In dosages prescribed for medical indications, some evidence indicates that amphetamine does not affect nursing infants adversely. The effect of amphetamine in milk on the neurological development of the infant has not been well studied. Large dosages of amphetamine might interfere with milk production, especially in women whose lactation is not well established. Breastfeeding is generally discouraged in mothers who are actively abusing amphetamines.[1-3] One expert recommends that amphetamine not be used therapeutically in nursing mothers.[4]

A 4-year-old, female-spayed, mixed breed dog, weighing 24.2 kg, was presented for acute ingestion of ~12.3 mg/kg of Adderall XRⓇ, an extended-release amphetamine medication. In dogs, the oral median lethal dose for amphetamines ranges anywhere from 9-11 mg/kg to 20-27 mg/kg. On presentation, the patient was agitated, tachycardic and hypertensive. Initial treatment was instituted with intravenous lipid emulsion (IVLE) therapy, and baseline and post-treatment amphetamine concentrations were quantified in serum and plasma. In both serum and plasma, post-IVLE concentrations of amphetamine were lower 1 h after treatment and IVLE was the only treatment instituted during this time. The dog improved significantly while in hospital and was discharged <24 h after presentation. This is the first known reported use of IVLE for treatment of amphetamine toxicosis with documented decreases in both serum and plasma amphetamine levels shortly after administration of IVLE.

Objective: The purpose of this study was to compare the pharmacokinetics of a new extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended-release mixed amphetamine salts product, Adderall XR®. Method: In this single-dose, open-label, randomized, two-period, two-treatment crossover study, 42 healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg Adderall XR capsule in another period (both containing 18.8 mg of amphetamine base) under fasted conditions. Blood samples were analyzed for d- and l-amphetamine concentrations, and pharmacokinetic parameters Cmax, AUC0-5, AUC5-last, and AUCinf were calculated to determine bioequivalence. Safety was monitored throughout the study. Results: The 90% confidence intervals (CIs) for the log-transformed Cmax, AUC0-5, AUC5-last, and AUCinf fell within the accepted 80% to 125% range for establishing bioequivalence for d- and l-amphetamine. The most common adverse events were nausea and decreased appetite. Conclusion: AMP XR-OS is bioequivalent to Adderall XR in healthy adult participants.

The pediatric clinics of the Michigan State University College of Human Medicine (MSU-CHM) consist of academic pediatricians serving two clinics with a patient population of 5200. The internal quality measures published by the MSU health team had consistently indicated our generic medications prescription rate to be very low, with an average of about 21% for the years 2009, 2010, and 2011. There was an earnest need to increase our generic medication prescription rates, which is considered an indicator of good practice. The stakeholders identified were physicians, nurses, care managers, and the health information technology (HIT) team. The purpose of the project was to increase the prescribing rate of viable low cost and approved generic medications for the patients of the MSU-CHM general pediatric clinics. The stakeholders regularly met every few months to work on increasing the generic medication prescription rates based on the PDSA cycle. Help was sought from HIT to identify and acquire the top 10 brand names the group was prescribing along with individual provider data. The team reviewed the brand names most prescribed, and made a recommendation that the best group to target were the stimulant medications, allergy and asthma medications, and other psychotropics. The HIT team was then requested to add the available generics for all stimulant medications, asthma medications, and others in the electronic medical record (EMR). They were also clearly marked for ease of use, for example: amphetamine-dextroamphetamine extended release "generic for Adderall XR." It was decided that providers would prescribe all stimulants as a generic, unless not available, and nurses would change each brand name of stimulants to a generic every time they refilled a medicine, based on a protocol outlining the appropriate generic medications corresponding to the respective brand names. The physicians and nurses were also urged to discuss with the patients the substitution process and answer any questions from parents. Monthly reports were obtained from the HIT about our progress. After 12 months of implementing this project, the overall generic prescription rate increased from 20% at the end of first quarter 2012 to 53% at the end of 12 months, and 65.5% at the end of two years. This was well above the MSU health team (about six large group practices) primary care average of 34.6%. All brand name medication prescription rates were also decreased. This is a positive outcome for this project in a relatively short period of time, and a further plan will be to repeat the cycle and continue to improve on the generic prescription rate, thereby saving valuable dollars spent on health care.

Amphetamine-derived medications are being prescribed with increasing frequency to younger pediatric patients to treat attention deficit hyperactivity disorder. Although choreiform movements were reported in adults with amphetamine abuse and in those under therapeutic treatment for attention deficit hyperactivity disorder, previous literature concerning the pediatric population is spare. We describe two children who developed chorea after ingesting amphetamine-derived medications prescribed to treat attention deficit hyperactivity disorder. Patient 1, a 10-year-old boy, accidently received an extra dose of lisdexamfetamine dimesylate the night before the onset of acute chorea involving his arms, legs, and trunk. Patient 2, an 8-month-old boy, accidentally ingested his stepbrother's mixed amphetamine salts (Adderall XR) and developed acute chorea. Benzodiazepines, diphenhydramine, benztropine, and opioids did not suppress the chorea in either case. The 10-year-old received haloperidol, which significantly improved his abnormal findings, and he returned to baseline in approximately 48 hours. The 8-month-old was observed in the pediatric intensive care unit, and his signs resolved by 72 hours. Our cases demonstrate that choreiform movements of sustained duration can occur in children with acute supratherapeutic ingestions of amphetamine-derived medications.

Motor difficulties are common in children with Attention Deficit Hyperactivity Disorder (ADHD). Although preliminary evidence has suggested that methylphenidate can improve the motor skills in children with ADHD and Developmental Coordination Disorder (DCD), the effect of stimulant medication on motor performance in children newly diagnosed with ADHD with or without motor impairment remains unclear. A cohort study of 49 medication-naïve children (39 male; mean age 8.4±1.3 years) with ADHD was conducted. Children were evaluated using the Movement Assessment Battery for Children and the developmental test of visual motor integration at diagnosis and again three months following daily treatment with a stimulant medication. Motor difficulties were highly present at baseline (73.5%) but resolved in a subset after treatment with stimulant medication, suggesting that their motor difficulties may be attributed in part to their attentional problems. Nevertheless, motor impairment persisted in 55.1% of the sample. The severity of the behavioural symptoms was significantly associated with balance skills in children without motor impairments (r(2)=0.30, p<0.01) and with visual motor integration skills in children with persisting motor difficulties (r(2)=0.27, p<0.01). Attentional difficulties negatively affect the motor skills of children with ADHD. Following the use of stimulant medication, an important subset continued to demonstrate motor difficulties. The improvement in behaviour was insufficient to resolve motor problems and these children should therefore be targeted for rehabilitation services.

Adderall XR is commonly prescribed for children and adolescents with attention deficit/hyperactivity disorder. We present a case of a 15-year-old male who suffered a myocardial infarction after starting Adderall XR. Patient was otherwise in good health with no previous cardiac abnormalities. Cardiac catheterization was normal, and etiology was presumed to be secondary to acute vasospasm. The patient improved with cessation of medication. Physicians need to carefully screen patients for cardiac abnormalities prior to starting amphetamine-based medications.

To examine the changes in partially responsive anxiety symptoms utilizing adjunctive treatment with the mixed amphetamine salt extended release (Adderall XR, MAX-XR) in the treatment of adult ADHD patients, with comorbid refractory anxiety. Consenting adult patients (n = 32) with confirmed diagnosis of generalized anxiety (GA) and comorbid (ADHD) participated in this open-label study. All patients had significant comorbid anxiety symptoms (HAM-A > 7) and failed to respond to 8-week trials of Serotonin Reuptake Inhibitors (SSRIs) or Norepinephrine Reuptake inhibitors (SNRIs). All patients were treated with the "Mixed Amphetamine salts Extended Release Adderall XR, (MAS-XR), as adjunctive to SSRIs or to SNRIs and were followed for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression severity subscale (CGI-S). Other scales included the Hamilton Anxiety Scale (HAM-A), the adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist, and Sheehan's disability scale. Baseline measures prior to the treatment with MAS-XR were compared to those at 4, 8, and at 12 weeks of treatment. Monitoring for pulse, blood pressure, and weight changes was carried out at baseline and at end point. All patients completed this open-label trial. There was significant and robust resolution of symptoms of all effectiveness measures, including the symptoms of anxiety, as shown by changes from baseline in HAM-A, ASRS-v1.1, and CGI at 8 weeks. Also there was significant reduction in the disability score at 12 weeks. Patients tolerated the treatment, and there were no significant cardiovascular changes at 12 weeks. There was decrease in mean weight at 12 weeks by 2.2 kg (P < .001). Mixed amphetamine salts MAS-XR can be used in adult patients with ADHD and comorbid anxiety symptoms. Larger controlled studies are needed to support the effectiveness of mixed amphetamine salts in patients with comorbid anxiety symptoms. Treatments need to include the targeting of the ADHD symptoms effectively in order to achieve better resolution of anxiety symptoms.

We previously reported that treatment of prepubertal male rats with low, injected or oral, doses of methylphenidate stimulated cfos, fosB and arc expression in many areas of the developing brain. In the present study our objective was to determine whether the widely prescribed psychostimulant Adderall XR (ADD) exerted similar effects in infantile and prepubertal rat brain. We report here, for the first time, that low threshold doses of oral ADD, an extended-release mixture of amphetamine salts, now routinely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), also increased cfos expression in infantile (postnatal day 10; PD10) and prepubertal (PD24) rat brain. These threshold doses were correlated with blood levels of amphetamine determined by liquid chromatography-mass spectrometry. Moreover, we observed that chronic treatment with oral ADD (1.6 mg/kg; x 14 days) not only significantly down-regulated cfos expression following a final challenge dose of ADD in prepubertal (PD24) rat striatum and cortex, quantified in terms of FOS immunoreactivity (FOS-ir), but did so at a daily dose that was without effect with methylphenidate (MPH); that is a much higher oral dose of MPH (7.5 mg/kg; x 14 days) failed to induce down-regulation of cfos expression. Similar experiments in infantile rats (PD10), but using a threshold injected dose of ADD (1.25 mg/kg sc) also significantly reduced striatal and cingulate cortical FOS-ir. An additional finding in the prepubertal rats was that oral ADD-induced FOS-ir was observed in the cerebral cortex following doses lower than the threshold dose necessary to increase FOS-ir in the striatum. This was not the case in the PD10 rats. In conclusion, our efforts to calibrate biological responses, such as immediate early gene expression, to clinically relevant blood levels of stimulants confirmed that expression of cfos is very sensitive to repeated low doses of Adderall XR. It is now feasible to examine whether other genes are also affected in these young rats and if the changes we report are reversible. The implications of such studies should be relevant to the putative effects of psychostimulant treatment of very young children.

Adderall, consisting of a mixture of amphetamine salts and dextroamphetamine salts, is a prescription drug for attention deficit/hyperactivity disorder (ADHD) and narcolepsy. Labeled or unlabeled use of Adderall is gaining popularity among young children and college students. Although it is rare, Adderall use is associated with myocardial infarction and even sudden death. We report a case of a young man with acute myocardial infarction after taking 2 15-mg tablets of Adderall XR with alcohol and discuss the clinical features, diagnosis, and management of the cardiovascular effect of amphetamine-containing drugs.

Attention-deficit/hyperactivity disorder (ADHD) is a common disorder among adolescents but can be a challenge to diagnose in this population for several reasons. Obvious symptoms of hyperactivity and impulsivity are displayed less frequently than in younger children. Direct observation by potential raters is more limited because adolescents spend less time with parents and usually have multiple teachers throughout the day. Also, adolescents often suffer from psychiatric comorbidities, which affect the presentation of ADHD and can confound the diagnosis. Similarly, impaired social skills and academic performance may result from this disorder or for other reasons. These difficulties underscore the importance of a careful and comprehensive assessment that includes parent-, teacher-, and self-reported measures of functioning in several environments, including school, home, and work. Because ADHD is chronic and usually impairing in several domains (eg, social skills, academic performance, family relations, emotional health, driving), adequate treatment is essential. However, there are relatively few treatment studies in adolescents. Stimulant agents are well established as first-line medication treatment for both school-aged children and adults. Existing data support that this is also the case with adolescents. Specifically, both an extended-release formulation of methylphenidate, osmotic-release oral system (OROS MPH; CONCERTA) and a mixed amphetamine salts extended-release (MAS XR; Adderall XR) have demonstrated efficacy and safety in reducing the core symptoms of ADHD in well-designed, multisite, placebo-controlled, double-blind trials. Additional research is needed to further refine diagnostic and assessment tools in the adolescent population.

Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in educational, occupational, neuropsychological, and social functioning in adults. Successful diagnosis and treatment of the disorder in adults can be a challenge because recent and integrative clinical guidelines are lacking and diagnostic criteria are based on making a retrospective diagnosis of childhood-onset ADHD. To develop evidence-based recommendations for the treatment of ADHD in adults, the scientific literature was reviewed, including primary clinical studies, meta-analyses, and available clinical guidelines. Studies show that stimulant therapy is highly effective and safe in the management of ADHD in adults, with similar response rates to those reported in children at doses that are equivalent on a mg/kg basis. Long-acting stimulants, such as OROS methylphenidate (OROS MPH, Concerta), dexmethylphenidate (d-MPH, Focalin), and mixed amphetamine salts extended release (MAS XR, Adderall XR), have durations of action of up to 10 to 12 hours, which permit once-daily dosing. For adults with ADHD who do not respond to stimulant therapy or who have a comorbid condition in which a stimulant is contraindicated, the nonstimulant atomoxetine (Strattera) may be an appropriate alternative. For many adults, cognitive-behavioral therapy in addition to pharmacotherapy may improve treatment response. Attention-deficit/hyperactivity disorder medications may increase blood pressure and heart rate in adults, so patients should be monitored.

This study investigated whether OROS methylphenidate (OROS MPH, Concerta) or extended-release mixed amphetamine salts (se-AMPH ER, Adderall XR) were associated with worsening of driving performance, or drug rebound, relative to placebo 16-17 hours post-ingestion. Nineteen male adolescent drivers aged 17-19 with attention-deficit/hyperactivity disorder (ADHD) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH, 30 mg of se-AMPH ER, or placebo. Medication was taken at 08:00 in a randomized, double-blind, placebo-controlled, crossover study. Participants drove a simulator at 17:00, 20:00, 23:00, and 01:00, and drove their own cars over a 16-mile road course at 24:00. The main outcome measures were composite scores of driving performance. Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons. However, inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight (p = 0.04), suggesting possible rebound. During both late simulator and on-road testing, driving performance variance was approximately 300% greater during the se-AMPH ER compared to the OROS MPH condition.