Clonidine Extended-Release Tablets for Pediatric Patients With Attention-Deficit/Hyperactivity Disorder

R/D Clinical Research Inc., 461 This Way, Lake Jackson, TX 77566, USA.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 02/2011; 50(2):171-9. DOI: 10.1016/j.jaac.2010.11.005
Source: PubMed


This study examined the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
This 8-week, placebo-controlled, fixed-dose trial, including 3 weeks of dose escalation, of patients 6 to 17 years old with ADHD evaluated the efficacy and safety of CLON-XR 0.2 mg/day or CLON-XR 0.4 mg/day versus placebo in three separate treatment arms. Primary endpoint was mean change in ADHD Rating Scale-IV (ADHD-RS-IV) total score from baseline to week 5 versus placebo using a last observation carried forward method. Secondary endpoints were improvement in ADHD-RS-IV inattention and hyperactivity/impulsivity subscales, Conners Parent Rating Scale-Revised: Long Form, Clinical Global Impression of Severity, Clinical Global Impression of Improvement, and Parent Global Assessment from baseline to week 5.
Patients (N = 236) were randomized to receive placebo (n = 78), CLON-XR 0.2 mg/day (n = 78), or CLON-XR 0.4 mg/day (n = 80). Improvement from baseline in ADHD-RS-IV total score was significantly greater in both CLON-XR groups versus placebo at week 5. A significant improvement in ADHD-RS-IV total score occurred between groups as soon as week 2 and was maintained throughout the treatment period. In addition, improvement in ADHD-RS-IV inattention and hyperactivity/impulsivity subscales, Conners Parent Rating Scale-Revised: Long Form, Clinical Global Impression of Improvement, Clinical Global Impression of Severity, and Parent Global Assessment, occurred in both treatment groups versus placebo. The most common treatment-emergent adverse event was mild-to-moderate somnolence. Changes on electrocardiogram were minor and reflected the known pharmacology of clonidine.
Clonidine hydrochloride extended-release tablets were generally well tolerated by patients in the study and significantly improved ADHD symptoms in this pediatric population.

31 Reads
  • Source
    • "Data generated during the development of the forthcoming DSM-V may shed further light on the validity and utility of the current subtype classification. Finally, the 30% attrition rate observed across GXR and placebo groups in the current report is within the range of dropout rates observed for a similar short-term study of extended-release clonidine for treating ADHD in children and adolescents ( Jain et al. 2011), and is also consistent with some trials of amphetamine for treating adult ADHD (Castells et al. 2011). As has been discussed with regard to studies of psychostimulant treatments for ADHD, this dropout rate may indicate that some patients did not tolerate the intervention. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness. Data from two large double-blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were analyzed. Using the pooled population to provide sufficient sample size and associated statistical power, the impact of GXR treatment on core ADHD symptoms was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the overall GXR and placebo groups in subjects with each of the three ADHD subtypes. ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the overall study population by randomized dose group (vs. placebo) were also examined. The full analysis set included 631 subjects aged 6-17 years (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive subtype of ADHD, differences in least squares (LS) mean reductions from baseline in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5 and end point (p≤0.020). Among subjects with combined type ADHD, differences in LS mean ADHD-RS-IV total score reductions from baseline were significantly greater in the GXR group (n=354) than in the placebo group (n=100) at treatment weeks 1 through 5 and end point (p≤0.011). The dearth of predominantly hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup. Each randomized GXR dose group in each trial demonstrated significantly greater reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores than did the respective placebo group at end point (p≤0.05 for all). The results support the use of GXR in the treatment of core ADHD symptoms as defined in the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision, including hyperactivity, impulsivity, and inattention.
    Journal of child and adolescent psychopharmacology 05/2012; 22(3):206-14. DOI:10.1089/cap.2010.0135 · 2.93 Impact Factor
  • Source
    • "Alpha-2 agonists (clonidine and guanfacine), which decrease the firing of noradrenaline neurons in locus ceruleus (Scahill 2009), can offer a combined improvement in both tic and ADHD symptoms (Bloch et al. 2009). Clonidine can be effective in both children with TD (Du et al. 2008; Hedderick et al. 2009) and ADHD ( Jain et al. 2011), with possible improvements in hyperactivity, impulsiveness , and inattention in children with tic disorders. Also guanfacine significantly improves ADHD symptoms in children with tic disorders (Scahill et al. 2001). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tourette's disorder (TD) in children and adolescents is frequently co-morbid with attention-deficit/hyperactivity disorder (ADHD). Dopamine-blockers are the first line treatment for TD, whereas dopamine-agonists, such as stimulants, are the gold-standard in the treatment of ADHD. These contrasting effects supported concerns about the risk that stimulants for treating ADHD may trigger or worsen co-morbid tics. Aripiprazole, a partial dopamine agonist, acts as an antagonist at dopamine D2 receptors in hyperdopaminergic conditions and displays agonist properties under hypodopaminergic conditions. The present study describes the use of aripiprazole (10.0 ± 4.8 mg/day) in a consecutive group of 28 patients with a primary diagnosis of TD and co-morbid ADHD, combined subtype. The Yale Global Tic Severity Scale (YGTSS) and the ADHD-Rating Scale (ADHD-RS-IV) were used as primary outcome measures and both significantly improved (p<0.001) after the treatment. Global measures of severity (Clinical Global Impressions-Severity) and of functional impairment (Children's Global Assessment Scale) also significantly improved during the treatment (p<0.001). At the YGTSS there was a reduction of 42.5%, in motor tics, of 47.9% in phonic tics (44.7% for the combined scores), and of 32.3% in tic impairment. Nineteen patients (67.9%) had a reduction of at least 50% of the YGTSS score (motor+phonic tics). The improvement at the ADHD-RS-IV score was 22.5%, 12 patients (42.8%) presented an improvement of 30%, but only 2 (7.1%) an improvement greater than 50%. Using a logistic regression model, a reduction of at least 30% in ADHD-RS-IV score was more likely to occur in the obsessive-compulsive disorder co-morbid group. Aripiprazole was well tolerated and none of the patients discontinued medication because of side effects. In summary, aripiprazole resulted in an effective treatment for TD, but it was only moderately effective on co-occurring ADHD symptomatology. Our preliminary data suggest that aripiprazole may represent a possible therapeutic option, among other possible monotherapies addressing both tics and ADHD.
    Journal of child and adolescent psychopharmacology 02/2012; 22(2):120-5. DOI:10.1089/cap.2011.0081 · 2.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clonidine has been used off-label in children and adolescents with attention deficit and hyperactivity disorders (ADHD) with or without comorbidities. Clonidine extended-release was recently approved by the US Food and Drug Administration for ADHD in children. This review evaluates the efficacy and safety of clonidine extended-release and clonidine in children and adolescents with ADHD. A search of the Medline database and clinical trials register from 1996-2011 yielded ten clinical trials for critical evaluation of efficacy and safety. Eight of the ten trials reviewed were double-blinded and placebo-controlled. Nine of the ten trials utilized multiple outcome measures. Both clonidine extended-release and clonidine, as monotherapy or adjunctive therapy, were reported to be efficacious in treating ADHD symptoms in children and adolescents with or without comorbid disorders in nine of the ten clinical trials. One study showed clonidine to be ineffective in improving performance of a single task, at a specific point in time, in a small number of subjects. All of the studies that evaluated safety reported clonidine and clonidine extended-release to be well tolerated. The side effects of clonidine included somnolence, fatigue, headache, bradycardia, hypotension, and clinically insignificant electrocardiographic changes. However, there are historical anecdotal reports of serious cardiac side effects, including death in cases with other risk factors. None of the studies compared clonidine extended-release with clonidine in subjects with ADHD. Therefore, it is not clear whether clonidine extended-release is advantageous over clonidine, with regard to either efficacy or safety. It is equally unclear whether clonidine or clonidine extended-release is more efficacious in treating ADHD in subjects with comorbid disorders than in those without comorbidities. All the studies reviewed had limitations in their designs and methods. Clonidine and clonidine extended-release could be efficacious and safe for the treatment of ADHD both as monotherapy and as adjunctive therapy with stimulant medications in selected patients. There is a need for clinical trials to determine the long-term efficacy and safety of treatment with clonidine and clonidine extended-release in patients with ADHD.
    Adolescent Health, Medicine and Therapeutics 09/2011; 2:105-112. DOI:10.2147/AHMT.S15672
Show more