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In 2006, the United States Department of Defense developed for the first time official criteria for the use of psychopharmaceuticals "in theater"-in the physical and tactical spaces of military operations including active combat. Based on fieldwork with Army soldiers and veterans, this article explores the transnational and global dimensions of military psychopharmaceutical use in the post-9/11 wars. I consider the spatial, material, and symbolic dimensions of what I call "pharmaceutical creep"-the slow drift of psychopharmaceuticals from the civilian world into theater and into the military corporate body. While pharmaceutical creep is managed by the U.S. military as a problem of gatekeeping and of supply and provisioning, medications can appear as the solution to recruitment and performance problems once in theater. Drawing on soldiers' accounts of medication use, I illuminate the possibilities, but also the frictions, that arise when routine psychopharmaceuticals are remade into technologies of global counterinsurgency., (© 2019 by the American Anthropological Association.)

Objective: To examine real-world prescription medication usage among commercially-insured adults with attention deficit/hyperactivity disorder (ADHD) in the US., Methods: Adults with ADHD who received ≥1 ADHD medication during 2013 were identified from a large US claims database. Combination therapy was defined as an overlap of ≥30 days between the index (first treatment ≥30 days in 2013) and another medication(s). Patients were classified into six groups: long-acting (LA) monotherapy, short-acting (SA) monotherapy, LA + LA, SA + SA, LA + SA, and >2 therapies. Analyses compared baseline characteristics by regimen, ranked combination regimens, and estimated daily average consumption (DACON) for monotherapy users., Results: Of 206,443 adults with ADHD (mean age = 32.9 years; 51.6% female), 56.9% used LA monotherapy, 30.7% SA monotherapy, and 12.5% used combination therapies (LA + SA: 10.3%; LA + LA: 1.3%; SA + SA: 0.4%; >2 therapies: 0.5%). Extended-release mixed amphetamine salts (MAS-XR, 39.2%) and lisdexamfetamine (LDX, 31.5%) were the most common LA monotherapies. Nearly all SA monotherapy patients received immediate-release mixed amphetamine salts (MAS-IR; 81.7%). The top three therapies among combination categories were: (a) LA + LA: branded MAS-XR + generic MAS-XR (13.7%), LDX + generic MAS-XR (10.8%), LDX + guanfacine ER (10.7%); (b) SA + SA: generic MAS-IR + clonidine IR (33.5%), generic MAS-IR + generic MPH SA (17.9%), branded MAS-IR + generic MAS-IR (11.1%); (c) LA + SA: generic MAS-XR+/-IR (39.2%), LDX + generic MAS-IR (16.7%), LA + SA generic MPH (12.6%). Among monotherapy users, DACON was 1.2 ± 0.6 (LA) and 2.1 ± 0.9 (SA) tablets., Conclusions: There is significant treatment heterogeneity among US adults with ADHD. A sizable proportion of patients received monotherapies at above the recommended dosages or combination therapies, suggesting existing single-tablet regimens may not meet patients' needs.

Objective: To compare treatment persistence in attention-deficit/hyperactivity disorder (ADHD) of patients initiated on lisdexamfetamine (LDX) vs other ADHD medications., Methods: A large US administrative claims database was used to select ADHD patients who initiated an ADHD medication (index treatment) during/after 2007. Patients were classified, based on age and previous treatment status, as treatment-naïve or previously treated children and adolescents (6-17 years) and treatment-naïve or previously treated adults (18 years and older). Furthermore, patients were classified into seven mutually exclusive treatment groups, based on their index treatment: LDX, atomoxetine (ATX), osmotic-release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate short-acting (MPH SA) and long-acting (MPH LA), and amphetamine/dextroamphetamine short acting (AMPH SA) and long-acting (AMPH LA). Treatment persistence, analyzed through discontinuation (interruption of the index treatment for ≥30 consecutive days), was compared between treatment groups using multivariate Cox proportional hazards. Patients were followed until first treatment discontinuation or up to 12 months after the initiation of the index treatment, whichever occurred first., Results: Among children and adolescents, LDX patients had a significantly lower discontinuation rate compared to other treatment groups (range hazard ratios [HRs]; 1.04-2.26; all p < 0.05), except when compared to treatment-naïve patients on ATX and OROS MPH, where no statistically significant differences were found and where LDX had a higher risk of discontinuation, respectively. Among adults, LDX patients had a significantly lower discontinuation rate compared to patients in other treatment groups (range HR; 1.14-1.86; all p < 0.05), except for the comparison with AMPH LA patients, where differences were not statistically significant., Limitations: This study did not control for ADHD severity., Conclusion: LDX-treated patients were associated with higher persistence compared to patients initiated on other ADHD medications, except for the comparisons with OROS MPH and ATX treated patients in treatment-naïve children and adolescents and AMPH LA-treated patients in adults.

Objective: This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices., Methods: Data obtained from the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physicians, were used to examine trends in office visits by children and adolescents (under age 18) during which ADHD was treated with Adderall, other psychostimulants, or atomoxetine. Segmented time series regressions were conducted to determine changes in use associated with three advisories issued between 2005 and 2007., Results: In 2004, before the first FDA advisory, Adderall accounted for 36% of ADHD pharmacotherapy treatment visits. Other stimulants accounted for 46%, and atomoxetine accounted for 19%. Overall pharmacotherapy treatment rates were stable over the study period, but by 2008 the treatment visits accounted for by Adderall (that is, market share) declined to 24%, and the market share for atomoxetine declined to 8%. The market share for substitute therapies-clonidine, guanfacine, and bupropion-was stable over this period, ranging from 5% to 7%. Despite the declines in the use of Adderall and atomoxetine over the study period, results from the regression models suggest that the advisories did not have a statistically significant effect on ADHD medication prescribing., Conclusions: FDA advisories regarding potential cardiovascular and other risks of ADHD medications had little discernible incremental effect on the use of these medicines in this nationally representative ambulatory audit.

Objective: The authors investigated trends and patterns in stimulant treatment of adults visiting office-based medical practices in the United States., Method: A time series analysis of data from the 1994 to 2009 National Ambulatory Medical Care Surveys (no. of visits = 372,702) was performed, focusing on adult (aged ≥ 18 years) visits in which stimulant medications (amphetamine salts, methylphenidate, or pemoline) were prescribed. The authors computed trends in the percentage of visits in which a stimulant was prescribed stratified by background and clinical patient characteristics. Results are reported as odds ratios (ORs) over the 1994 to 2009 period. The authors also compare visits to psychiatrists and nonpsychiatrist physicians that yielded a stimulant prescription to an adult., Results: The percentage of visits in which stimulants were prescribed increased from 0.11% (1994-1997) to 0.70% (2006-2009) (OR = 13.72, 95% confidence interval [CI], 9.40-20.03). Among adults aged 18 to 29 years, the corresponding increase in stimulant visits was from 0.17% to 1.83% (OR = 30.14, 95% CI, 15.84-57.36). Stimulant prescriptions increased significantly more rapidly among visits without a clinical ADHD diagnosis (OR = 11.86, 95% CI, 7.49-18.80) than among visits with such a diagnosis (OR = 5.45, 95% CI, 2.96-10.04) (interaction P = .04) and among visits to nonpsychiatrist physicians (OR = 21.54, 95% CI, 12.84-36.12) than psychiatrists (OR = 10.64, 95% CI, 6.72-16.86) (interaction P = .03). By 2006-2009, nonpsychiatrist physicians provided most (57.7%) of the stimulant prescriptions linked to adult office-based visits. As compared with psychiatrists, nonpsychiatrist physicians diagnosed ADHD in a significantly smaller proportion of their adult visits in which stimulants were prescribed (62.5% vs 34.4%, P < .0001)., Conclusions: Between 1994 and 2009, there was a substantial increase in stimulant prescriptions during adult outpatient visits, especially during visits of younger adults. The increase in stimulant treatment occurred significantly more rapidly in the practices of nonpsychiatrist physicians than in those of psychiatrists., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

The use of stimulant medications for the treatment of cocaine dependence is an evolving scientific line of research. To date, the most promising results are with the higher-potency medications, the amphetamine analogues, or a combination of a dopaminergic medication with a contingency management behavioral intervention. The development of effective pharmacotherapies for opioid and nicotine dependence using an agonist replacement approach suggests that these promising findings needs to continue to be vigorously investigated. In clinical trial reports, there are very few instances of cardiovascular adverse events, which suggests that for well-selected patients with cocaine dependence, stimulant replacement therapy can be safe. However, clinical trial eligibility criteria excludes most high-risk patients from participating, and introducing stimulant substitution to the wider treatment community would likely expose more vulnerable patients to the medical risks associated with stimulant treatment while using cocaine. As treatment development research moves forward, attention must be paid to helping clinicians select patients who are most likely to benefit from stimulant substitution treatment and how to identify those at risk. An additional concern with the use of stimulant medication treatment of cocaine dependence is prescribing controlled substances for patients with active substance use disorders. Again, within a clinical trial, medication supplies are monitored and distributed carefully in small quantities. In a community setting, misuse or diversion will be risks associated with prescribing controlled substances to patients with addictive disorders, but therapeutic strategies for monitoring and limiting that risk can be implemented. Psychostimulant pharmacotherapy is a promising line of research for the treatment of cocaine dependence, a condition for which no effective pharmacotherapy has been identified. Further research is required to confirm positive results from single-site trials, in particular the study of amphetamines as a treatment for cocaine dependence. As this literature evolves, strategies to manage the risk of prescribing controlled substances to patients with addictive disorders need to be tested and refined. Biases against using controlled substances as a treatment for cocaine dependence should be challenged, much in the way the use of agonist treatment transformed the treatment of opioid dependence despite initial resistance from the field.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood, and congenital heart disease (CHD) is the most common form of birth defect. Children with CHD are at increased risk for neurodevelopmental disorders such as ADHD. Stimulant medications, specifically methylphenidates and amphetamines, are frequently prescribed and effective in reducing the symptoms of ADHD. Despite their efficacy and long history of use, the safety of these medications has recently come into question due to isolated reports describing sudden unexplained death of children undergoing treatment. This review summarizes the current literature on the cardiovascular risks associated with the use of pharmacologic therapy for ADHD, with an emphasis on patients who had CHD.

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research., ((PsycINFO Database Record (c) 2011 APA, all rights reserved).)

Purpose: To describe the design and rationale of an investigator-initiated observational study to examine the cardiovascular safety of the following commonly-used medications to treat attention deficit hyperactivity disorder (ADHD): amphetamines, methylphenidate, and atomoxetine., Methods: We are conducting an observational cohort study using data from five large Medicaid programs and the HealthCore Integrated Research Database (HIRD(SM)), which is derived from administrative data from commercial health plans. Our primary outcomes of interest are (1) sudden death/ventricular arrhythmia, (2) stroke, (3) myocardial infarction, and (4) stroke or myocardial infarction as a composite outcome. These claims diagnoses have been previously validated in adults, and the positive predictive value in children will be examined as part of this study. Secondary outcomes are (1) all-cause death, (2) non-suicide death, and (3) non-accident death. All design decisions have been made to minimize bias toward the null. Based on our pilot data, we expect to have at least 90% power to detect a minimum detectable hazard ratio (HR) of 3.0 in children and adolescents who initiate an ADHD medication for each outcome of interest (except for MI, for which the expected minimum detectable HR is 7.9). The expected minimum detectable HR is 1.7 for each outcome for adult incident ADHD medication users., Results: Forthcoming., Conclusions: Potential limitations to this study include a low expected event rate in children and adolescents, potentially incomplete ascertainment of outcomes, and potential confounding by unmeasured variables. Nevertheless, this study will provide important information about the cardiovascular safety of ADHD medications., ((c) 2010 John Wiley & Sons, Ltd.)

Objective: The authors used quantitative and qualitative methodologies to investigate college students' perceptions and use of illegal Attention Deficit Hyperactivity Disorder (ADHD) stimulants during spring and summer 2006., Participants: From fall 2005 through fall 2006, the authors studied 1,811 undergraduates at a large, public, southeastern research university in the United States., Methods: The authors administered surveys to these students and conducted 175 in-depth interviews., Results: Of the study participants, 34% reported the illegal use of ADHD stimulants. Most illegal users reported using ADHD stimulants primarily in periods of high academic stress and found them to reduce fatigue while increasing reading comprehension, interest, cognition, and memory. Furthermore, most had little information about the drug and found procurement to be both easy and stigmafree., Conclusions: This study supplies a rich understanding of the growing national trend of illegal ADHD stimulant use. The authors discuss strategies for stemming the tide of ADHD stimulant use.

Attention-deficit/hyperactivity disorder (ADHD) holds the distinction of being the most extensively studied pediatric mental disorder and one of the most controversial, in part because it is also the most commonly diagnosed mental disorder among minors. Currently, almost 8% of youth aged 4 to 17 years have a diagnosis of ADHD, and approximately 4.5% both have the diagnosis and are using a stimulant (methylphenidate or amphetamine) as treatment for the disorder. Yet a diagnosis of ADHD is not simply a private medical finding; it carries with it a host of policy ramifications. The enduring controversy over ADHD in the public arena therefore reflects the discomfort over what happens when science is translated into policies and rules that govern how children will be treated medically, educationally, and legally. This article (1) summarizes the existing knowledge of ADHD, (2) provides the relevant history and trends, (3) explains the controversy, (4) discusses what is and is not unique about ADHD and stimulant pharmacotherapy, (5) outlines future directions of research, and (6) concludes with a brief analysis of how two North Carolina counties have established community protocols that have improved the screening, treatment, and societal consensus over ADHD and stimulants.

Objective: Compare observed and forecasted efficacy of mixed amphetamine salts extended release (MAS-XR; Adderall) with atomoxetine (Strattera) in ADHD children., Method: The authors analyze data from a randomized, double-blind, multicenter, parallel-group, forced-dose-escalation laboratory school study of children ages 6 to 12 with ADHD combined or hyperactive/impulsive type. Primary efficacy measures are attention and deportment scores on the SKAMP behavioral rating scale, and secondary efficacy measures are academic performance scores from the PERMP test., Results: MAS-XR elicits greater improvements than atomoxetine in each domain within 3 weeks of treatment, including attention, number of math problems attempted and correct, and overall clinical functioning. Treatment differences in each outcome measure at subsequent weeks are projected from generalized estimating equations to become greater with the duration of extension of the treatment regimen., Conclusion: This study suggests that relative advantages of MAS-XR seen in the first 3 weeks are likely to be maintained in subsequent weeks.

This article uses an historical case study to describe the influence of social and contextual factors on the adoption of somatic approaches to children's misbehavior. The child guidance movement and the emergence of medicalized residential treatment facilities for children influenced the theoretical orientations of physicians treating children's behavior disorders in the United States in the 1930s. Charles Bradley and his colleagues at the Bradley Home in Rhode Island defined behavior disorders in social terms but investigated and treated misbehavior with somatic tools. The use of amphetamines and the electroencephalogram reorganized concepts of maladjustment along neurological lines, even as the research relied on the Home's social priorities. Electroencephalographic investigations especially shaped an organic concept of misbehavior. Ultimately, the somatic orientation obscured the central role of local context in Bradley Home physicians' research., ((c) 2006 Wiley Periodicals, Inc.)

Objective: Stimulant medications, such as methylphenidate and amphetamines, are commonly prescribed to treat attention deficit hyperactivity disorder. Stimulant use increased fourfold from 1987 (0.6%) to 1996 (2.4%) among subjects 18-year-old and younger in the U.S. The aim of this study was to determine whether pediatric use of stimulants continued to rise during the period 1997-2002., Method: The Medical Expenditure Panel Survey (MEPS) database for the years 1997-2001 was analyzed. The MEPS is a yearly survey of a nationally representative sample of civilian, noninstitutionalized U.S. households, conducted by the U.S. Agency for Health Care Research and Quality. Previously reported estimates from the 1996 MEPS and the 1987 National Medical Expenditure Survey, the predecessor to MEPS, were also replicated to compare recent trends to changes between 1987 and 1996., Results: The prevalence use of stimulants among subjects under 19 years of age was 2.7% (95% C.I. 2.3-3.1) in 1997 and 2.9% (95% C.I. 2.5-3.3) in 2002, with no statistically significant change during these 6 years. Likewise, when pooling data across years and comparing the rate in 1997-1998 (2.8%) with the rate in 2001-2002 (3.0%), no statistically significant changes emerged. Use was highest among 6-12 year olds (4.8% in 2002), as compared with 3.2% among 13-19 year olds and 0.3% among children under 6. An estimated 2.2 million (95% C.I. 1.9-2.6) children received stimulant medication in 2002 as compared to 2.0 million (95% C.I. 1.7-2.3) in 1997., Conclusions: The steep increase in the utilization of stimulants among children 18 years and younger that occurred over the 1987-1996 period attenuated in the following years through 2002, and has remained stable among very young children.

Objective: To assess the safety, tolerability, and effectiveness of mixed amphetamine salts extended release (MAS XR) in school-age children with attention-deficit/hyperactivity disorder (ADHD) treated in a community practice setting., Methods: Children aged 6-12 years (N = 2968) with DSM-IV-defined ADHD entered a 9-week prospective, open-label, non-comparative study of MAS XR at 386 sites. For at least 2 weeks before enrollment, subjects with well-controlled ADHD received their consistent dose of previously prescribed psychostimulant. Subsequently, this regimen was converted to an equivalent once-daily dose of 10-, 20-, or 30-mg MAS XR, according to a conversion algorithm. Tolerability and safety were assessed based on reported treatment-emergent adverse events and observed changes in vital signs and body weight. Effectiveness was assessed using a parent-completed Conners' Global Index Scale (CGIS-P) measured 8 and 12 h postdose and a clinician-scored Clinical Global Impressions-Improvement (CGI-I) scale after 1, 3, and 7 weeks of treatment. The dose of study medication could be adjusted at weeks 1 and 3 to a maximum of 40 mg/day. Outcome analyses used an intent-to-treat methodology, with last observations carried forward., Results: Statistically significant improvement in ADHD behavior 8 and 12 h postdose occurred during the first week of treatment and was maintained through study endpoint (p < 0.0001). Results of the investigator-rated CGI-I at weeks 1, 3, and 7 were consistent with the parent-rated CGIS-P results, indicating that MAS XR treatment significantly improved symptoms compared with the baseline stimulant regimen (p < 0.0001). The incidence of treatment-related adverse events was low, and most AEs were mild in intensity., Conclusion: MAS XR 10-40 mg is a safe and effective once-daily medication for treatment of children with ADHD in a community practice setting. ADHD symptoms may be further reduced by converting from current pharmacotherapy to an optimally titrated dose of MAS XR.

Objective: To provide a national profile of the area variation in per-capita psychostimulant consumption in the U.S., Methods: We separated 3030 U.S. counties into two categories of 'low' and 'high' per-capita use of attention deficit hyperactivity disorder (ADHD) drugs (based on data from the Drug Enforcement Administration), and then analyzed them on the basis of their socio-demographic, economic, educational and medical characteristics., Results: We found significant differences and similarities in the profile of counties in the U.S. that are above and below the national median rate of per-capita psychostimulant use (defined as g/per 100K population). Compared to counties below the median level, counties above the median level have: significantly greater population, higher per-capita income, lower unemployment rates, greater HMO penetration, more physicians per capita, a higher ratio of young-to-old physicians and a slightly higher students-to-teacher ratio., Conclusions: Our analysis of the DEA's ARCOS data shows that most of the significant variables correlated with 'higher' per-capita use of ADHD drugs serve as a proxy for county affluence. To provide a more complex, multivariate analysis of the area variation in psychostimulant use across the U.S.-which is the logical next step-requires obtaining price data to match the DEA's quantity data.

The use of drugs and supplements to enhance performance has become a part of mainstream athletics. Many team physicians and sports medicine practitioners are unfamiliar with the benefits and risks of these products and thus are unable to educate young athletes on this topic. In spite of numerous reports on the health risks of anabolic steroid use, 1 to 3 million Americans have used them. Human growth hormone has been tried by up to 5% of 10th graders, although no scientific study has shown that it is an effective performance-enhancing drug. Amphetamines and similar compounds may be the most widely abused drug in baseball; recently, they have come under increased scrutiny in sport. Erythropoietin is a highly effective aerobic enhancer that has been linked to multiple deaths in cyclists and other endurance athletes. The neutraceutical industry, led by supplements such as creatine, ephedra, and androstenedione, remains unregulated by the Food and Drug Administration and has serious issues with quality and side effects. An understanding of these products is essential for the sports medicine practitioner to provide sound, safe advice to the athlete.

Background: The use of appetite suppressants in Europe has been associated with the development of primary pulmonary hypertension (PPH). Recently, fenfluramine appetite suppressants became widely used in the United States but were withdrawn in September 1997 because of concerns over adverse effects., Materials and Methods: We conducted a prospective surveillance study on patients diagnosed with pulmonary hypertension at 12 large referral centers in North America. Data collected on patients seen from September 1, 1996, to December 31, 1997, included the cause of the pulmonary hypertension and its severity. Patients with no identifiable cause of pulmonary hypertension were classed as PPH. A history of drug exposure also was taken with special attention on the use of antidepressants, anorexigens, and amphetamines., Results: Five hundred seventy-nine patients were studied, 205 with PPH and 374 with pulmonary hypertension from other causes (secondary pulmonary hypertension [SPH]). The use of anorexigens was common in both groups. However, of the medications surveyed, only the fenfluramines had a significant preferential association with PPH as compared with SPH (adjusted odds ratio for use > 6 months, 7.5; 95% confidence interval, 1.7 to 32.4). The association was stronger with longer duration of use when compared to shorter duration of use and was more pronounced in recent users than in remote users. An unexpectedly high (11.4%) number of patients with SPH had used anorexigens., Conclusion: The magnitude of the association with PPH, the increase of association with increasing duration of use, and the specificity for fenfluramines are consistent with previous studies indicating that fenfluramines are causally related to PPH. The high prevalence of anorexigen use in patients with SPH also raises the possibility that these drugs precipitate pulmonary hypertension in patients with underlying conditions associated with SPH.

Obesity is a common and serious health problem in the United States. Excess weight is associated with an increased mortality rate, as well as such risk factors as hypertension, hyperlipidemia and diabetes mellitus. Numerous treatments are available for obesity. Behavioral therapy, surgery and pharmacologic treatment have been used with varying degrees of success. Pharmacologic therapy includes primarily noradrenergic agents and/or serotonergic agents. Newer preparations are currently under development. Behavior modification, including regular exercise and the development of healthy eating habits remains the best hope for long-term weight loss. However, surgery or medication can be useful in specific circumstances.

Fenetylline (CAPTAGON) is included in a list of compounds to be considered by a World Health Organization (WHO) Expert Committee in April 1985 for possible international scheduling under the Convention on Psychotropic Substances, 1971. For over 23 years, this central stimulant has been used therapeutically in hyperkinetic children and other indications in place of amphetamines and other central stimulants with higher risk levels. In good correspondence with recent animal data fenetylline also shows significant qualitative and quantitative differences compared to amphetamine in man. It has few adverse side effects, a lower abuse potential and little actual abuse compared to amphetamine. Thus its benefit/risk assessment is substantially more favourable than that of other central stimulants. For proper therapeutic use of the substance, prescription status is or should be required by national authorities.