A mixed herbal extract as an adjunctive therapy for attention deficit hyperactivity disorder: A randomized placebo-controlled trial

Background: Methylphenidate improves clinical symptoms and brain activity in attention deficit hyperactivity disorder (ADHD) patients through the attention-regulation network's dopamine system. Additionally, water-soluble extracts (HX106) of four plants (Gastrodia elata Blume, Liriope platyphylla Wang et Tang, Salvia miltiorrhiza Bunge, and Dimocarpus longan Lour) improve cognitive function. We hypothesized that the combination of HX106 and methylphenidate would improve ADHD symptoms and brain activity of the attention network more effectively than the combination of placebo and methylphenidate. Methods: Twenty-seven patients with ADHD were administered a herbal mixture and methylphenidate (n=13), or placebo and methylphenidate (n=14) during a 4-week, randomized, double-blind, placebo-controlled clinical trial. Changes in ADHD symptoms (K-ARS scores), as well as brain activity and functional connectivity, were assessed at baseline and 4 weeks later. Results: The HX106 group showed a greater improvement in total attention (16.8%) and inattention (17.2%) scores than the placebo group. The HX106 group showed increased brain activity within the left precuneus compared to the placebo group. The HX106 group also showed increased functional connectivity from the precuneus seed to the left middle temporal gyrus compared with the placebo group. In all participants, the changes in K-ARS scores were negatively correlated with changes in brain activity in the left middle temporal gyrus. Conclusions: HX106 enhanced the effect of methylphenidate on ADHD symptoms and increased brain activity in the attention-regulation network. Therefore, HX106 may be an effective adjunctive therapy for patients with ADHD