Critical Literature Review

Introduction

This review uses a CONSORT scoring framework to evaluate various studies and make a report that critically analyses the studies in a linear and clear manner. CONSORT scoring based on the adapted CONSORT framework for Herbal Medicine (Gagnier et al., 2006); See Appendix 3, Table 2 for pictogram and key of how trials were scored. The evaluation specifically focused on the following sections: study samples, interventions, findings and outcome measurements, and ethical issues.

Study samples

All the studies generally recruited samples from health centres. The subjects’ age ranged from 2 to 17 years (6-13 years in Uebel-von Sandersleben et al 2014), (6-12 years in Shakibaei et al 2015), (6-14 years in Lyon et al 2001), and (3 – 17 years in Salehi et al 2010). Tse et al (2018) argued that age-related variance is important in evaluating in the adverse events because old patients and children are more susceptible to adverse event in similar clinical trials. Similar remarks were made by Luo et al (2016), who noted that patients between the age of 50-59 years old, and 0-9 years old are more likely (a probability of 31.4%) to experience unfavourable health changes in clinical trials compared to subjects of age between 20-25 years old, whose probability of experiencing unfavourable health changes stand at 20.8%. Therefore, the age criteria help in identifying and assessing a clinical trial’s safety. All the studies reported relatively dissimilar distribution of male and female subjects in both intervention and control groups as follows 75% male and 25% female in Uebel-von Sandersleben et al 2014, 38% female and 72% male in Shakibaei et al (2015), 78% male and 32%female in Lyon et al (2001). Salehi et al (2010) did not highlight their gender distribution. A common inclusion criterion across all the studies were children with symptoms of ADHD based on DSM-IV assessment. Uebel-von Sandersleben et al 2014 included children diagnosed with ADHD who did not tolerate or were unwilling to take methylphenidate while Shakibaei et al 2015 included children and adolescents diagnosed with ADHD. The other two studies (Lyon et al 2001 and Salehi et al 2010) included children with ADHD. Uebel-von Sandersleben et al 2014 excluded children with children who missed to participate (N=1), those who withdrew their consent (N=2), and those who were susceptible to a secondary disporder (N=1). Shakibaei et al 2015 did not indicate their exclusion criteria while Lyon et al 2001 excluded children who did not display any ADHD symptoms before 7 years of age even if they had previously been diagnosed with any mental disorder involving substance abuse, psychosis or bipolar effective disorder. Lastly, Salehi et al 2010 excluded children who had a history of any pervasive developmental disorder, if they had any psychiatric problem that required a pharmacotherapy, any risk of mental retardation and those who had any suicide risks.

The use of age

All the studies generally recruited samples from health centres. The subjects’ age ranged from 2 to 17 years (6-13 years in Uebel-von Sandersleben et al 2014), (6-12 years in Shakibaei et al 2015), (6-14 years in Lyon et al 2001), and (3 – 17 years in Salehi et al 2010). Tse et al (2018) argued that age-related variance is important in evaluating in the adverse events because old patients and children are more susceptible to adverse event in similar clinical trials. Similar remarks were made by Luo et al (2016), who noted that patients between the age of 50-59 years old, and 0-9 years old are more likely (a probability of 31.4%) to experience unfavourable health changes in clinical trials compared to subjects of age between 20-25 years old, whose probability of experiencing unfavourable health changes stand at 20.8%. Therefore, the age criteria help in identifying and assessing a clinical trial’s safety. Age is especially a significant factor in ADHD because studies have established patterns of age in the UK’s prevalence of ADHD. For instance, Alqahtani (2010) reported that symptoms of ADHD tend to be noted at an early age and they become more evident when there are changes in the child’s circumstances, such as when the child is beginning to go to school. As such, according to Limenez et al (2017), most children are diagnosed with ADHD when they are of the age between 6 to 12 years old. Similarly, as per Morgan et al (2014), the symptoms of ADHD do improve with age, even though those who are diagnosed with it at a younger age tend to continue experiencing the problem (Bonati et al, 2018). All the studies reported relatively dissimilar distribution of male and female subjects in both intervention and control groups as follows 75% male and 25% female in Uebel-von Sandersleben et al 2014, 38% female and 72% male in Shakibaei et al (2015), 78% male and 32%female in Lyon et al (2001). Salehi et al (2010) did not highlight their gender distribution. A common inclusion criterion across all the studies were children with symptoms of ADHD based on DSM-IV assessment. Uebel-von Sandersleben et al 2014 included children diagnosed with ADHD who did not tolerate or were unwilling to take methylphenidate while Shakibaei et al 2015 included children and adolescents diagnosed with ADHD. The other two studies (Lyon et al 2001 and Salehi et al 2010) included children with ADHD. Uebel-von Sandersleben et al 2014 excluded children with children who missed to participate (N=1), those who withdrew their consent (N=2), and those who were susceptible to a secondary disporder (N=1). Shakibaei et al 2015 did not indicate their exclusion criteria while Lyon et al 2001 excluded children who did not display any ADHD symptoms before 7 years of age even if they had previously been diagnosed with any mental disorder involving substance abuse, psychosis or bipolar effective disorder. Lastly, Salehi et al 2010 excluded children who had a history of any pervasive developmental disorder, if they had any psychiatric problem that required a pharmacotherapy, any risk of mental retardation and those who had any suicide risks.

Interventions

The present study investigates evidence on the efficacy and safety of Ginko Biloba for ADHD. All the reviewed studies used standardized preparations of Ginko Biloba except Lyon et al 2001 who used a mixture preparation of Panax quinquefolium and Ginkgo biloba. Uebel-von Sandersleben et al 2014 used tablets of EGb 761®, which contains dry extract of Ginko biloba leaves and acetone 60% (w/w). an initial dose of 40 mg twice daily was administered while successfully increasing the doses to 60 and 120 mg twice daily depending on the tolerability and efficacy observed during the weekly dosage visits. Shakibaei et al 2015 used an extract of Ginko biloba leaves standardized by 24% flavonoid glycoside and 6% terpene lactone. They also used water and ethanol as solvents in a 4:1 herbal to extract ratio (Ginko T.DTM). The participants underwent a two-week baseline drug free period after which, all the children received methylphenidate in a total dosage of 20 mg per day (for those with <30 kg of body weight) and 30 mg per day for those with a body weight of >30 kg. the researchers then gradually increased the dosage by 10 mg per week until the date of total dosage. Salehi et al 2010 et al also used Ginko T.D.™ tablets containing 40 mg of dried Ginko biloba extracts. For standardization, Ginko T.D.™ was titrated in the trial with the following specifications: for the first week, 40 mg per day were used while in the second week, 80 mg per day were used. The subjects received 1 capsule of Ginko T.D.™ in the mording and another capsule of Ginko T.D.™ at midday. In the third week, children of less 30kg weight received 120mg per day. On the other hand, Methylphenidate was titrated based on the following schedule: during the first day, 10 mg was administered, while during the second week, 30 mg was administered per day. During the third week, children of more than 30 kg received 30 mg daily. Lyon et al 2001 used AD-FX capsules administered twice a day before patients could eat anything. the capsule contained a combination of 200mg Panax quinquefolium and 50mg of Ginkgo biloba extract. Lyon et al 2001 did not give much information about the drug standardization compared to the other three studies. In most cases, standardization of Gonko Biloba is meant to assure quality, reproductivity and safety of the herb as highlighted by (Ahmed et al, 2017). in a similar study to examine the safety and tame the wild complexity of herbal drugs, Ahmed et al (2017) noted that the standardization process should give much attention to the herbs’ active constituents, bearing in mind unlikeliness that all the constituents will be standardized. On the same note, existing research that all medicines that originate from plants should meet some basic safety and effectiveness requirements. For instance, the World Health Organization WHO (1996) states that the standardization process entails a variety of scientific investigations that involves various biological, chemical and physical evaluation. Uebel-von Sandersleben et al (2014) reported 6 dropouts with no reports of earlier effort to improve compliance. Meanwhile, there was no difference between those who dropped out and those who complied to the end of the study, indicating that the non-compliance did not significantly interfere with the study outcomes. Similarly, Salehi et al (2010) reported two drop outs from the G.biloba group and 2 from the methylephenidate group due to lack of parents’ collaboration. Lyon et al (2001) reported dropouts from 3 participants four weeks into the study, with no reports of prior efforts to promote compliance. Uebel-von Sandersleben et al (2014) did not report any cases of dropouts.

Outcome measures and behavioral scales

The studies used different outcome measures and behavioral scales. For instance, at baseline, Uebel-von Sandersleben et al (2014) measured subjects’ impulsiveness and hyperreactivity using the DISYPS-KJ FBB-HKS scale while the children’s aggressiveness behavior was measured using the FBB-SSV scale. For secondary outcome measures, Uebel-von Sandersleben et al (2014) used a Continuous Performance Test consisting of a sequence of bold black letters presented with a stimulus onset asynchrony of 1650 ms at the center of a 17" CRT monitor against light gray background for 150 ms each. On the other hand, Shakibaei et al (2015) conducted physical examination on each child as well as an evaluation of cardiovascular health using a a standard 12-lead electrocardiogram. Salehi et al (2010) used both parent and teacher ADHD rating scales to measure the symptoms at baseline and after the intervention. Shakibaei et al 2015 also used Children’s global Assessment Scale to measure the general mental and psychosocial health of the children. Nonetheless, side effects were assessed by a psychiatrist at the second and sixth week of the treatment (Shakibaei et al 2015), by a Side Effects Rating Scale (Uebel-von Sandersleben et al 2014), by a checklist that comprises 20 side effects including psychic, neurologic, autonomic and other side effects, administered by a child psychiatrist on days 7, 21and 42 (Salehi et al 2010). Lyon et al 2001 did not report criteria for measuring side effects but identified several adverse events from the study medication. All the studies, including Lyon et al 2001 relied on the DSM-IV scale to measure ADHD. The DSM-IV is a widely used scale for assessing all the ADHD symptoms through two sub-scales namely hyperactivity-impulsivity and inattention subscales. Response to each of the 18 items are graded from 0 (to denote never) to 3 (to denote always). While the total scores range for each subscale range from 0-27, the overall score ranges from 0-54. All the studies used a comparison of symptoms at baseline and after the intervention to ascertain the effectiveness and efficacy of Ginko biloba as a treatment intervention for ADHD. Uebel-von Sandersleben et al 2014 used changes in the behavioural rating scales between pre-treatment to post treatment assessments to ascertain the efficacy, while Shakibaei et al 2015 considered at least 27% symptom improvement from baseline to post-treatment assessment as a sign of treatment efficacy and effectiveness. Results by Uebel-von Sandersleben et al 2014 indicated a possible improvement in quality of life after the administration of EGb 761®. Furthermore, the study found statistically significant improvements in core ADHD symptoms as well as an improvement in the CPT performance. This led to the conclusion that a maximum dosage of 240mg of EGb 761® per day can be used a alternative treatment for children with ADHD. Shakibaei et al 2015 found that compared to the control group (placebo), symptom improvement was observable with regards to parenting inattention score measured by the ADHD-RS-IV. Similarly, the researchers found symptom improvement regarding teacher rating inattention score – leading to a conclusion that Gonka biloba is an effective alternative treatment for ADHD in children. Salehi et al 2010 found significant difference between the intervention group and the control group in terms of the Teacher and Parent rating scores. Compared to the baseline, the changes at endpoint for Ginko T.D.™ was −6.52±11.43 (mean±S.D.) while the changes for methyphenidate were −15.92± 11.44 (mean±S.D.); for Oarent Rating Scale. In the Teacher Rating Scale, the changes at endpoint compared to baseline were −0.84±6.79 (mean±S.D.) for Ginko T.D.™ and −14.04±8.67 (mean±S.D.) for methyphenidate. There was no significant difference in the frequency of side effects between Ginko T.D.™ and methylphenidate groups. These results led to the conclusion that Ginko biloba was less effective in treating ADHD compared to methylphenidate. Lastly, the results by Lyon et al 2001 showed that the proportion of subjects with a reduction in ADHD symptoms (a decrease in T-scores by at least 5 points) ranged from 31% of those who had anxious or shy characteristics to 67%of those who had psychosomatic attributes. On the other hand, the proportion of subjects who improved in terms of social problems attributes ranged were 44% while those who had DSM-IV hyperactive-impulsive attributes and Conner’s ADHD index improved by 74%. The findings suggested that AD-FX intervention may be used as a treatment for ADHD.

Trial design and sample size

Based on Kirkham et al’s (2018) observations that randomized control trials are the best for assessing the efficacy and effectiveness of medical interventions, the present study chose to include only randomized control trials for analysis. Even though a small sample size can facilitate a quick process of enrolment, biochemical analysis, patient review and response to questionnaires (Gamble et al, 2017), a significant limitation of small sample size studies, according to Heyrana et al (2018), is with the large standard of error, imprecise results, lack of a firm conclusion and a wide confidence interval (95% CI). Among the selected studies, Uebel-von Sandersleben et al 2014 had the smallest sample size of 20. No study reported any significant dropouts that could affect the study validity. Similarly, no study reported any change in the study design. All the studies did not report any serious side effects except Shakibaei et al 2015 who reported loss of appetite (6.4%), diarrhea, headache and nausea (12.9%).

Randomization

The most significant trademark for randomized control trials is randomization. According to Piantadosi (2017), the randomization principle minimizes the difference between the treatment groups at the beginning of the trials to identify whether the drug was truly effective when used on that group. Intervention studies that lack randomization are inherently weak in terms of the validity of the statistical test used identify significance (Zwierzyna et al, 2018). That said, Heyrana et al (2018) insisted that “the difference between two randomized sample groups should be same as the difference between two random samples from the same population compared to what would be expected in the population by chance” (Heyrana et al 2018, pp. 22). Two of the four studies randomized and described their randomization procedures to demonstrate the validity of their findings. Uebel-von Sandersleben (2014) used a small sample size and therefore could not use placebo and control groups, neither did they randomize. Shakibaei et al 2015 double blinded and randomized the subjects using two parallel arms. The randomization was done through a software table that used two alphabets to randomly assign between consecutive numbers. Salehi et al 2010 also randomized, double blinded and used parallel groups of subjects. Lyon et al 2001 used an open study design.

Blinding

Piantadosi (2017) defined blinding as the concealment of a group allocation from one or more study subjects. This is completely different from allocation concealment which seeks to avoid selection bias during randomization and recruitment (Piantadosi, 2017). According to Salehi et al (2010), blinding seeks to avoid performance and ascertainment bias after the process of randomization. The two randomized control trials made efforts to ensure complete blinding. For instance, Salehi et al 2010 blindly administered the drugs during titration. Similarly, the patients and parents in the study by Salehi et al 2010 were blind to group assignments. Shakibaei et al 2015 did not give further information about their blinding process despite indicating that the study was a double blinded placebo-control trial. However, none of the two studies that used placebo control thrived enough to discuss the outcome of their blinding process.

Ethical issues

While discussing ethical issues in clinical trials, Gamble et al (2017) acknowledged the notion that those who take the risk to engage in clinical trials are not the same people who reap the benefits participating in those trials. The participants run the risk of potential exposure to unexpected adverse events that are of a greater health hazards than that of a normal clinical care. Uebel-von Sandersleben et al 2014 reported a 0.004 incident rate of adverse events per observation day without any serious side effects while the intervention group in the study by Salehi et al 2010 reported fewer adverse events compared to the control group. Lyon et al 2001 reported adverse events in the form of more emotional and impulsive episodes, with no serious side effects. On the other hand, Shakibaei et al (2015) reported some side effects in The Ginko Biloba group including headache, nausea, loss of appetite, constipation, abdominal pain and diarrhoea. The side effects reported on the placebo group included diarrhoea, nausea, loss of appetite, abdominal pain, constipation palpitation and headache. These side effects (on both treatment and placebo groups) were mild and limited. The principle of beneficence requires doctors and researchers to do no harm – which is also a significant portion of the Hippocratic oath. However, in actual practice, doctors mostly encounter situations that require a compromise between harm and benefit, especially during drug therapy and interventional procedures. But these procedures should always be biased towards ‘benefit’. Therefore, in a practical setting, it is acceptable to engage in a high risk therapy after the individual has been fully informed of the risks. In paediatric practice, one of the ethical principles to be observed is the respect of the individual’s autonomy, which implies that all participants are free to take an independent and active role in making decisions about their participation (Roth-Cline et al, 2011). To achieve this, patients must fully understand and be informed the implications of their medical conditions, complications, and treatment outcomes. However, in practice, children are not able to a true informed consent and therefore rely on adults for guidance. According to Kodish (2003), this situation increases the researchers’ responsibility to acquire true informed consent, although from third parties. All the studies reported informed consent from participants before the trial begins. A summary of all trials Generally, all the trials were of good quality and competence even though as afore-mentioned, issues with sample size (Uebel-von Sandersleben 2014) and blinding (Shakibaei et al 2015), and this may have shallowed the results. All the four studies demonstrated significant effect of G.biloba reducing the symptoms of ADHD, and this included the two studies (Shakibaei et al 2015; Salehi et al 2010) with the largest sample size. One study (Salehi et al 2015) compared the effectiveness of Ginko biloba on ADHD symptoms the effectiveness of methylphenidate in treating ADHD and found that Ginko biloba was less effective in treating ADHD than methylphenidate. The length of treatment and outcome measurement was flexible across all the studies and the applicability of the various outcome measures to identify the effects of Ginko biloba in the treatment of ADHD needs further evaluation. The symptoms of ADHD can present in subjective ways, justifying the choice of different outcome measurement techniques used across the four studies.

Discussion

While there is no significant difference in the findings between the four studies, a few issues need to be addressed to develop more proper conclusions. The following section discusses those issues.

Assessment of study methodology

Original inclusion

Originally, this study report sought to rely on a strict inclusion criterion. However, several limitations were encountered regarding the available number of RCTs that met the inclusion criteria. Consequently, several adjustments were made to include studies with different study designs (open single-centre study by Uebel-von Sandersleben et al 2014, RCT by Shakibaei et al 2015, RCT by Salehi et al 2010, and open single-centre study by Lyon et al 2001), yielding only two RCTs for inclusion. However, the inclusion of studies with different designs made the report more versatile in terms of the evidence it presents. Whereas tailored treatment and dosage are the best ways to assess the effectiveness sand efficacy of herbal therapies and that RCTs are not the best way to evaluate the result of herbal interventions, Gamble et al (2017) suggested that RCTs may work perfectly well in accounting for subject heterogeneity and evaluate the statistical significance. Through RCTs, researchers can report a population’s main tendencies towards the intervention and help the deduction of conclusion from the population on which the study was conducted. Still, open studies are useful backup for RCTs in producing evidence on efficacy and effectiveness of interventions (Zwierzyna et al, 2018). One study (Lyon et al 2001) highlighted the synergistic properties of herbal medicine, which brings out an interesting topic of discussion herein. Whereas the one drug one target approach to medicine has remained the conventional approach to the development of treatment drugs, the last few decades has seen a gradual shift towards the use of a combination of therapies that include the use of multiple components (Zhou et al, 2016). Recent research (Zhang et al 2011, Zhang et al 2014) has demonstrated that a combination of therapies can provide better therapeutic benefits to diseases such as diabetes, AIDS and cancer, all which have complex pathophysiology and aetiology and are therefore difficult to treat a single drug single target approach. As such, scientists in the field of medicine have made significant progress in the study of these synergistic effects of drugs. In this review, Lyon et al (2001) found mounting evidence to justify the use of Ginko biloba in combination with gingseng extract as a brain function enhancement intervention. They also fund that because of their diverse functional mechanisms, a combination of Ginko biloba and gingseng extract can have a significant benefit on ADHD management.

The quality and composition of interventions

The four studies used varied dosages of Ginko biloba. Two studies (Shakibaei et al 2015 and Salehi et al 2010) with the highest dosage of Ginko biloba (80e120 mg/day) reported a higher effectiveness of the extract intreating ADHD. However, even the other two studies that showed the lowest dosage of Ginko biloba showed a significant level of effectiveness and efficacy as a treatment intervention for ADHD. In Uebel-von Sandersleben et al (2014), participants received Ginko biloba EGb 761 tablets in a period of 3 to 5 weeks. The EGb 761 is a dry extract from Ginko biloba leaves in the form of an extraction solvent called acetone 60% (w/w). The acetone extraction was adjusted 22.0-27.0% of ginko flavonoids quantified as 5.0-7% terpenelactones consisting of 2.8-3.4 ginkgolides A,B,C and 2.6 -3.2% bilobalide containing less than 5ppm of ginkgolicacid. The intervention group received an initial dosage of 40mg twice a day and subsequently increased to 60 and 120 mg twice daily depending on the tolerability and efficiency on a weekly study visits. This is within the recommendations by Unger (2013) of 80mg -160mg of the EGb 761 leaf extract taken three times per day for at least 4 weeks. On the other hand, participants in Shakibaei et al (2015) received enteric coated tablets of Ginko biloba that has a total dosage of 80mg/day for those with less than 30kg body weight. The dosage was however gradually increased to 120mg per day for those with more than 30kg of weight. As per Unger (2013), the enteric coated tablet is an easy way of ensuring an easier oral administration of medicine. Nonetheless, like Uebel-von Sandersleben et al (2014), Shakibaei et al (2015) relied on extracts of Ginko biloba leaves standardized by a flavonoid glycoside 24% and terpene lactone 6%. However, while Uebel-von Sandersleben et al (2014) did not identify the solvent used in extraction, Ginko2 highlighted the use of water and ethanol as their extraction solvents. The participants in Salehi et al (2010) received tablets of Ginko T.D with a dosage of 80-120mg per day based on the subjects’ weights. Those with less than 30kg of weight received 80mg per day while those with more than more than 30kg of weight received 120mg per day for the intervention group. In the study by Salehi et al (2010), each tablet of Ginko TD contained 40mg of dried G.biloba extract- titrated up during the trial based on a predetermined schedule namely, week 1: 40mg per day while in week 2, 80mg per day. In week 3, the titration entailed 120mg per day for children with a weight of more than 30kgs delivered in bits of one capsule in the morning, one at midday and one at 4pm. Observably, both Shakibaei et al (2015) and Salehi (2010) used the same dosages of Ginko Biloba, except that the studies had different research designs that led to different findings. For instance, Shakibaei et al’s (2015) study was a randomized, double blinded, placebo controlled study, which compared the effectiveness of ginko biloba for ADHD only, while the stud by Salehi (2010) was a randomized, double blind, parallel group comparison study, which involved two groups of participants testing the difference in the effectiveness of two drugs: Ginko biloba extracts (Ginko T.D.™) and methylphenidate. The two different research designs taken by the two studies justify why whereas Shakibaei et al (2015) found results pertaining to only Ginko Biloba as an effective complementary treatment for ADHD, Salehi (2010) found that Ginko biloba was less effective than methylphenidate in the treatment of ADHD. In Lyon et al., (2001) the researchers distributed labelled bottles of 60 capsules of the AD-FX product. Each capsule contained 200mg of panax quinquefolium (ginseng extracts) and 50mg of Ginko biloba extract. The parents were instructed to give their children one capsule twice per day. Giseng extracts have traditionally been taken for various medicinal purposes, even though there has been no conclusive evidence on their effectiveness (Sierpina et al, 2003). Nonetheless, research by Sierpina et al (2003) associated giseng extracts with an improvement of cognition and thinking processes, quality of life and behaviour. However, studies conducted by Kim et al (2002) did not find any conclusive evidence for the effectiveness of giseng extracts for improved cognition.

Active constituent

Active consituents in GINGKO

HOW THEY WORK

FOR JM TO DO

Varitations of G.bilob

Refencing from the 4 trials discuss

The preparations of herbs and the formulations used

Implications for practice

The results of the present review indicate that Ginko biloba extracts can be used as a treatment alternative for ADHD for children. Uebel-von Sandersleben et al’s 2014 short term pilot study recommended that a 60 to 120 mg twice daily dosage of Ginko biloba extracts as an alternative for patients who do not intend to use methylphenidate. While the reviewed studies did not give a clear illustration of the mechanism in which Ginko biloba improves ADHD symptoms, evidence by Shakibaei et al 2015 show that Ginko biloba is a safe and effective complementary therapy for the treatment of children with ADHD. However, the fact that Salehi et al 2010 did not outrightly support the use of Ginko biloba in the treatment of ADHD raises the concern that perhaps further studies should be conducted on the same to ascertain existing evidence of effectiveness sand efficacy. Nonetheless, Lyon et al 2001 suggested that a combination of Panax quinquefolium and Ginkgo biloba can be used by practitioners to manage cognitive and behavioral difficulties presenting in children with ADHD.

Safety

Studies reviewed in this report reveal that when taken in recommended dosage, Ginko biloba extracts are safe for use as a means of treating ADHD in children. However, both patients and practitioners should be aware of reported side effects such as weakness, vomiting, nausea, and restlessness, especially when taken in large doses.

Conclusion and recommendations

The main aim of this critical review study was to identify evidence on the effectiveness of Ginko biloba as a treatment intervention for ADHD in children.

PROMISING IN NEUROLOGICAL CONDITIONS

CONSITUENTS OF GINGKO BILOBA

Trials indicated

Despite the inconclusive evidence by one of the reviewed studies in this report regarding the effectiveness and efficacy of Ginko biloba as a treatment intervention for children with ADHD, there is a general consensus among the three other studies that Ginko biloba extracts has beneficial effects on ADHD symptoms and can be used as an alternative treatment. These findings explain what appears to be an increasing popularity of standardized Ginko biloba leaf extract products. However, the presence of various adverse effects confirms the need for further research to ascertain the safety of Ginko biloba, especially for certain populations such as pregnant and breast-feeding mothers. But there are certain limitations to the reviewed studies that were identified by the respective authors. For instance, Uebel-von Sandersleben et al (2014) acknowledged that their study’s ipen pilot trial research design had several limitations to the study findings. For instance, the study admitted a small sample size with missing randomization and placebo control group. Similarly, Uebel-von Sandersleben et al (2014) did not have any blinding, neither did they have any reports from the teachers. More unfortunately, the study’s observational period was rather short. A smaller sample size specifically affects the generalizability of the study findings while the smaller observational period and lack of blinding affects the validity of the study findings. On the other hand, Shakibaei et al (2015) and Salehi et al (2010) did not have a pure placebo control wing of the study, the former due to the ethical limitation that methylphenidate, was already available for treatment of ADHD. Nonetheless, like, Uebel-von Sandersleben et al (2014), Shakibaei et al (2015) acknowledged that the shorter observation period may have affected the validity of their findings. Lastly, Lyon et al (2001) acknowledged a limitation with their repeated use of CPRS-R(L) diagnostic tool, which has a potential for some placebo effects. Moreover, there are certain limitations of this critical review that are worth noting. For instance, the review relied on only four studies for the review, affecting the quality of findings in the sense that only a small sample size and low number of effects are evaluated.

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