Effects of Adding Tizanidine on Stimulants in Treatment of ADHD: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background: Attention deficit hyperactivity disorder (ADHD) is defined as a neurodevelopmental disorder and is one of the most common psychiatric disorders in children and adolescents. Various treatments have been recommended to manage this disorder, including stimulants and non-stimulants. Stimulants are the first-line treatment strategy for ADHD; however, approximately 30 of patients exhibit drug resistance or sensitivity to these medications. Consequently, other drug groups, such as Alpha2 agonists, are used in such cases. Clonidine and guanfacine are Food and Drug Administration (FDA)-approved drugs for the treatment of ADHD, and they belong to this group. Tizanidine is an Alpha2 agonist that has not yet been studied for this disorder. Objectives: Due to the lack of information and studies in this area, the purpose of this study is to investigate the effects of adding tizanidine to stimulants in the treatment of ADHD. Methods: This research was a double-blind, placebo-controlled, randomized trial conducted in outpatient units and admission wards of university hospitals. Forty patients aged 6 to 18 years, with at least one month of unsuccessful treatment of ADHD with lisdexamfetamine (Vyvanse), participated in the study. The participants received either Vyvanse and tizanidine (group 1, n = 20) or Vyvanse alone (group 2, n = 19) for an 8-week period. Symptom severity improvement was assessed using the CONNERS' Parent Rating Scale-48 (CPRS-48) and the Swanson, Nolan, and Pelham Rating Scale (SNAP-IV). Safety measurements were assessed using pulse rate, blood pressure, and electrocardiogram (ECG) changes during the study period. Results: During the 8-week follow-up, SNAP-IV measures did not change significantly in either of the two groups. A significant within-group change was observed only in the conduct domain of CPRS-48 (P < 0.05). Conclusions: Adding tizanidine is not effective in the treatment of ADHD but demonstrates sufficient safety for use in the pediatric age group. © 2025, Karbasi Amel et al.