Tipepidine in adolescent patients with depression: a 4 week, open-label, preliminary study

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

doi:10.2147/ndt.s63075

Cited by 15 publications

(10 citation statements)

References 26 publications

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“…Beyond the common usage of tipepidine, this agent is nowadays considered for its neuropsychiatric characteristics as well. A large body of evidence has shown that tipepidine can play a therapeutic role in a variety of neuropsychological disorders such as depression and obsessive–compulsive disorder (OCD) . Additionally, an efficient and safe role for tipepidine in the treatment of ADHD and its characteristic symptoms has also been suggested .…”

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confidence: 99%

Efficacy and safety of tipepidine as adjunctive therapy in children with attention‐deficit/hyperactivity disorder: Randomized, double‐blind, placebo‐controlled clinical trial

Dehbozorghi

Bagheri

Moradi

et al. 2019

Psychiatry Clin Neurosci

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Aim: This study evaluated the efficacy and safety of tipepidine as an add-on to methylphenidate in the drug treatment of attention-deficit/hyperactivity disorder (ADHD).Methods: This study was an 8-week, randomized, parallel group, double-blind, placebo-controlled trial recruiting 53 ADHD-diagnosed children. Patients were randomly divided to receive methylphenidate + tipepidine or methylphenidate + placebo for 8 weeks. Participants were assessed using the parent version of ADHD Rating Scale-IV and the Clinical Global Impression scale at baseline, at week 4, and at the end of the trial. Moreover, the safety and tolerability of the treatment strategies were compared.Results: On general linear model repeated measures analysis a significant effect was seen for time × treatment interaction on the total and hyperactivity-impulsivity subscales of the Parent ADHD Rating Scale-IV during the trial period (Greenhouse-Geisser corrected: F = 3.45, d.f. = 1.52, P = 0.049, and F = 5.17, d.f. = 1.52, P = 0.014, respectively). The effect for time × treatment interaction, however, was not significant on Clinical Global Impression-Severity scale (Greenhouse-Geisser corrected: F = 1.79, d.f. = 1.43, P = 0.182). The frequencies of adverse events were similar between the two groups.Conclusion: Eight weeks of treatment with tipepidine, as a supplementary medication, resulted in satisfactory efficacy and safety of the adjuvant therapy in management of patients with ADHD. Rigorous investigations, however, involving larger sample sizes, more extended treatment periods, and dose responses should be considered.Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders, affecting 3-7% of school-age children. It is delineated by inattentiveness symptoms, impulsive behavior, and hyperactivity in cases lasting for at least 6 months. 1 ADHD patients may have to deal with many challenges due to their unusual characteristics, which persist into adulthood in approximately 60%-80% of cases. 2 In general, patients with ADHD are susceptible to having slower rates of processing, lower self-esteem, increased risk of motor vehicle accidents, sexual and socially related problems, and psychiatric comorbidity. [3][4][5] Attention-deficit/hyperactivity disorder could occur due to imbalance of catecholamine metabolism in the cerebral cortex, and the impaired dopaminergic and noradrenergic function of several areas such as the prefrontal cortex (PFC). 6 Treatment for ADHD consists of behavioral therapy, drug therapy, or a combination of both; the two latter approaches seem to have the most effect. 7-9 Accordingly, the standard treatment for all groups of ADHD currently is focused on modification of the imbalance, using either stimulants or non-stimulants. Among the studied psychostimulants, methylphenidate (Ritalin) is the most extensively used medication, which leads to higher concentrations of synaptic dopamine by inhibiting the dopamine transporter. 10 Ordinarily, stimulants are safe and extremely effective; nonethele...

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confidence: 99%

Efficacy and safety of tipepidine as adjunctive therapy in children with attention‐deficit/hyperactivity disorder: Randomized, double‐blind, placebo‐controlled clinical trial

Dehbozorghi

Bagheri

Moradi

et al. 2019

Psychiatry Clin Neurosci

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“…Interestingly, this drug appears to have novel antidepressant-like effects that may be mediated through activation of mesolimbic dopamine neurons through GIRK channel inhibition (Hamao et al, 2015;Hamasaki et al, 2013;Kawahara et al, 2013). Two pilot studies suggest that tipepidine may improve adolescent depression and ADHD (Sasaki, Hashimoto, Tachibana, Kurata, Kimura, et al, 2014;Sasaki, Hashimoto, Tachibana, Kurata, Okawada, et al, 2014). These studies point to GIRK channels as an additional therapeutic target in depression and behavior.…”

Section: Girk Channel Drug Interactionsmentioning

confidence: 99%

Structural Insights into GIRK Channel Function

Glaaser

Slesinger

2015

International Review of Neurobiology

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“…Tipepidine, which inhibits GIRK channel activity, is used clinically as a nonnarcotic antitussive and was recently evaluated for its ability to improve ADHD symptoms in pediatric patients. A preliminary pilot study indicated that tipepidine was well tolerated and improved ADHD rating scale scores (Sasaki et al, 2014). This suggests that inhibition of GIRK-dependent signaling might offer treatment options for ADHD that are safer than the current use of psychostimulants, which have undesirable side effects.…”

Section: Girk Channels In Cns Disordersmentioning

confidence: 99%

“…Preliminary results indicate that the GIRK channel inhibitor tipepidine may be effective in treating ADHD in children (Sasaki, Hashimoto, Tachibana, Kurata, Okawada, et al, 2014), and preclinical and preliminary clinical studies suggest that it may have uses in other psychiatric disorders, such as anxiety and depression (Honda et al., 2011; Kawaura et al, 2012; Sasaki et al, 2014). In addition, new classes of potent, subunit-selective GIRK channel compounds have been identified that could enable pharmacological targeting of particular brain regions and behaviors.…”

Section: Therapeutic Potential Of Girk Channel Modulatorsmentioning

confidence: 99%

Behavioral and Genetic Evidence for GIRK Channels in the CNS

Mayfield

Blednov

Harris

2015

International Review of Neurobiology

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G protein-coupled inwardly rectifying potassium (GIRK) channels are widely expressed throughout the brain and mediate the inhibitory effects of many neurotransmitters. As a result, these channels are important for normal CNS function and have also been implicated in Down syndrome, Parkinson’s disease, psychiatric disorders, epilepsy, and drug addiction. Knockout mouse models have provided extensive insight into the significance of GIRK channels under these conditions. This review examines the behavioral and genetic evidence from animal models and genetic association studies in humans linking GIRK channels with CNS disorders. We further explore the possibility that subunit-selective modulators and other advanced research tools will be instrumental in establishing the role of individual GIRK subunits in drug addiction and other relevant CNS diseases and in potentially advancing treatment options for these disorders.

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Tipepidine in adolescent patients with depression: a 4 week, open-label, preliminary study

Cited by 15 publications

References 26 publications

Efficacy and safety of tipepidine as adjunctive therapy in children with attention‐deficit/hyperactivity disorder: Randomized, double‐blind, placebo‐controlled clinical trial

Efficacy and safety of tipepidine as adjunctive therapy in children with attention‐deficit/hyperactivity disorder: Randomized, double‐blind, placebo‐controlled clinical trial

Structural Insights into GIRK Channel Function

Behavioral and Genetic Evidence for GIRK Channels in the CNS

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