Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders

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.

Treating insomnia with medications

“…Prazosin, a norepinephine antagonist, has demonstrated value in treating insomnia associated with PTSD nightmares (Raskind et al 2003). Clonidine is sometimes utilized to treat the agitation and insomnia that result from using amphetamines to treat AD/HD in pediatric patients (Ming et al 2011).…”

Actualización en el tratamiento farmacológico del trastorno por déficit de atención/hiperactividad: lisdexanfetamina y guanfacina de liberación retardada

“…También se ha comprobado la eficacia de la LDX en pacientes tratados previamente con MPH y cuya respuesta no fue adecuada, medida cuantitativamente -menos de un 30% de reducción en la ADHD Rating Scale (ADHD-RS)-, con una respuesta clínica adecuada en casi el 80% de los pacientes, que en numerosas ocasiones se acompañó de una mejoría en la manifestación de los sentimientos medida a través de la escala de expresión emocional para niños [22,23]. De igual forma, los diferentes trabajos han demostrado la alta seguridad del producto [7,13,15,19,[23][24][25][26][27][28][29][30][31][32][33][34].…”

“…Los incrementos conocidos de la frecuencia cardíaca tras la retirada de la GXR señalan la recomendación lógica de proceder a una retirada lenta en los casos que así se precise (por efectos adversos o ine ficacia). Aunque se han descrito unos 'supuestos casos aislados' (con una dudosa relación causa-efecto) de muerte súbita en pacientes tratados con clonidina y estimulantes, no se han comunicado casos similares con la GXR [31,32]. En caso de patología cardíaca conocida, antecedentes de muerte súbita o historia familiar o personal de un síndrome de QT largo, deberá realizarse una interconsulta a cardiología antes de comenzar el tratamiento.…”

Period Prevalence of Concomitant Psychotropic Medication Usage Among Children and Adolescents with Attention-Deficit/Hyperactivity Disorder During 2009

“…However, for a variety of reasons, including inadequate or partial response and dose-limiting side effects, there is evidence that some ADHD patients augment their existing stimulant regimen with additional medications (Pliszka 2003; Banaschewski et al 2004). Currently, the only therapies approved by the United States Food and Drug Administration (FDA) for adjunctive treatment of ADHD in children and adolescents are guanfacine extended release (XR) and clonidine XR (Ming et al 2011;Childress 2012). In practice, however, other medications are prescribed off label for the treatment of ADHD alongside stimulants, including antipsychotics, antidepressants, nonstimulants, and other stimulants (as adjunctive therapy) (Pappadopulos et al 2002;Spencer and Biederman 2002;Cooper et al 2004Cooper et al , 2006Zito et al 2008;Czaja and Valuck 2012).…”