (not present) to 4 (severe). The total score ranged from 0 to 56. Previous research showed good validity and reliability. 23 In the current study, the scale showed adequate reliability with a coefficient alpha of 0.87.
Multi-Dimensional Fatigue Inventory (MDFI)
The MDFI includes 20 items that measure five dimensions of fatigue: general fatigue, physical fatigue, mental fatigue, reduced motivation and reduced activity. 24 Each dimension is represented by four items, with total scores ranging from 4 to 20, with a higher score indicating greater fatigue. Each item has five options ranging from 1, ‘Yes, that is true’ to 5, ‘No, that is not true’. The instrument was found to have good internal consistency, with an average Cronbach’s alpha coefficient of 0.84. 25 In the current study, the scale showed adequate reliability with a coefficient alpha of 0.91.
Perceived Stress Scale (PSS)
To assess stress level among participants, the Arabic version of PSS was used. This scale was developed to measure stress in 14 items with four Likert points from 0 (never) to 4 (frequent). 26 The total score ranged from 0 to 56 with higher scores indicating greater stress. Previous literature showed adequate reliability of the scale. 4 The current scale showed adequate reliability with a coefficient alpha of 0.84.
Ethical consideration
The study was approved by the American University of Madaba Ethical Review Board and Caritas administration. All recruited participants signed an informed consent form before participation. The participation was wholly voluntary and the participants were guaranteed that their replies were confidential. The participants were told that they could withdraw from the study at any point in time. They were also informed that demographic data and information relating to anxiety, stress and fatigue would be collected from them twice. In addition, the process of the data collection was explained to all participants, and information relating to the estimated amount contact time and the frequency of contact with the participants was given.
Data analysis
Statistical Package of Social Science (SPSS) version 21 statistical software (Multinational technology company, New York, United States) was used to analyse the data. Demographic data were analysed using mean (M), standard deviation (SD) and frequency. An independent t-test was used to examine the differences in age, anxiety, stress, and fatigue subscales, between the control and experimental group. A Chi-square test (i.e. Fisher’s exact test used in the case of less than five represented in any category) was also used to examine the differences in the remaining demographics. The paired t-test was used to examine the changes in anxiety, stress and fatigue for each experimental and control group, the paired t-test was used. Significant level was set for less than 0.05.
Results
Out of the 115 participants approached, 105 were eligible and 99 were willing to participate in the study. A total of 84 participants were included in the analysis, 40 in the experimental group, and 44 in the control group. No adverse events were observed or reported by study participants (Figure 1).
The study sample consisted of males (n = 43, 51.2%), females (n = 41, 48.8%), married (n = 37, 44%), able to read and write in the Arabic language (n = 76, 90.47%), had a university degree (n = 33, 39.1%), and did not have a job during the data collection time (n = 44, 52.32%). The mean age of participants was 39.49 (SD = 5.26) years (Table 1).
Demographics and differences based on demographics at baseline.
At baseline, the differences between the two groups were measured. The t-test showed no significant differences between the two groups based on age. The Chi-square showed no significant difference between the two groups based on sex, marital status, employment status, ability to read, and education level (Table 1). These results indicated that the two groups were homogenous in terms of demographics. Moreover, the independent t-test indicated that there were no significant differences in stress, and fatigue subscales between the experimental and control group except anxiety; the experimental group had a significant higher score at baseline compared with the control group (t = (82) = 12.23, p = 0.04).
A paired sample t-test was conducted to evaluate the changes in anxiety, stress and fatigue scores between the baseline and follow up, for both the experimental and the control groups, one at a time. There was a significant decrease in anxiety (p = 0.001), physical fatigue (p = 0.001), mental fatigue (p = 0.001) and reduction in activity fatigue (p = 0.041) scores at follow-up, as compared with the baseline in the experimental group receiving G. biloba with psycho-education (Table 2). Furthermore, there was no significant difference in all measures from baseline time to follow-up time for the control group. A slight improvement that did not reach statistical significance was seen in anxiety and in the mental fatigue domain (p = 0.09; Table 2).
Differences in stress, anxiety, and fatigue scores for the control and treatment group.
SD, standard deviation.
Discussion
The main purpose of this study was to compare the effect of G. biloba and psycho-education, as opposed to psycho-education alone on refugees’ anxiety, perceived stress and fatigue. In the current study, psycho-education helped improve slightly the anxiety and mental fatigue; however, these improvements were not significant. A similar recent study 18 concluded that psycho-education in refugees produced a limited effect. This may be attributed to the short-term intervention. Indeed, outcome measures were taken only after 6 weeks, which may not allow for subjective improvements among displaced refugees that would require a longer duration of intervention. 27
The addition of G. biloba leads to significant improvement in anxiety and some of the fatigue symptoms. Traditionally, G. biloba has been used as a nootropic and antioxidant agent in cerebrovascular insufficiency, mainly in patients with cognitive impairment. 28 Recent evidence has demonstrated the anxiolytic effect of G. biloba. 29 In the present study, the daily intake of 120mg G. biloba for 6 weeks reduced anxiety scores in a group of refugees, consistent with previous research. 29 In a 4-week randomized controlled trial, G. biloba demonstrated anxiolytic effects in a dose-dependent manner using 240 mg and 480 mg of G. biloba. 30 Our study has a similar protocol; however, there are some differences, such as the type of study sample, dose used and the follow-up period. Our study is the first to examine the anxiolytic effect of G. biloba on refugees, who are at high risk of developing anxiety. This is due to the impact of the stressful environment, which makes them an attractive model for investigation. In our study, we found a similar HAMA score reduction (14 points) to a previous study, 30 despite using a lower dose. This could be attributed to the longer follow-up period in our study.
The current study showed a positive effect of adding G. biloba to psychotherapy on anxiety. Impairment in monoamine neurotransmitters (i.e. serotonin, dopamine) in the hypothalamus and the mesolimbic system is strongly believed to be associated with anxiety and mood disorders.5,29 A possible explanation for the study result is that long-term use of G. biloba increases monoamine neurotransmitter levels, thus enhancing mood. 31 Another hypothesis for anxiety pathophysiology is oxidative stress. 32 It is evident that G. biloba plays a fundamental antioxidant role;33,34 this effect may be associated with the anxiolytic actions in the study sample.
Several studies have investigated the role of G. biloba in improving physical fatigue. It has been shown that G. biloba improves fatigue symptoms, physical endurance and the activities of daily living.35,36 Refugees are at high risk of developing physical fatigue that can limit their daily activities due to the lack of: adequate and healthy food, comfortable accommodation, medications, sleeping hours, and of having a poor life quality.1,37,38 No previous studies have investigated the role of G. biloba in refugees. In the current study, the use of G. biloba in refugees reduced the physical fatigue and improved the reduced activity score. The possible mechanism for enhancing physical activity of G. biloba is its antioxidant effect that protects erythrocytes from damage, therefore allowing higher oxygen supply and energy production. 39 G. biloba has been globally prescribed in cerebral insufficiency that is associated with cognitive dysfunction, which is clinically manifested as dementia and lack of concentration, especially in healthy volunteers, the elderly and patients with Alzheimer’s disease. 40 In this study, refugees are more likely to experience mental fatigue possibly due to displacement difficulties and several post-migration stressors.4,41 The mental fatigue subscale of the MDFI used in this study focuses mainly on the ‘ability to concentrate’, which was significantly improved after 6 weeks of G. biloba administration. A possible explanation for the improvement of mental fatigue symptoms in the study sample is the potent antioxidant and the cerebrovascular perfusion enhancing effects exerted by G. biloba. 6
The study has some limitations such as the limited number of participants and the relatively short period of intervention and follow up. Moreover, the participants were only recruited from three cities in Jordan and among Iraqi refugees only, which may affect the generalizability of the study results.
Recommendations and implications
This study has direct implications for healthcare professionals (including physicians, pharmacists, nurses and psychologists) in providing psycho-education in combination with herbal medicine that has a beneficial effect on lowering anxiety and fatigue among refugees. A further randomized controlled trial is recommended with a larger sample that represents all geographical areas in Jordan, and includes Syrian refugees, as that would help improve the generalizability of the findings. The present study could be considered as a baseline against which to conduct future research studies to address the gaps and the limitations of the current study.
Conclusion
G. biloba, in addition to psycho-education was effective in reducing anxiety-, physical- and mental-fatigue scores after 6 weeks, thus augmenting the psychotherapeutic intervention. The findings of our study support the use of the herb with psycho-education, to yield significant improvements in a short period of time among war refugees.
Footnotes
Acknowledgements
Special thanks to Caritas social workers. Also, the authors thank our senior students Eliia Ejelat and Elias Saffori for their work and dedication. The corresponding author thanks Rafael and Dr G Moscati for their support. Also, thanks to the Dellas Company for donating the Gincata samples. The authors contributed the following: Ahmed Mohammad Alsmadi: study planning, data collection, data analysis and interpretation, and manuscript writing up; Loai. Issa. Tawalbeh: study planning, data collection, and manuscript writing up; Omar Salem Gammoh: study planning, data collection, data analysis and interpretation, and manuscript writing up; Waleed Zalloum: study planning, data interpretation, and manuscript writing up; Ala Ashour: study planning, data collection, and manuscript writing up; Hrayr Attarian: study planning, data analysis, and manuscript writing up; Mohammad Qassem Shawagfeh: study planning, data collection, data analysis, and manuscript writing up.
Funding
The study was funded by the American University of Madaba.
Conflict of Interests
The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
