Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

Tsuyoshi Sasaki; Kenji Hashimoto; Masumi Tachibana; Tsutomu Kurata; Keiko Okawada; Maki Ishikawa; Hiroshi Kimura; Hideki Komatsu; Masatomo Ishikawa; Tadashi Hasegawa; Akihiro Shiina; Tasuku Hashimoto; Nobuhisa Kanahara; Tetsuya Shiraishi; Masaomi Iyo

doi:10.2147/NDT.S58480

Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

Neuropsychiatr Dis Treat. 2014 Jan 24:10:147-51. doi: 10.2147/NDT.S58480. eCollection 2014.

Authors

Affiliations

¹ Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan ; Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
² Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
³ Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan.
⁴ Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
⁵ Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan ; Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan ; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.

Abstract

Background: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK)-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD) symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.

Subjects and methods: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0) received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS), Japanese version, and the Das-Naglieri Cognitive Assessment System (DN-CAS), Japanese version.

Results: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores) improved significantly (P<0.001). Furthermore, a comparison of baseline DN-CAS total scores and 4-week end-point scores showed a mild trend of improvement (P=0.093). Tipepidine was well tolerated, with no patients discontinuing medication because of side effects.

Conclusion: Our pilot study suggests that tipepidine therapy may prove to be an effective alternative treatment for pediatric patients with ADHD. Nonetheless, more detailed randomized, double-blind trials are needed to confirm tipepidine's efficacy.

Keywords: GIRK channel; antitussive; attention deficit/hyperactivity disorder; nucleus accumbens; pediatric; tipepidine.