Ginkgo biloba for Attention-Deficit/Hyperactivity Disorder in children and adolescents: A double blind, randomized controlled trial

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Abstract

Background

Although stimulants are highly effective in controlling the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), some children will not respond to, or are intolerant of stimulants. Thus, the desire for safe and effective nonstimulant medications has risen during the past several years. Ginkgo biloba has been suggested in the treatment of dementia and memory impairment. We hypothesized that G. biloba would be beneficial for treatment of ADHD, and this could be evaluated in a double blind, randomized, parallel group comparison of G. biloba (Ginko T.D.™ Tolidaru, Iran) and methylphenidate.

Methods

Fifty outpatients (39 boys and 11 girls) with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of Ginko T.D.™ at a dose of 80–120 mg/day depending on weight (80 mg/day for < 30 kg and 120 mg/day for > 30 kg) (group 1) or methylphenidate at a dose of 20–30 mg/day depending on weight (20 mg/day for < 30 kg and 30 mg/day for > 30 kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale- IV. Patients were assessed at baseline and at 21 and 42 days after the medication started.

Results

Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: − 6.52 ± 11.43 (mean ± S.D.) and − 15.92 ± 11.44 (mean ± S.D.) for Ginko T.D.™ and methyphenidate, respectively for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: − 0.84 ± 6.79 (mean ± S.D.) and − 14.04 ± 8.67 (mean ± S.D.) for Ginko T.D.™ and methyphenidate, respectively for Teacher ADHD Rating Scale.

The difference between the Ginko T.D.™ and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group.

Conclusion

The results of this study suggest that administration of G. biloba was less effective than methylphenidate in the treatment of ADHD.

Introduction

Attention-deficit hyperactivity disorder (ADHD) is the most common neurobehavioural disorder of childhood. The incidence of ADHD is 5–10% in children and the symptoms are known to persist into adulthood in 10–60% of cases (Mohammadi and Akhondzadeh, 2007). Psychostimulant medications continue to be a primary treatment modality for children with ADHD (Cormier, 2008, Dopheide and Pliszka, 2009). Although the etiology of ADHD is not fully understood, potent drugs are being employed for its medical management while safe and effective alternatives are being neglected (Noorbala and Akhondzadeh, 2006, Mohammadi and Akhondzadeh, 2007, Cormier, 2008, Dopheide and Pliszka, 2009). Neurochemical studies suggest alterations in catecholaminergic — mainly dopaminergic and noradrenergic-transmitter functions markedly contribute to the symptoms of ADHD (Cormier, 2008). The symptoms of ADHD are significantly ameliorated by agents that specifically influence these neurotransmitter systems (Curatolo et al., 2009). Approximately 70% of the children treated with stimulants show improvement in the primary ADHD symptoms and in co-morbidity such as conduct disorder, although the benefits may not hold beyond two years (Noorbala and Akhondzadeh, 2006). Despite the well-established efficacy and safety of stimulants for ADHD, alternative medicines are still needed for several reasons (Richard et al., 2003). About 30% of children and adolescents with ADHD may not respond to stimulants or may be unable to tolerate potential adverse events such as decreased appetite, mood lability and sleep disturbances (Mohammadi and Akhondzadeh, 2007). Although stimulants do not increase risk for later substance abuse in ADHD, concerns have been raised about special prescription rules, and a potential for abuse by persons other than the ADHD subjects (Mohammadi and Akhondzadeh, 2007). Herbal medicines have been shown to ameliorate ADHD related behaviors (Akhondzadeh et al., 2005). For example, a recent study showed that Passiflora incarnata may be a novel therapeutic agent for the treatment of attention deficit hyperactivity disorder. In addition, a tolerable side effect profile may be considered as one of the advantages of Passiflora in the treatment of attention deficit hyperactivity disorder (Akhondzadeh et al., 2005). Ginkgo biloba has been suggested in the treatment of dementia and memory impairment (Canter and Ernst, 2007, Birks and Grimley Evans, 2009). Nevertheless, a recent systematic review has concluded that there is no convincing evidence that G. biloba has a positive effect on any aspect of cognitive performance in healthy people (Canter and Ernst, 2007). In addition, some studies suggest G. biloba in the treatment of ADHD, especially in children who are primarily inattentive (Lyon et al., 2001, Frei, 2002). Ginkgo improves cerebrovascular blood flow and may help to reduce hyperactivity due to boredom and lack of focus (Lyon et al., 2001, Ponto and Schultz, 2003). Ginkgo extract has been shown to affect several central neurotransmitter systems (Nathan, 2000); it has been shown to reverse the reduction in 5-HT1A receptors and noradrenergic receptors in the aged rat (Huguet and Tarrade, 1992, Winter and Timineri, 1999). It was demonstrated that ginkgo extract produces reversible inhibition of both MAO-A and MAO-B in the brain (White et al., 1996). This mechanism may underlie the anxiolytic and mild antidepressant effects of ginkgo extract, and it may contribute to the improvement in the symptoms of ADHD (Ponto and Schultz, 2003). The action of G. biloba was investigated in 50 hyperactive children aged from 2 to 13 years. It was found that G. biloba had a greater effect on excitability, frustration tolerance and mood than methylphenidate (Lyon et al., 2001). Although many medicinal plants textbooks refer to efficacy of G. biloba in the treatment of ADHD, there is no enough evidence-based documents so far (Akhondzadeh, 2007). In addition, the Lyon study was an open label trial (Lyon et al., 2001). Therefore, we hypothesized that G. biloba would be beneficial for treatment of ADHD, and this could be evaluated in a double blind, randomized, parallel group comparison of G. biloba (Ginko T.D.™ Tolidaru, Iran) and methylphenidate.

Section snippets

Trial setting

This was a six-week, parallel group, randomized clinical trial undertaken in an outpatient child and adolescent clinic at Roozbeh Psychiatric Hospital in Tehran, Iran during April 2007–May 2009.

Participants

Male and female subjects, ages 6 to 14 years included 50 outpatients (39 boys and 11 girls) with a DSM-IV-TR diagnosis of ADHD were study population of this trial. At screening, investigators conducted a psychiatric evaluation with the DSM-IV-TR criteria for ADHD and the Kiddie Schedule for Affective

Results

No significant differences were identified between patients randomly assigned to the Group 1 or 2 conditions with regard to basic demographic data including age, gender and ethnicity (Table 1).

Discussion

Stimulant pharmacotherapy has been used for many decades in the treatment of ADHD, in conjunction with psychosocial interventions such as parent training, contingency management, and social skills training (Mohammadi and Akhondzadeh, 2007). Although stimulants are highly effective in controlling the symptoms of ADHD, some children will not respond to, or are intolerant of stimulants. Thus, the desire for safe and effective nonstimulant medications has risen during the past several years (

Acknowledgments

This study was Dr. Reza Imani's thesis toward the Iranian board of child psychiatry. This study was supported by a grant (grant number: 5404) from Tehran University of Medical Sciences to Prof. Shahin Akhondzadeh.

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