Date Published: November 28, 2018
Publisher: Public Library of Science
Author(s): Brian J. Piper, Christy L. Ogden, Olapeju M. Simoyan, Daniel Y. Chung, James F. Caggiano, Stephanie D. Nichols, Kenneth L. McCall, Kenji Hashimoto.
Stimulants are considered the first-line treatment for Attention Deficit Hyperactivity Disorder (ADHD) in the US and they are used in other indications. Stimulants are also diverted for non-medical purposes. Ethnic and regional differences in ADHD diagnosis and in stimulant use have been identified in earlier research. The objectives of this report were to examine the pharmacoepidemiological pattern of these controlled substances over the past decade and to conduct a regional analysis.
Data (drug weights) reported to the US Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System for four stimulants (amphetamine, methylphenidate, lisdexamfetamine, and methamphetamine) were obtained from 2006 to 2016 for Unites States/Territories. Correlations between state level use (mg/person) and Hispanic population were completed.
Amphetamine use increased 2.5 fold from 2006 to 2016 (7.9 to 20.0 tons). Methylphenidate use, at 16.5 tons in 2006, peaked in 2012 (19.4 tons) and subsequently showed a modest decline (18.6 tons in 2016). The consumption per municipality significantly increased 7.6% for amphetamine and 5.5% for lisdexamfetamine but decreased 2.7% for methylphenidate (all p < .0005) from 2015 to 2016. Pronounced regional differences were also observed. Lisdexamfetamine use in 2016 was over thirty-fold higher in the Southern US (43.8 mg/person) versus the Territories (1.4 mg/person). Amphetamine use was about one-third lower in the West (48.1 mg/person) relative to the Northeastern (75.4 mg/person, p < .05) or the Midwestern (69.9 mg/person, p ≤ .005) states. States with larger Hispanic populations had significantly lower methylphenidate (r(49) = -0.63), lisdexamfetamine (B, r(49) = -0.49), and amphetamine (r(49) = -0.43) use. Total stimulant usage doubled in the last decade. There were dynamic changes but also regional disparities in the use of stimulant medications. Future research is needed to better understand the reasons for the sizable regional and ethnic variations in use of these controlled substances.
The prevalence of Attention Deficit Hyperactivity Disorder (ADHD) increased to 11.0% of US children in 2011 of which two-thirds received pharmacotherapy . This was a 41% increase relative to the prevalence in 2003 . A five-fold difference was found in parent reported ADHD medication use between states. ADHD prevalence among children in San Juan was 17% of that in Hartford . Adult ADHD prevalence was 4.4%  and lifetime prevalence was 8.1% . Other variables associated with ADHD medications were male sex and white ethnicity [1,6]. Over three-quarters of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) working group members for ADHD and disruptive behavior disorders had ties to the pharmaceutical industry . The 2013 DSM-5 criteria for ADHD were more inclusive of adult ADHD . There was a 344% increase in women (15–44) with private insurance that filled an ADHD medication prescription between 2003 and 2015 .
Fig 1A shows that amphetamine use increased 2.5 fold from 2006 (7.94 metric tons) to 2016 (19.97). Use of lisdexamfetamine, approved in 2007, steadily increased each year (9.60 in 2016). Methylphenidate consumption was lower in 2006 (16.46), peaked in 2012 (19.39) and declined in the past two years (18.60 in 2016). Amphetamine use overtook methylphenidate in 2016. From 2015 to 2016, there were increases in the average per municipality for amphetamine (+7.6%, p ≤ .0005) and lisdexamfetamine (+5.5%, p ≤ .0005) but a reduction in methylphenidate (-2.7%, p ≤ .0005). Methamphetamine consumption, although very uncommon relative to other agents, increased four-fold from 2015 (26.4 ± 5.6 g) to 2016 (117.8 ± 23.2 g, p < .0005). The primary objective was to examine the temporal pattern of stimulants in the US. This topic is important because these Schedule II drugs have considerable misuse potential and some adverse effects. Use patterns reflect a combination of factors including the broadening ADHD diagnostic criteria and use of the DSM-5  in the US, rates of off-label use for other indications such as obesity and narcolepsy, limited availability of non-pharmacological, but evidence-based, therapies like behavioral parent training and behavioral classroom management [12, 21], patent expirations, the convenience of once daily dosing, and the socio-legal [7, 29], economic [35, 44], or cultural characteristics [15, 34, 45] that influence decision-making about the relative risks and harms for these agents. ADHD diagnoses increased among all children by 42% from 2003 to 2011  and by 83% from 2001 to 2010 among low-income US children . ADHD prevalence may be anticipated to increase further following the 2013 publicatoin of DSM-5 which is more inclusive of adult-ADHD . The US population grew by eight-percent from 2006 to 2016 while methylphenidate use increased 13.0%, amphetamine use doubled and lisdexamfetamine use showed pronounced gains. Total use of these four stimulants doubled. These elevations extend upon other research [1, 9–10, 15, 34]. However, the expansion of the BMI among US children  may have contributed via increased stimulant treatments for obesity or BED. Alternatively, the decline in school time physical activity (eg. recess and gym class) may have contributed to classroom hyperactivity and stimulant prescribing requests from schools. While stimulants may offer substantial benefits to children, for example those in , it is also important to recognize that they are not benign, and that there is substantial diversion and misuse potential for these Schedule II substances [49–53]. Source: http://doi.org/10.1371/journal.pone.0206100