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Concept: Dextroamphetamine

192

Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

Concepts: Dextroamphetamine, Attention, Hyperactivity, Pharmacology, Methylphenidate, Lisdexamfetamine, Amphetamine, Attention-deficit hyperactivity disorder

147

Lisdexamfetamine dimesylate (LDX) is a long-acting d-amphetamine prodrug used to treat attention-deficit/hyperactivity disorder (ADHD) in children, adolescents and adults. LDX is hydrolysed in the blood to yield d-amphetamine, and the pharmacokinetic profile of d-amphetamine following oral administration of LDX has a lower maximum plasma concentration (C max), extended time to C max (T max) and lower inter- and intra-individual variability in exposure compared with the pharmacokinetic profile of an equivalent dose of immediate-release (IR) d-amphetamine. The therapeutic action of LDX extends to at least 13 h post-dose in children and 14 h post-dose in adults, longer than that reported for any other long-acting formulation. Drug-liking scores for LDX are lower than for an equivalent dose of IR d-amphetamine, which may result from the reduced euphorigenic potential associated with its pharmacokinetic profile. These pharmacokinetic and pharmacodynamic characteristics of LDX may be beneficial in the management of symptoms in children, adolescents and adults with ADHD.

Concepts: Pharmacology, Amphetamines, Methylphenidate, Prodrug, Dextroamphetamine, Attention-deficit hyperactivity disorder, Amphetamine, Lisdexamfetamine

28

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects individuals across the lifespan. ADHD medication use among pregnant women is increasing (1), but consensus about the safety of ADHD medication use during pregnancy is lacking. Given that nearly half of U.S. pregnancies are unintended (2), and early pregnancy is a critical period for fetal development, examining trends in ADHD medication prescriptions among reproductive-aged women is important to quantify the population at risk for potential exposure. CDC used the Truven Health MarketScan Commercial Database* for the period 2003-2015 to estimate the percentage of women aged 15-44 years with private employer-sponsored insurance who filled prescriptions for ADHD medications each year. The percentage of reproductive-aged women who filled at least one ADHD medication prescription increased 344% from 2003 (0.9% of women) to 2015 (4.0% of women). In 2015, the most frequently filled medications were mixed amphetamine salts, lisdexamfetamine, and methylphenidate. Prescribing ADHD medications to reproductive-aged women is increasingly common; additional research on ADHD medication safety during pregnancy is warranted to inform women and their health care providers about any potential risks associated with ADHD medication exposure before and during pregnancy.

Concepts: Uterus, Fetus, Embryo, Dextroamphetamine, Medical prescription, Prescription drug, Amphetamine, Pregnancy

24

Lisdexamfetamine dimesylate (LDX) and d-amphetamine pharmacokinetics were assessed in individuals with normal and impaired renal function after a single LDX dose; LDX and d-amphetamine dialyzability was also examined.

Concepts: Dextroamphetamine, Lisdexamfetamine

7

Insufficient sleep is a serious problem in adolescents and school start time is thought to be a key contributor. This study provided the first comprehensive assessment of school start times across Canada and examined whether school start times were associated with sleep duration and tiredness among adolescents. We collected information on school start times from 362 schools that participated in the 2013/2014 Health Behaviour in School-aged Children study. We calculated sleep duration from weekday bedtime and wake time reported by 29 635 students (aged 10-18 years). We classified weekday sleep as sufficient if it met national recommendations, and used data on self-reported tiredness at school in the morning. Random-effects regression models estimated the association of school start time with sleep duration, sleep sufficiency and tiredness. On average, schools started at 08:43 hours. Students slept an average of 8:36 h on weekdays and 69% met sleep duration recommendations, but 60% reported feeling tired in the morning. Every 10-min delay in school start time corresponded with 3.2 [95% confidence interval (CI): 2.0, 4.5] additional minutes of sleep, a 1.6% (95% CI: 0.5, 2.8) greater probability of sufficient sleep and a 2.1% (95% CI: 1.0, 3.2) smaller probability of feeling tired at school in the morning. Students from schools that started later slept longer, were more likely to meet sleep recommendations and were less likely to report feeling tired in the morning. The study adds weight to the mounting evidence that delaying school start time benefits adolescent sleep.

Concepts: School, High school, Dextroamphetamine, Somnolence, Statistics, Time, Education, Sleep

5

Amphetamine is the most prevalent prescription stimulant in the United States, both medically and nonmedically. Reliable data on nonmedical use is needed to continue to inform prevention. To determine whether adolescents accurately self-report nonmedical amphetamine use, we compared self-reports of nonmedical amphetamine use and nonmedical Adderall use in a national sample.

Concepts: Basketball, U.S. state, Poverty in the United States, Dextroamphetamine, Adderall, High school, United States, Amphetamine

3

Attention Deficit Hyperactivity Disorder (ADHD) medication use is on the rise in the United States. The most widely used ADHD medications are the amphetamine-type compounds Adderall (mixed amphetamine salts) and Ritalin (methylphenidate). According to survey data ADHD medications are used as a study drug or “Smart Drug” by students without a prescription on college campuses. Survey data of non-prescribed drug use has limitations with accurate reporting and no empirical data of usage exists in the literature. This study looks for trends in the use of these drugs on a college campus among low-stress and high stress periods. The metabolites of these two drugs, amphetamine and ritalinic acid, are quantified in campus wastewater using solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Trends show a possible increase in amphetamine levels during periods of high stress such as midterms, the last week of classes and finals week over levels from the baseline low stress weeks such as the first week of classes. Both semesters from the 2011-12 academic year were studied and the highest increase over baseline (760%) occurred during finals week of the second semester. Ritalinic acid levels gradually climbed first semester but had no obvious periodic trend second semester.

Concepts: Norepinephrine, Attention, Dextroamphetamine, Hyperactivity, Dopamine, Methylphenidate, Attention-deficit hyperactivity disorder, Amphetamine

2

We examined how purging behaviors relate to subjective sleep quality and sleep patterns and how symptoms of disordered eating behaviors relate to global sleep quality in female patients with anorexia nervosa (AN).

Concepts: Dextroamphetamine, Memory, Symptoms, Eating disorders, Observational study

1

As postsecondary students' use of “study drugs” becomes more popular with increasingly reported negative effects on health and academic performance, failing prohibitionist policies to reduce consumption, and ambiguity in literature towards best practices to address this population, we present a literature review that seeks effective solutions educational institutions can apply to improve outcomes for students who use drugs. Motivations for use, effects of the substances, an analysis of efforts to control use from educational institutions, and suggestions on promoting most effective outcomes based on harm reduction, are described. Theory, quantitative, and qualitative works from systematic reviews, cohort studies, and epidemiological assessments are examined on the “study drugs” methylphenidate, dextroamphetamine, and amphetamine, also known as Adderall, Ritalin, Focalin, and Concerta. There is a focus on postsecondary students ages 18-25 in North America. Results show important risk factors for drug use including low perceived self-efficacy or enjoyment in courses, poor accommodation of special needs, reliance on external validation, having a low GPA, and experiencing a mental health issue. There is much misconception on the health and academic effects of these drugs in literature, among students, and on online knowledge sources. We suggest these drugs do not improve GPA and learning, while they might temporarily increase memory, but with detrimental negative health effects. Campaigns that address underlying factors of use can be most successful in mitigating harms.

Concepts: Attention-deficit hyperactivity disorder, Norepinephrine, Dopamine, Epidemiology, Education, Methylphenidate, Dextroamphetamine, Amphetamine

1

Prescription stimulants, including methylphenidate (e.g., Ritalin) and amphetamine compounds (e.g., dextroamphetamine; Adderall), have been approved by the U.S. Food and Drug Administration for the treatment of attention-deficit/hyperactivity disorder (ADHD) and are classified by the United States Drug Enforcement Administration as Schedule II medications because of their high potential for abuse and dependence (Drug Enforcement Administration, U.S. Department of Justice, 2015). Despite the potential health and judicial consequences, misuse of prescription stimulants, typically defined as taking stimulants without a valid prescription, or use of stimulants other than as prescribed, has become a serious problem in the United States and abroad, especially on college campuses. The purpose of the present article is to review historical information concerning prescription stimulants and to summarize the literature with respect to misuse among adults, particularly college students, including risk factors, mediators and moderators, and motivations for prescription stimulant misuse. In addition, evidence is presented concerning the question of whether prescription stimulants truly enhance cognitive functioning in individuals with and without ADHD, and the ethical and professional implications of these findings are explored. Lastly, recommendations for addressing prescription stimulant misuse and suggestions for future research are advanced. (PsycINFO Database Record

Concepts: Food and Drug Administration, Narcolepsy, United States, Dextroamphetamine, Dopamine, Methylphenidate, Attention-deficit hyperactivity disorder, Amphetamine