Amphetamine Products Research Articles

Transdermal dextroamphetamine (Xelstrym) for ADHD.

The FDA has approved a dextroamphetamine transdermal patch (Xelstrym – Noven) for once-daily treatment of attention-deficit/hyperactivity disorder (ADHD) in patients ≥6 years old. Xelstrym is the first transdermal amphetamine product to be approved in the US. A methylphenidate transdermal patch (Daytrana, and generics) has been available for years for treatment of ADHD.

Acute Hyperkinetic Movement Disorders as a Multifactorial Pharmacodynamic Drug Interaction Between Methylphenidate and Risperidone in Children and Adolescents.

Acute hyperkinetic movement disorders have been reported with the concomitant use of attention-deficit/hyperactivity disorder (ADHD) stimulants and antipsychotics in children and adolescents. We analyzed postmarketing reports of suspected acute hyperkinetic movement disorder associated with concomitant use of ADHD stimulants and antipsychotics. We searched for postmarketing reports of acute hyperkinetic movement disorders associated with concomitant use of ADHD stimulants-antipsychotics in the US Food and Drug Administration Adverse Event Reporting System through December 6, 2019. PubMed and EMBASE were also searched for acute hyperkinetic movement reports with the concomitant use of ADHD stimulants-antipsychotics through January 13, 2020. We identified 36 cases resulting in acute hyperkinetic movement disorder associated with the concomitant use of ADHD stimulants-antipsychotics, 19 of which were also identified in the medical literature. From an ADHD stimulant perspective, methylphenidate products accounted for the largest number of cases (n = 23 [64%]), followed by amphetamine products (n = 9 [25%]) and atomoxetine (n = 4 [11%]). From an antipsychotic perspective, all 36 cases were reported with second-generation antipsychotics, particularly risperidone (n = 20 [56%]). Most of the cases were reported in boys (n = 31 [86%]) aged 6 to 12 years (n = 27 [75%]). Approximately 53% of the cases reported a time to onset within 24 hours of the drug change. Acute dystonic reactions (n = 27 [75%]) were the most frequently reported movement disorder. As outlined in changes to the US prescribing information for all methylphenidate and risperidone products, health care professionals should be aware that changes to this combination may be associated with a pharmacodynamic drug-drug interaction resulting in acute hyperkinetic movement disorder.

Retrospective suspect and non-target screening combined with similarity measures to prioritize MDMA and amphetamine synthesis markers in wastewater

3,4-Methylenedioxymethamphetamine (MDMA) and amphetamine are commonly used psychoactive stimulants. Illegal manufacture of these substances, mainly located in the Netherlands and Belgium, generates large amounts of chemical waste which is disposed in the environment or released in sewer systems. Retrospective analysis of high-resolution mass spectrometry (HRMS) data was implemented to detect synthesis markers of MDMA and amphetamine production in wastewater samples. Specifically, suspect and non-target screening, combined with a prioritization approach based on similarity measures between detected features and mass loads of MDMA and amphetamine was implemented. Two hundred and thirty-five 24 h-composite wastewater samples collected from a treatment plant in the Netherlands between 2016 and 2018 were analyzed by liquid chromatography coupled to high-resolution mass spectrometry. Samples were initially separated into two groups (i.e., baseline consumption versus dumping) based on daily loads of MDMA and amphetamine. Significance testing and fold-changes were used to find differences between features in the two groups. Then, associations between peak areas of all features and MDMA or amphetamine loads were investigated across the whole time series using various measures (Euclidian distance, Pearson's correlation coefficient, Spearman's rank correlation coefficient, distance correlation and maximum information coefficient). This unsupervised and unbiased approach was used for prioritization of features and allowed the selection of 28 presumed markers of production of MDMA and amphetamine. These markers could potentially be used to detect dumps in sewer systems, help in determining the synthesis route and track down the waste in the environment.

New research sounds alarm about increased stimulant use among U.S. adults

The number of adults using central nervous system (CNS) stimulants grew by approximately 80% over a 5-year period, according to new findings published in BMJ Open in August 2021. The total number of amphetamine and methylphenidate prescriptions dispensed grew even faster, with an increase of roughly 96%, according to the study results. “My message is this: It's time to start paying attention,” said lead author Thomas J. Moore from the Center for Drug Safety and Effectiveness at Johns Hopkins University Bloomberg School of Public Health. “The opioid epidemic continued for years before the medical and public health community realized action was needed. We need more research to understand this major trend and why it is happening.” Trends in CNS stimulant use that Moore and the research team found included a younger population of adults, as well as adults with higher education degrees who were more likely to be unmarried. “We need to know what is driving this increase, and why so much use is in combination with antidepressants and antianxiety drugs,” said Moore. The study results found that stimulant users frequently reported taking medications for a variety of mental, neurological, and developmental conditions: 77.8% indicated they took medication for ADHD, 26.8% reported taking anxiety medication, 25.1% said they had taken drugs for depression, and 15.3% indicated drug therapy for other mental or neurological conditions. Andrew Peterson, PharmD, PhD, FCPP, executive director of the Substance Use Disorder Institute at the University of the Sciences in Philadelphia, was not surprised by the results of the BMJ Open study. The trend for youths being diagnosed and treated for conditions such as ADHD with stimulant medications has been increasing since the early 2000s, according to CDC. “Therefore, as the youths became adults, the carry-over for using stimulants to treat these conditions may be a strong factor contributing to the increase seen,” said Peterson. “A particularly vulnerable group are college students who may be misusing these agents to improve cognitive ability and academic achievement.” In the BMJ Open study, Moore and the researchers wrote that the growing use of these stimulants should renew interest in updating, characterizing, and managing the risks of this drug class. For example, the larger numbers of younger age groups using CNS stimulants raises the question of whether or when these prescribed stimulants for ADHD in childhood or adolescence should be discontinued as the child grows older. Peterson encourages pharmacists to help counsel patients—youths and parents, as well as adults—about the risks associated with stimulant misuse. He said research should focus on how pharmacists can use evidence-based strategies such as Screening, Brief Intervention and Referral to Treatment (SBIRT) in the community setting to identify individuals at risk for misusing stimulants. But before this, pharmacists and other health care providers need to feel confident addressing substance use disorders with their patients, which includes understanding the prevalence, incidence, and consequences of stimulant use and misuse. “This appears to be a great opportunity for researching the pharmacist's role in providing this education,” Peterson said. While CNS stimulant use was more frequent in the youngest age cohort, according to the study findings, the largest percentage increases occurred in adults aged 25 years and older. Examined by sex, the largest rise occurred among females, with a 72% jump in CNS stimulant use over the 5-year period. “We saw big differences by age, race, and sex,” said Moore. “The growth was largest in younger, white, and female patients, smallest in minorities and older patients. Increase was much larger in amphetamines versus methylphenidate.” Amphetamine product use increased by roughly 119% over the 5-year period. Growth in methylphenidate products was slower with an estimated 39% increase during that time frame. The findings come from the annual U.S. Medical Expenditure Panel Survey, the largest annual health care survey sponsored by the federal government. Researchers analyzed annual surveys from 2013 through 2018 and looked at a random sample of approximately 30,000 individuals and 325,000 prescriptions each year.

Psychopharmacology of Pediatric Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder identified in 4% to 8% of children, adolescents, and adults. Features of ADHD found in childhood and adolescence persist into adulthood in as many as 70% of pediatric patients with this diagnosis. Various behavioral therapies are helpful for ADHD. This discussion focuses on medications that research has shown to be beneficial for treating the core features of this condition. Drugs that are approved by the US Food and Drug Administration for ADHD are psychostimulants (methylphenidate and amphetamine products), long-acting alpha-2 agonists (clonidine, guanfacine), and a selective norepinephrine reuptake inhibitor (atomoxetine). Clinicians prescribing these drugs should monitor their patients for both beneficial and adverse effects. Although it is often difficult to find a specific medication that is superior to others for all people with ADHD, research does show that methylpheni-date is typically superior to amphetamines. Thus, careful clinician scrutiny is needed to find the optimal formulation for those taking these medications. [ Psychiatr Ann . 2021;51(10):459–466.]

How Frequent Is Switching From an Initial Stimulant Family to the Alternative One in the Clinical Setting?: A Pilot Study of 49 Consecutively Referred Medication-Naive Adults With Attention-Deficit/Hyperactivity Disorder.

This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants. Subjects were 49 unmedicated adults (18-45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function-Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale-Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics. Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment ("strugglers") was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance. Forty-one percent of medication-naive adults with ADHD initiating stimulant treatment required a switch from the initially prescribed stimulant family to the alternative one because of poor tolerability. Switching could not be adequately predicted by baseline demographic or clinical characteristics. These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying a safe and effective treatment for these patients.

Use of Lisdexamfetamine or Amphetamine? Interpretation of Chiral Amphetamine Analyses.

Amphetamine is frequently detected in forensic toxicological cases. Differentiating between the two isomers of amphetamine (d-amphetamine and l-amphetamine) and determining their relative proportion are fundamental to correctly interpret the results of toxicological analyses. The aim of this study was to examine the profile of amphetamine as well as storage stability of the isomers in authentic samples from patients chronically treated with lisdexamfetamine (LDX), the most prescribed medical amphetamine product in Sweden. Blood and urine samples were collected from 18 patients. The samples were analyzed with an achiral (racemate) method for quantification of amphetamine and with a chiral method to determine the proportion of each isomer of amphetamine. The median daily dose of LDX was 40 mg (range, 20-70 mg). The median amphetamine concentration was 0.06 µg/g (range, 0.02-0.15 µg/g) in blood and 6 µg/mL (range, 1-22 µg/mL) in urine. Only d-amphetamine was found in the blood and urine samples from the included patients. Furthermore, no formation of l-amphetamine occurred during the storage for 3 months at 4°C, 9 months at -20°C and three freeze-thaw cycles. The results from this study may be helpful in the interpretation of whether the source of identified amphetamine in biological samples is from LDX drug intake or not.

Incidence of Heart Failure and Cardiomyopathy Following Initiation of Medications for Attention-Deficit/Hyperactivity Disorder: A Descriptive Study.

Stimulant abuse is associated with cardiomyopathy, but cardiomyopathy rates with therapeutic use of stimulants for attention-deficit/hyperactivity disorder (ADHD) are poorly characterized. Labels for methylphenidate, amphetamine, and atomoxetine caution against use in patients with cardiovascular disease. We sought to assess the incidence of new-onset heart failure or cardiomyopathy among initiators of these medications. Using the Sentinel distributed database, we analyzed new-onset heart failure or cardiomyopathy among initiators of selected ADHD medications (amphetamine products including lisdexamfetamine, methylphenidate, and atomoxetine), by duration of use (0-90, 91-180, 181-270, 271-365, 366-730, and 731-1095 days) and age group (<22, 22-44, 45-64, and ≥65 years). In our sample of 2,012,948 initiators of ADHD medications, 44.6% were female, and 54.1% were younger than 22 years. Heart failure/cardiomyopathy rates in the age groups younger than 22 and 22 to 44 years old were less than 50 per 10,000 person-years, without clear trends by duration of use. The highest rates occurred soon after treatment initiation in the age group 65 years or older, with 1 case per 10.5 person-years of follow-up, or 950 cases per 10,000 person-years, for days 0-90. Heart failure/cardiomyopathy rates were not higher over 3 years of ADHD medication use compared with shorter-term treatment. In older age groups, lower rates later in treatment could reflect depletion of patients predisposed to the outcome if they develop it soon after starting treatment.

Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

Objectives: To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study.Methods: Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10–20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs.Results: The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache.Conclusion: AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

Characterisation of aqueous waste produced during the clandestine production of amphetamine following the Leuckart route utilising solid‐phase extraction gas chromatography–mass spectrometry and capillary electrophoresis with contactless conductivity detection

Chemical waste from the clandestine production of amphetamine is of forensic and environmental importance due to its illegal nature which often leads to dumping into the environment. In this study, 27 aqueous amphetamine waste samples from controlled Leuckart reactions performed in Germany, the Netherlands, and Poland were characterised to increase knowledge about the chemical composition and physicochemical characteristics of such waste. Aqueous waste samples from different reaction steps were analysed to determine characteristic patterns which could be used for classification. Conductivity, pH, density, ionic load, and organic compounds were determined using different analytical methods. Conductivity values ranged from 1 to over 200 mS/cm, pH values from 0 to 14, and densities from 1.0 to 1.3g/cm3 . A capillary electrophoresis method with contactless conductivity detection (CE-C4 D) was developed and validated to quantify chloride, sulphate, formate, ammonium, and sodium ions which were the most abundant ions in the investigated waste samples. A solid-phase extraction sample preparation was used prior to gas chromatography-mass spectrometry analysis to determine the organic compounds. Using the characterisation data of the known samples, it was possible to assign 16 seized clandestine waste samples from an amphetamine production to the corresponding synthesis step. The data also allowed us to draw conclusions about the synthesis procedure and used chemicals. The presented data and methods could support forensic investigations by showing the probative value of synthesis waste when investigating the illegal production of amphetamine. It can also act as starting point to develop new approaches to tackle the problem of clandestine waste dumping.

Identification of specific markers for amphetamine synthesised from the pre-precursor APAAN following the Leuckart route and retrospective search for APAAN markers in profiling databases from Germany and the Netherlands.

α-Phenylacetoacetonitrile (APAAN) is one of the most important pre-precursors for amphetamine production in recent years. This assumption is based on seizure data but there is little analytical data available showing how much amphetamine really originated from APAAN. In this study, several syntheses of amphetamine following the Leuckart route were performed starting from different organic compounds including APAAN. The organic phases were analysed using gas chromatography-mass spectrometry (GC-MS) to search for signals caused by possible APAAN markers. Three compounds were discovered, isolated, and based on the performed syntheses it was found that they are highly specific for the use of APAAN. Using mass spectra, high resolution MS and nuclear magnetic resonance (NMR) data the compounds were characterised and identified as 2-phenyl-2-butenenitrile, 3-amino-2-phenyl-2-butenenitrile, and 4-amino-6-methyl-5-phenylpyrimidine. To investigate their significance, they were searched in data from seized amphetamine samples to determine to what extent they were present in illicitly produced amphetamine. Data of more than 580 cases from amphetamine profiling databases in Germany and the Netherlands were used for this purpose. These databases allowed analysis of the yearly occurrence of the markers going back to 2009. The markers revealed a trend that was in agreement with seizure reports and reflected an increasing use of APAAN from 2010 on. This paper presents experimental proof that APAAN is indeed the most important pre-precursor of amphetamine in recent years. It also illustrates how important it is to look for new ways to identify current trends in drug production since such trends can change within a few years.

New drugs and dosage forms

Amphetamine extended-release oral suspension (Adzenys ER, Neos Therapeutics): An orange-flavored, sorbitol-sweetened liquid formulation has been added to the product line. The suspension contains a 3:1 ratio of d-amphetamine to l-amphetamine and is not to be substituted milligram for milligram with other amphetamine products. The drug is a Schedule II controlled substance and subject to FDA Medication Guide requirements. Bevacizumab-awwb solution for i.v. infusion (Mvasi, Amgen): The biosimilar to bevacizumab, a vascular endothelial growth factor inhibitor, is indicated for use in combination with fluorouracil in the treatment of metastatic colorectal cancer; in combination with chemotherapy regimens containing fluoropyrimidine and irinotecan or fluoropyrimidine and oxaliplatin, for the treatment of metastatic colorectal cancer that has progressed after first-line bevacizumab therapy; in combination with carboplatin and paclitaxel, for the first-line treatment of unresectable, locally advanced nonsquamous non–small cell lung cancer that has recurred or metastasized; in combination with interferon alfa, for the treatment of metastatic renal cell carcinoma; in combination with regimens containing paclitaxel and cisplatin or paclitaxel and topotecan, in the treatment of cervical cancer that persists or has recurred or metastasized; and for treatment of progressive glioblastoma in adults who received prior therapy.

Forensic analysis of P2P derived amphetamine synthesis impurities: identification and characterization of indene by-products.

1-Phenyl-2-propanone (P2P) is an internationally monitored precursor that has become increasingly difficult for illicit amphetamine producers to source, which means that alternative routes to its preparation have become increasingly important. One such approach includes the hydrolysis of alpha-phenylacetoacetonitrile (APAAN) with sulfuric acid. Previously, we reported the identification of 4,6-dimethyl-3,5-diphenylpryid-2-one following implementation of hydrolysis conditions and it was proposed that this compound might serve as one route specific by-product in the APAAN to P2P conversion. This study continued to explore the presence of impurities formed during this conversion and expanded also into a second route of P2P synthesis starting from alpha-methylstyrene (AMS). All P2P products underwent the Leuckart procedure to probe the presence of P2P-related impurities that might have carried through to the final product. Two by-products associated with the APAAN hydrolysis route to P2P were identified as 2,3-diacetyl-2,3-diphenylsuccinonitrile (1) and 2-methyl-1-phenyl-1,3-dicarbonitrile-1H-indene (2), respectively. Two by-products associated with the AMS route to P2P and subsequent Leuckart reaction were 1,1,3-trimethyl-3-phenyl-2,3-dihydro-1H-indene (3) and 1-phenyl-N-(phenylethyl)propan-2-amine (4), respectively. The two indenes (2 and 3) identified in synthesized amphetamine originating from P2P suggested that it might be possible to differentiate between the two synthetic routes regarding the use of APAAN and AMS. Furthermore, the association of these compounds with amphetamine production appears to have been reported for the first time. The presence of compounds 1 - 4 in seized amphetamine samples and waste products could facilitate the suggestion whether APAAN or AMS were employed in the synthesis route to the P2P. Copyright © 2016 John Wiley & Sons, Ltd.

Treatment receipt and outcomes from a clinic employing the attention-deficit/hyperactivity disorder treatment guideline of the children's medication algorithm project.

Little is known about the pattern of service receipt and outcomes from clinics implementing best practice guidelines in child mental health. This study aimed to determine these variables for a clinic that implemented an attention-deficit/hyperactivity disorder (ADHD) treatment guideline proposed by the Children's Medication Algorithm Project (CMAP). Secondary analyses of medical record extracts were conducted for children who received treatment from 2007 to 2012 in a specialty clinic linked to a public children's hospital in Canada. Patterns of medication selection and dosing were compared with CMAP guidelines. Outcomes were based on parent and teacher ratings on the ADHD portion of the Multimodal Treatment Study for ADHD (MTA)- Swanson, Nolan, and Pelham, Version IV (SNAP-IV). Data were available for 132 children (ages 5-14), 81.8% of whom had no previous ADHD medication exposure, and 97.0% of whom had started at least one medication. Methylphenidate was used first for 59.8% of children, whereas 33.3% started with an amphetamine product. Of the 47.0% of children who progressed to a second medication trial, 88.7% tried a stimulant from a second class. In total, 19.7% tried atomoxetine, which was typically used as a third stage choice (i.e., after two different stimulant exposures). Stage four to six medications were rarely used, rather stimulants were retried after atomoxetine and/or medication combinations were tried. Symptomatic remission at the end of treatment was achieved by 70.4% and 82.4%, according to parents and teachers respectively, for those with outcome data and who completed treatment. Outcomes for those further along the treatment algorithm were similar to discharges at the beginning of the algorithm. The high rates of symptomatic remission observed within this clinical service may be a function of adherence to CMAP recommendations. However, the lack of a comparison group or experimental design prevents determination of causality. Additional investigations of the impacts of implementing evidence-based guidelines are critically needed, with proposed benchmarks to inform outcome evaluations.

A review of OROS methylphenidate (Concerta(®)) in the treatment of attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioural disorder with onset during childhood. It affects a child's development, both at home and at school, and impacts on social, emotional and cognitive functioning, in both the home and the school environment. Untreated ADHD is very often associated with poor academic achievement, low occupational status, increased risk of substance abuse and delinquency. Current practice guidelines recommend a multimodal approach in the treatment of ADHD, which includes educational, behavioural and mental health interventions, and pharmacological management. Stimulant medications, including methylphenidate (MPH) and amphetamine products, are recommended as first-line pharmacotherapy in the treatment of ADHD. The choice of stimulant is influenced by several factors; the most influential factor is the duration of action. Long-acting medication provides benefits long after school and work. It also increases the likelihood of once-daily dosing, thereby eliminating the need for mid-day dosing, making the treatment more private, avoiding stigma and improving adherence to medication. MPH is the most widely used psychotropic medication in child psychiatry. It was first developed for use in children as an oral, immediate-release formulation and more recently as various extended-release formulations. These latter formulations include the 12 h preparation Concerta(®) (osmotic-release oral system [OROS] MPH), which utilizes an osmotic pump system, designed to overcome the difficulties of multiple daily dosing. Since it received approval from the US Food and Drug Administration in August 2000, OROS MPH has been quickly and widely accepted as one of the preferred treatments for ADHD because of its once-daily dosing. This paper reviews the data in support of long-acting OROS MPH in children, adolescents and adults, both in ADHD and in association with its comorbidities.

An epidemiological study on substance abuse among college students of north India (Kashmir valley)

Background:-Substance abuse disorder is among the leading public health problems in modern day world as they cause enormous human suffering in terms of morbidity, mortality and economic loss; and threatens the very social fabric of almost all communities around the world and as such is a great threat to the global health, economy and peace. Like most social behaviors the etiology of substance abuse is complex, varying through time, geographical regions and by demographic characteristics. Among young people, students are the most vulnerable group as the initiation into substance abuse first starts during this period. Aims and Objectives:-To find out the prevalence and pattern of substance abuse and its association with various socio-cultural and demographic variables. Material & Methods: Multi-stage random sampling method was adopted to select the study subjects. The study subjects were asked about the substance abuse and related socio-demographic variables by means of WHO model core questionnaire format and results were subjected to statistical analysis. Results: The overall life-time prevalence of for substance abuse among college students was found to be 31.3%. Male students had significantly higher prevalence of substance abuse as compared to female counterparts(37.5% versus 19.6% respectively).The most common substance being abused was Tobacco products(22.5%) followed by solvents (10.0%), alcohol (6.2%), sedatives (5.9%), cannabis (4.4%), amphetamine products (2.1%), hallucinogens (0.5%) and cocaine (0.3%). Age, gender and family type were found to be strongly associated with substance abuse (p

Comparative &amp;lt;i&amp;gt;in Vitro&amp;lt;/i&amp;gt; Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

Use of new amphetamine-type stimulants (ATS) as designer drugs is a serious problem worldwide. ATS are used in tablet, capsule, and powder forms, and can be mixed with other drugs. There is little information available on how these new drugs are metabolized or their ability to inhibit the metabolism of co-administered drugs. This study aimed to investigate the metabolism of six 4-substituted analogs of methamphetamine (MA), and their potential inhibition of MA metabolism. The metabolism of MA and the 4-substituted MAs was examined in vitro using human metabolic enzymes. Metabolite analyses were performed using trifluoroacetyl derivatization and GC-MS. The experiments showed that cytochrome P450 2D6 (CYP2D6) was involved in the major metabolic pathway of MA, where it catalyzed N-demethylation of 4-fluoromethamphetamine (4-FMA), 4-chloromethamphetamine (4-CMA), 4-bromomethamphetamine (4-BMA), 4-iodomethamphetamine (4-IMA) and 4-nitromethamphetamine (4-NMA), and O-demethylation of 4-methoxymethamphetamine (4-MMA). The half maximal inhibitory concentration (IC50) values for CYP2D6 using MA as substrate were different for each of the 4-substituted MAs. The strongest inhibitors of amphetamine production from MA were, in order, 4-IMA, 4-BMA, 4-CMA, 4-MMA, 4-FMA, and 4-NMA. The same order was observed for the IC50 values for inhibition of p-hydroxymethamphetamine production from MA, except for the IC50 of 4-MMA. The IC50 values of 4-IMA were lower than the IC50 values of fluoxetine and higher than that of quinidine. The results of this study imply that the risk of illicit drug interactions fluctuates so widely that unintentional fatal drug poisonings could occur.

The Pharmacology and Clinical Outcomes of Amphetamines to Treat ADHD

Attention-deficit hyperactivity disorder (ADHD) treatment options include pharmacological and nonpharmacological approaches. In North America, psychostimulants (amphetamine and methylphenidate) are considered first-line pharmacological treatments for patients (children, adolescents and adults) with ADHD. However, in the UK, National Institute for Health and Clinical Excellence (NICE) guidelines have placed short-acting d-amphetamine as a third-line treatment option due to a lack of contemporary, published clinical trials on its efficacy and the concerns from clinical and patient experts regarding the potential for increased abuse and/or misuse compared with methylphenidate. These guidelines do not account for some of the more recent amphetamine products that have been developed to alleviate some of these concerns, but that are not currently approved in the UK or other European countries. The purpose of this review is to describe the pharmacology and clinical efficacy of various amphetamine compositions, as well as to explore the apparent differences in these compositions and their associated risks and benefits. A PubMed literature search was conducted to investigate amphetamine pharmacology, clinical efficacy and safety and ADHD outcomes in the published literature from 1980 through March 2011. Search terms included the keywords 'ADHD' or 'ADD' or 'hyperkinetic disorder' and any of the following keywords combined with 'or': 'amphetamine', 'dexamphetamine', 'mixed amphetamine salts', 'lisdexamfetamine' and 'methamphetamine'. The search included English-language primary research articles and review articles but excluded editorial articles and commentaries. The literature search resulted in 330 articles. Pertinent articles relating to amphetamine pharmacology, compositions, clinical efficacy and safety, effectiveness and tolerability, ADHD outcomes and abuse liability were included in this review. The different delivery profiles of amphetamine compositions result in pharmacological and pharmacokinetic differences that contribute to varying effects in the clinical treatment of ADHD, ADHD outcomes and abuse liability. The efficacy and safety of amphetamine compositions for the treatment of ADHD have been demonstrated in clinical trials and meta-analyses, and the long-acting amphetamine compositions have been widely studied and found efficacious without increased adverse effects. Long-acting amphetamine compositions offer the obvious advantage of enhanced duration of action over short-acting amphetamine compositions, and lisdexamfetamine has been shown to have reduced abuse liability compared with short-acting amphetamine.

Treatment of ADHD in patients unresponsive to methylphenidate

R.B. is an 8-year-old boy with a history of attention-deficit/hyperactivity disorder (ADHD) that was first diagnosed at age 4 years. When he was referred at age 8, he was in grade 3 but failing most of his subjects. He was also found to have oppositional defiant disorder at home and at school and, despite normal intelligence, a substantial learning disability in expressive and receptive language. R.B. first started stimulant medication at 5 years old: 5, 10 and finally 20 mg of methylphenidate taken in the morning and again at noon. The medication did not greatly alleviate symptoms; poor compliance (many doses at school were forgotten or missed) and poor coverage between doses were thought to be the reasons for the poor medication response. The child then started long-lasting OROS methylphenidate. The hope was that the once-per-day formulation, reported to last 10–12 hours, would improve compliance since no medication needed to be taken at school and would provide better coverage. Since the child was already on 40 mg of methylphenidate per day, the OROS methylphenidate was started at 36 mg per day and then increased to 54 mg per day (a high dose for a 6-year-old). Despite the high dose in the morning, the child continued to have a short attention span with disruptive, impulsive and oppositional behaviour at school. In the late afternoon and early evening, he became very emotional, with frequent crying, marked irritability and many tantrums. In light of the poor response and the side effects to high dosages of OROS methylphenidate in grade 1, the child was switched to atomoxetine (a non-stimulant) in grade 2. This medication was increased from 0.5 mg/kg to 0.8 mg/kg, 1.2 mg/kg and then 1.4 mg/ kg. The emotional side effects of the OROS methylphenidate subsided, but the clinical effects of the atomoxetine in controlling ADHD symptoms were not great. To achieve better symptom control, small dosages of short-acting methylphenidate were added, initially at 10 mg, and quickly raised to 20 mg in the morning and at noon. Despite maximum dosages of atomoxetine combined with a fairly high dosage of methylphenidate, R.B. continued to have attentional, behavioural and learning problems at school and at home. He was referred to a special day program at the beginning of grade 3 and was gradually taken off all medications. As part of the day program, a behavioural program combined with parent training was begun for his oppositional behaviour, and special tutoring and remediation in language arts was begun for his learning disabilities. He also started a long-acting mixed amphetamine salt product (Adderall XR), initially at 10 mg per day and increased to 15 and then 20 mg per day. The combination of Adderall XR at 20 mg per day, academic remediation and behavioural therapy proved effective, and he was gradually reintegrated into his regular classroom where he continues to do well. This case illustrates several important issues. First, children with ADHD often have other comorbid conditions (e.g., 40% may have oppositional defiant disorder and 20% may have specific learning disabilities) that need to be addressed and treated, as stimulant medication is not likely to correct everything. Second, although many individuals (45%) respond equally well to methylphenidate or amphetamine products, some (28%) respond preferentially to methylphenidate whereas others (17%) respond preferentially to amphetamines and about 10% respond to neither group of stimulants.1 It is still unclear what predicts preferential response to one or the other stimulant. This preferential response should be kept in mind, so when children don’t respond well to methylphenidate, the first change in medication should be to amphetamines. Had R.B. been tried on amphetamines earlier and had other needed interventions (e.g., academic remediation in the language arts, parent training, behavioural program) been established earlier, his problems may have been improved in grade 1 rather than grade 3.

Understanding the Effect Size of Lisdexamfetamine Dimesylate for Treating ADHD in Children and Adults

Objective: An earlier meta-analysis of pediatric clinical trials indicated that lisdexamfetamine dimesylate (LDX) had a greater effect size than other stimulant medications. This work tested the hypothesis that the apparent increased efficacy was artifactual. Method: The authors assessed two potential artifacts: an unusually high precision of measurement and an unusually low placebo effect. The authors evaluated generalizability from children of adults. Results: The LDX effect sizes for children were significantly larger than the pooled stimulant effect sizes from studies using the same outcome measures. However, although no other individual stimulant study had an effect size greater than LDX, there was overlap between the 95% confidence intervals for some of these studies and the LDX study. The high LDX effect sizes were not due measurement or placebo effect artifacts. LDX effect sizes for adults were not larger than the stimulant effect sizes from other studies. Conclusion: The high LDX effect size for children could not attributed to measurement artifacts. The superiority of LDX in the pediatric clinical trial reflected the greater efficacy of amphetamine products, compared with methylphenidate products but required replication in children because (a) the results were based on only one trial of LDX in children, and (b) the finding did not generalize to adults.