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

Abstract

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...

Efficacy and safety of tipepidine as adjunctive therapy in major depressive disorder: A randomized, double‐blind, placebo‐controlled clinical trial

“…In addition to depression, tipepidine has shown beneficial therapeutic effects in other psychiatric disorders involving the dopaminergic system. In this regard, in a recent randomized, double‐blind clinical trial, we demonstrated that add‐on treatment with methylphenidate and tipepidine improved hyperactivity‐impulsivity of attention deficit hyperactivity disorder 56 . The findings of the current study are in agreement with previous clinical findings, showing that adjunctive treatment with citalopram and tipepidine significantly improves severity of depression in patients with MDD.…”

Using the drug repositioning approach to develop a novel therapy, tipepidine hibenzate sustained-release tablet (TS-141), for children and adolescents with Attention-Deficit/Hyperactivity Disorder

“…These trials have reported its efficacy in pediatric patients with ADHD at the same dose as the original indication of antitussives (30 mg/day). In a recently reported Iranian placebo-controlled study, in which tipepidine is added to methylphenidate, its effect on ADHD was confirmed at the same dose as antitussives, although the study design was different from that of the TS-141 phase II study [29].…”

Using the drug repositioning approach to develop a novel therapy, tipepidine hibenzate sustained-release tablet (TS-141), for children and adolescents with attention-deficit/hyperactivity disorder

“…These trials have reported its efficacy in pediatric patients with ADHD at the same dose as the original indication of antitussives (30 mg/day). In a recently reported Iranian placebo-controlled study, in which tipepidine is added to methylphenidate, its effect on ADHD was confirmed at the same dose as antitussives, although the study design was different from that of the TS-141 phase II study [ 29 ]. Conversely, the upper dose was set to 120 mg, the maximum dose of Asverin to reduce the clinical data package for application using the abundant safety profile of Asverin.…”