Immediate-Release Versus Extended-Release Guanfacine for Treatment of Attention-Deficit/Hyperactivity Disorder
Published Online: August 15, 2013
Vanja Sikirica, PharmD, MPH; Jipan Xie, MD, PhD; Tony Lizhang He, BS; M. Haim Erder, PhD; Paul Hodgkins, PhD, MSc; Hongbo Yang, PhD; Thomas Samuelson, BA; and Eric Q. Wu, PhD
Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed pediatric psychiatric disorder in the United States, affecting about 7.2% of children and adolescents.1 The core symptoms of ADHD include hyperactivity, impulsivity, and inattention.2 If untreated, ADHD can delay social and academic development, with symptoms and dysfunction persisting into adulthood in approximately 70% of patients.3-5 In addition, children and adolescents with ADHD are likely to have mental health comorbidities.2 Attention-defi cit/hyperactivity disorder poses a substantial economic burden, with estimated annual societal costs of $143 to $266 billion (2010 dollars) in the United States.6 Furthermore, ADHD patients incur excess costs from treating mental health comorbidities that are commonly associated with ADHD.7
According to guidelines from the American Academy of Pediatrics, a school-aged child or adolescent diagnosed with ADHD should be treated with behavioral therapy and/or a stimulant as the fi rst-line medication.8 Although stimulants are the most frequently prescribed medications for ADHD up to 30% of patients using stimulants are intolerant to treatment or have an inadequate response.9 For these patients, a nonstimulant medication may be used.9 Nonstimulants approved by the US Food and Drug Administration (FDA) for ADHD treatment include atomoxetine, clonidine extended release, and guanfacine extended release (GXR).10
Guanfacine is a centrally acting slective alpha-2A adrenoceptor agonist that has been shown to improve prefrontal cortex neuronal firing and strengthen working memory in primates.11 This pharmacologic action is the basis for treating human prefrontal cortex–related cognitive disorders.11 Guanfacine extended release is used as monotherapy or adjunctive therapy to stimulants for ADHD treatment in children and adolescents.12 It appears to be more efficacious than atomoxetine, a commonly used nonstimulant, at the target dose in indirect comparison studies.13,14
Guanfacine is also marketed in an immediate-release formulation in the United States. Guanfacine immediate release (GIR) was approved by the FDA in 1986 for hypertension treatment only.15 However, its off-label use to treat psychiatric disorders, including ADHD, is common.11,16 Although GIR has the same active moiety as GXR, there is limited clinical evidence supporting GIR use in the treatment of ADHD. Only 1 small (n = 34) placebo-controlled trial has been conducted to evaluate GIR’s efficacy and safety in children with concomitant tic disorders and ADHD.15,17
The 2 formulations of guanfacine have distinct pharmacokinetic profi les and dosing requirements.15 While GIR is metabolized quickly in children,11,16,18 GXR is synthesized with rate-controlling polymers and organic acids that lead to a prolonged half-life.19 Despite differences between GIR and GXR, payers and other decision makers (parents/caregivers) may treat the 2 drugs equally. Some payers who reimburse GXR may require a step-edit with GIR or a prior authorization prior to use of GXR.20,21 This policy assumes that GIR and GXR are reasonable substitutes in ADHD treatment, but this assumption needs to be tested in terms of efficacy, tolerability profiles, usage patterns, and economic outcomes.
To date, no study has directly compared the impact of GIR use versus GXR use among ADHD patients. To better understand the real-world differences between the 2 drugs with respect to their impact on patients, this retrospective cohort study compared the treatment patterns, resource utilization, and healthcare costs associated with GIR therapy versus GXR therapy in patients with ADHD.
Data were extracted from the Truven Health MarketScan Commercial Claims & Encounters database for the period of 2009 to 2010. The database contains de-identified enrollment data and inpatient and outpatient medical and outpatient pharmacy claims from large employers and health plans across the United States.
The study sample consisted of ADHD patients who initiated therapy with GIR or GXR from November 2009 to December 2010 (GXR was launched in November 2009). The first fill of either drug during this period was defi ned as the index drug, and the date of the fill was defi ned as the index date. The 6 months before and the 6 months after the index date were defi ned as thepreindex period and the study period, respectively. Patients were further required to meet the following criteria: (1) to have at least 1 primary diagnosis of ADHD, identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 314.00 and 314.01, during the preindex period; (2) to be aged 6 to 17 years as of the index date; and (3) to have continuous eligibility during the preindex and study periods. Patients were excluded if they used GIR or GXR during the preindex period or were diagnosed with hypertension (ICD-9-CM codes 401.xx, 459.3x, 642.3x, 643.3x, and 997.91) during the preindex or study periods. Patients were allowed to take other ADHD medications during the preindex period.
Outcomes categories measured during the 6-month study period included treatment patterns, resource utilization, and healthcare costs.
Treatment Patterns. Treatment patterns included medication possession ratio (MPR), daily average consumption (DACON), discontinuation, switching, and augmentation. Defi nitions of treatment patterns used in this study are in concordance with International Society for Pharmacoeconomics and Outcomes Research guidelines22 and have been used previously.23,24 Medication possession ratio, defi ned as the total number of days of drug supply divided by the total number of days in the study period (ie, 6 months), was used to measure adherence to the index drug. Daily average consumption was defi ned as the quantity of pills supplied during the study period divided by total number of days supplied within the study period.
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