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


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.


CONCLUSIONS
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.
Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan ; Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Tsuyoshi
T
Sasaki
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
Kenji
K
Hashimoto
Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan.
Masumi
M
Tachibana
Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan.
Tsutomu
T
Kurata
Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan.
Keiko
K
Okawada
Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan.
Maki
M
Ishikawa
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Hiroshi
H
Kimura
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Hideki
H
Komatsu
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Masatomo
M
Ishikawa
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Tadashi
T
Hasegawa
Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan.
Akihiro
A
Shiina
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Tasuku
T
Hashimoto
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
Nobuhisa
N
Kanahara
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Tetsuya
T
Shiraishi
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.
Masaomi
M
Iyo
GIRK channel; antitussive; attention deficit/hyperactivity disorder; nucleus accumbens; pediatric; tipepidine