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