lisdexamfetamine-dimesylate and Substance-Related-Disorders

Agonist-based pharmacologic intervention is an accepted approach in treatment of opioid and tobacco use disorders.. We conducted a systematic review and meta-analysis to evaluate usefulness of an agonist approach as treatment of (psycho)stimulant use disorder (PSUD).. We reviewed PubMed/Medline, LILACS, and ClinicalTrials.gov databases searching for randomized, double-blind, placebo-controlled, parallel-design studies evaluating outcomes of individuals treated for cocaine- or amphetamine-type substance use disorder. We combined results of all trials that included the following prescription psychostimulants (PPs): modafinil, methylphenidate, or amphetamines (mixed amphetamine salts, lisdexamphetamine, and dextroamphetamine). The combined sample consisted of 2889 patients. Outcomes of interest included the following: drug abstinence (defined as 2-3 weeks of sustained abstinence and the average maximum days of consecutive abstinence), percentage of drug-negative urine tests across trial, and retention in treatment. We conducted random-effects meta-analyses and assessed quality of evidence using the GRADE system.. Thirty-eight trials were included. Treatment with PPs increases rates of sustained abstinence [risk ratio (RR) = 1.45, 95% confidence interval (CI) = (1.10, 1.92)] and duration of abstinence [mean difference (MD) = 3.34, 95% CI = (1.06, 5.62)] in patients with PSUD, particularly those with cocaine use disorder (very low-quality evidence). Prescription amphetamines were particularly efficacious in promoting sustained abstinence in patients with cocaine use disorder [RR = 2.44, 95% CI = (1.66, 3.58)], and higher doses of PPs were particularly efficacious for treatment of cocaine use disorder [RR = 1.95, 95% CI = (1.38, 2.77)] (moderate-quality evidence). Treatment with prescription amphetamines also yielded more cocaine-negative urines [MD = 8.37%, 95% CI = (3.75, 12.98)]. There was no effect of PPs on the retention in treatment.. Prescription psychostimulants, particularly prescription amphetamines given in robust doses, have a clinically significant beneficial effect to promote abstinence in the treatment of individuals with PSUD, specifically the population with cocaine use disorder.

Topics: Amphetamine; Central Nervous System Stimulants; Cocaine; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Modafinil; Prescription Drugs; Randomized Controlled Trials as Topic; Substance-Related Disorders; Treatment Outcome

Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic.. Three databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles.. We identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol.. The numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Alcohol Drinking; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Drug Interactions; Humans; Illicit Drugs; Lisdexamfetamine Dimesylate; Methylphenidate; Substance-Related Disorders

Medication is an important element of therapeutic strategies for ADHD. While medications for ADHD are generally well-tolerated, there are common, although less severe, as well as rare but severe adverse events AEs during treatment with ADHD drugs. The aim of this review is to provide evidence- and expert-based guidance concerning the management of (AEs) with medications for ADHD.. For ease of use by practitioners and clinicians, the article is organized in a simple question and answer format regarding the prevalence and management of the most common AEs. Answers were based on empirical evidence from studies (preferably meta-analyses or systematic reviews) retrieved in PubMed, Ovid, EMBASE and Web of Knowledge through 30 June 2012. When no empirical evidence was available, expert consensus of the members of the European ADHD Guidelines Group is provided. The evidence-level of the management recommendations was based on the SIGN grading system.. The review covers monitoring and management strategies of loss of appetite and growth delay, cardiovascular risks, sleep disturbance, tics, substance misuse/abuse, seizures, suicidal thoughts/behaviours and psychotic symptoms.. Most AEs during treatment with drugs for ADHD are manageable and most of the times it is not necessary to stop medication, so that patients with ADHD may continue to benefit from the effectiveness of pharmacological treatment.

Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Body Size; Cardiovascular Diseases; Central Nervous System Stimulants; Child; Clonidine; Dextroamphetamine; Growth Disorders; Guanfacine; Heart Rate; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Propylamines; Psychoses, Substance-Induced; Seizures; Sleep Wake Disorders; Substance-Related Disorders; Suicide Prevention; Tic Disorders; Treatment Outcome

Lisdexamfetamine dimesylate (LDX) is a once-daily medication approved by the US Food and Drug Administration for the management of attention-deficit/hyperactivity disorder (ADHD) in children (aged 6-12 years) and adults.. This article reviews the pharmacologic and pharmacokinetic properties, clinical efficacy, and safety profile of LDX.. Studies, abstracts, reviews, and consensus statements published in English were identified through computerized searches of MEDLINE (1966-August 2008) and International Pharmaceutical Abstracts (1977-August 2008) using search headings lisdexamfetamine dimesylate, attention-deficit/hyperactivity disorder, NRP 104, NRP104-201, NRP104-301, NRP104-302, NRP104-303, and stimulant. Selected information provided by the manufacturer of LDX was included, as were all pertinent clinical trials. The reference lists of identified articles were also searched for pertinent information. Relevant abstracts presented at annual professional meetings were included as well.. Several studies have evaluated the pharmacokinetics of LDX in pediatric patients (6-12 years of age) and healthy adults with ADHD. LDX, a prodrug that is therapeutically inactive until metabolized in the body to dextroamphetamine (d-amphetamine), follows linear pharmacokinetics at therapeutic doses (30-70 mg). The efficacy of LDX in the treatment of ADHD was established on the basis of 1 long-term and 2 short-term controlled clinical trials in children who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for ADHD (either the combined or the hyperactive-impulsive subtype) and in 1 clinical trial with adults with ADHD. The efficacy trials in children found significant improvements in scores on the Swanson, Kotkin, Agler, M-Flynn, and Pelham deportment sub-scales, the Permanent Product Measure of Performance (Attempted and Correct), and the ADHD Rating Scale Version IV (ADHD-RS-IV) compared with placebo (all, P < 0.001). In the clinical studies designed to measure duration of effect, LDX, compared with placebo, provided efficacy for a full treatment day, up through and including 6 PM, based on parent ratings (Conners' Parent Rating Scale-Revised Short Form) in the morning, afternoon, and early evening (all, P < 0.001). Data from a long-term, open-label extension study that assessed the safety, tolerability, and efficacy of LDX for up to 12 months found LDX treatment resulted in significant improvement (>60%) from baseline in the ADHD-RS-IV at end point (P < 0.001), with good tolerability. The trial in adults found significant improvements in ADHD-RS scores at end point in patients receiving LDX (30,50, and 70 mg) (P < 0.001 for all active doses); significant improvements in ADHD-RS (using adult prompts) scores were observed at each postbaseline weekly assessment, with improvements noted within the first week in all active treatment arms. Results from human abuse liability studies noted that LDX had lower abuse-related drug-liking scores compared with immediate-release d-amphetamine at equivalent doses. The most common adverse events reported with LDX were typical of amphetamine products and included decreased appetite, insomnia, upper abdominal pain, headache, irritability, weight loss, and nausea.. Current evidence supports the efficacy and tolerability of LDX as a treatment option for the management of children (aged 6-12 years) and adults with ADHD. As such, LDX may be an integral part of a total treatment program for ADHD that can include other measures such as psychological, educational, and social interventions.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Substance-Related Disorders

This article reviews the unique prodrug stimulant lisdexamfetamine dimesylate (LDX, Vyvanse), an approved treatment for attention-deficit/hyperactivity disorder. LDX is an inactive prodrug in which l-lysine is chemically bonded to d-amphetamine. Although its efficacy is not significantly different from that of other stimulants, LDX may be different with respect to potential toxicity and abuse liability. In this article, I will review the short-term controlled studies that were the basis for LDX's approval for both children and adults; the lack of and need for more long-term studies; two double-blind, placebo-controlled, crossover studies that examined LDX's abuse liability; and clinical uses for the drug. The clinical implications stemming from LDX's unique characteristics are also discussed.

Topics: Attention Deficit Disorder with Hyperactivity; Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Drug Administration Schedule; Humans; Lisdexamfetamine Dimesylate; Nurse's Role; Placebos; Prodrugs; Psychiatric Nursing; Substance-Related Disorders; Treatment Outcome

This article introduces a ?younger at-risk sibling? design to study progression from other psychopathologies to their substance use disorder (SUD) complications. The design selects not-yet-SUD adolescents with high-risk-for-SUD psychopathology only if an older sibling has SUD. This "proof of concept' pilot study examines the design?s feasibility if the younger sibling has attention deficit hyperactivity disorder (ADHD).. Subjects were recruited from families at substance abuse treatment centers that had a non-SUD younger child with ADHD, from families at behavior disorder clinics that had a younger child with ADHD and SUD older child, and through general advertisements. Subjects were seen weekly for at least 3 months and monthly thereafter for 3 months. All were treated with open-label lisdexamfetamine dimesylate 30-70 mg per day. Outcomes explored were recruitment, compliance, diversion, ADHD improvement, and substance use interest.. 25 families were screened, 13 evaluated, and 8 began medication. ADHD Rating Scale-IV scores obtained by parent?adolescent consensus improved as expected with a stimulant. Rating forms could quantify substance use interest in subjects with some drug culture exposure but encountered a floor effect in those without. The design's complexity and implicit commentary on family dynamics complicated recruitment but may have facilitated retention.. Sibling pairs in which the older sibling has substance use and the younger sibling has ADHD exist. Such younger siblings can be recruited into a treatment study. The design may shed light on the pathogenesis and prevention of SUD complications from ADHD and theoretically other SUD comorbidities.

Topics: Adolescent; Adolescent Behavior; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Diagnosis, Dual (Psychiatry); Female; Humans; Lisdexamfetamine Dimesylate; Male; Medication Adherence; Pilot Projects; Research Design; Risk Factors; Siblings; Substance-Related Disorders

The objective of this study is to determine the safety, tolerability and abuse liability of single intravenous (i.v.) doses of lisdexamfetamine dimesylate (LDX) and immediate-release d-amphetamine sulphate in adult stimulant abusers compared with placebo. Adult substance abusers were enrolled in this phase I, randomized, single-centre, double-blind study. An initial cohort of three subjects was enrolled to assess safety followed by a primary cohort that consisted of nine subjects. Single i.v. doses of LDX (25 or 50 mg), immediate-release d-amphetamine sulphate (10 or 20 mg) or placebo were administered at a minimum of 48-h intervals in a single-dose, three-way crossover design. 20 mg of d-amphetamine showed significantly increased abuse-related liking scores compared with placebo (P < 0.05), whereas the liking effects of 50 mg LDX did not significantly differ from placebo. The mean C(max) of d-amphetamine was 38.9 +/- 8.1 and 105 +/- 91.4 ng/ml after the administration of 50 mg LDX and 20 mg d-amphetamine respectively. The mean T(max) of d-amphetamine was 2.51 h after the administration of 50 mg LDX and 0.82 h after the administration of 20 mg d-amphetamine. LDX was well tolerated in this population. In contrast to d-amphetamine, LDX administered intravenously did not produce significant subjective abuse-related liking scores at assessed doses.

Topics: Central Nervous System Stimulants; Dextroamphetamine; Double-Blind Method; Humans; Injections, Intravenous; Lisdexamfetamine Dimesylate; Male; Middle Aged; Prodrugs; Substance-Related Disorders

Lisdexamfetamine dimesylate (LDX) is the first prodrug stimulant and is indicated for the treatment of attention-deficit/hyperactivity disorder. A single-centre, double-blind, randomised, placebo-controlled, 6-period crossover study evaluated the abuse potential of single oral doses of 50, 100 (equivalent to 40 mg d-amphetamine), and 150 mg LDX, 40 mg d-amphetamine and 200 mg diethylpropion in 36 individuals with a history of stimulant abuse. On the primary abuse liability measure, maximum change of the Drug Rating Questionnaire-Subject Liking Scale compared with placebo, d-amphetamine and diethylpropion showed significant differences of 4.5 and 4.0 units, respectively (P < 0.001 for both vs placebo). LDX, administered at 50, 100 and 150 mg, showed nonsignificant differences of 2.0 and 2.1 units, respectively, at the two lower doses but a significant (P < 0.001 vs placebo) difference of 6.1 units at the highest dose. Subjects significantly favoured d-amphetamine 40 mg versus LDX 100 mg (2.4 units difference; P < 0.05). There was no significant difference in liking scores between d-amphetamine 40 mg and LDX 150 mg. Drug Rating Questionnaire-Subject Feel-Drug-Effect score was significantly lower for 100 mg LDX than for 40 mg d-amphetamine. There were no statistically significant differences between LDX and diethylpropion hydrochloride, a Schedule IV amphetamine-like stimulant, on abuse-related liking scores. Cardiovascular responses of LDX and d-amphetamine were similar at equivalent doses. In conclusion, at an equivalent amount of amphetamine base taken orally, LDX 100 mg had attenuated responses on measures of abuse liability compared with immediate-release d-amphetamine 40 mg. Abuse-related liking scores of LDX at a dose corresponding to a 50% higher amphetamine base (LDX 150 mg) were similar to d-amphetamine 40 mg.

Topics: Administration, Oral; Adult; Blood Pressure; Central Nervous System Stimulants; Dextroamphetamine; Diethylpropion; Female; Heart Rate; Humans; Lisdexamfetamine Dimesylate; Male; Prodrugs; Substance-Related Disorders

There are growing concerns about nonmedical use of ADHD stimulants among adolescents; yet, little is known whether there exist heterogeneous subgroups among adolescents with nonmedical ADHD stimulant use according to their concurrent substance use.. We used latent class analysis (LCA) to examine patterns of past-year problematic substance use (meeting any criteria for abuse or dependence) in a sample of 2203 adolescent participants from the National Surveys on Drug Use and Health 2006-2011 who reported past-year nonmedical use of ADHD stimulants. Multivariable latent regression was used to assess the association of socio-demographic characteristics, mental health and behavioral problems with the latent classes.. The model fit indices favored a four-class model, including a large class with frequent concurrent use of alcohol and marijuana (Alcohol/marijuana class; 41.2%), a second large class with infrequent use of other substances (Low substance class, 36.3%), a third class characterized by more frequent misuse of prescription drugs as well as other substances (Prescription drug+class; 14.8%), and finally a class characterized by problematic use of multiple substances (Multiple substance class; 7.7%). Compared with individuals in Low substance class, those in the other three classes were all more likely to report mental health problems, deviant behaviors and substance abuse service use.. Adolescent nonmedical ADHD stimulants users are a heterogeneous group with distinct classes with regard to concurrent substance use, mental health and behavioral problems. The findings have implications for planning of tailored prevention and treatment programs to curb stimulant use for this age group.

Topics: Adolescent; Amphetamines; Analgesics, Opioid; Central Nervous System Stimulants; Child; Cocaine-Related Disorders; Dextroamphetamine; Female; Hallucinogens; Heroin Dependence; Humans; Hypnotics and Sedatives; Inhalant Abuse; Lisdexamfetamine Dimesylate; Male; Marijuana Smoking; Methylphenidate; Multivariate Analysis; Pemoline; Prescription Drug Misuse; Regression Analysis; Substance-Related Disorders; Underage Drinking; United States

Psychostimulants (methylphenidate and amphetamines) are the drugs of first choice in the pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD).. We summarize the pharmacological characteristics of amphetamines and compare them with methylphenidate, special emphasis being given to a comparison of effects and side effects of the two substances. Finally, we analyze the abuse and addiction risks.. Publications were chosen based on a Medline analysis for controlled studies and meta-analyses published between 1980 and 2011; keywords were amphetamine, amphetamine salts, lisdexamphetamine, controlled studies, and metaanalyses.. Amphetamines generally exhibit some pharmacologic similarities with methylphenidate. However, besides inhibiting dopamine reuptake amphetamines also cause the release of monoamines. Moreover, plasma half-life is significantly prolonged. The clinical efficacy and tolerability of amphetamines is comparable to methylphenidate. Amphetamines can therefore be used if the individual response to methylphenidate or tolerability is insufficient before switching to a nonstimulant substance, thus improving the total response rate to psychostimulant treatment. Because of the high abuse potential of amphetamines, especially in adults, the prodrug lisdexamphetamine (Vyvanse) could become an effective treatment alternative. Available study data suggest a combination of high clinical effect size with a beneficial pharmacokinetic profile and a reduced abuse risk.. In addition to methylphenidate, amphetamines serve as important complements in the psychostimulant treatment of ADHD. Future studies should focus on a differential comparison of the two substances with regard to their effects on different core symptom constellations and the presence of various comorbidities.

Topics: Adolescent; Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Child; Controlled Clinical Trials as Topic; Dextroamphetamine; Half-Life; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Risk Factors; Substance-Related Disorders

The development and implementation of programs in the U.S. to minimize risks and assess unintended consequences of new medications has been increasingly required by the Food and Drug Administration (FDA) since the mid 1990s. This paper provides four case histories of risk management and post-marketing surveillance programs utilized recently to address problems associated with possible abuse, dependence and diversion. The pharmaceutical sponsors of each of these drugs were invited to present their programs and followed a similar template for their summaries that are included in this article. The drugs and presenting companies were OxyContin, an analgesic marketed by Purdue Pharma L.P., Daytrana and Vyvanse, ADHD medications marketed by Shire Pharmaceuticals, Xyrem for narcolepsy marketed by Jazz Pharmaceuticals, and Subutex and Suboxone for opioid dependence marketed by Reckitt Benckiser Pharmaceuticals Inc. These case histories and subsequent discussions provide invaluable real-world examples and illustrate both the promise of risk management programs in providing a path to market and/or for keeping on the market drugs with serious potential risks. They also illustrate the limitations of such programs in actually controlling unintended consequences, as well as the challenge of finding the right balance of reducing risks without posing undue barriers to patient access. These experiences are highly relevant as the FDA increasingly requires pharmaceutical sponsors to develop and implement the more formalized and enforceable versions of the risk management term Risk Evaluation and Mitigation Strategies (REMS).

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dextroamphetamine; Drug and Narcotic Control; Drug Industry; History, 20th Century; History, 21st Century; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Naloxone; Oxycodone; Product Surveillance, Postmarketing; Risk Management; Sodium Oxybate; Substance-Related Disorders

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dopamine; Drug Approval; Humans; Lisdexamfetamine Dimesylate; Norepinephrine; Prodrugs; Randomized Controlled Trials as Topic; Substance-Related Disorders; United States; United States Food and Drug Administration

Attention-deficit/hyperactivity disorder (ADHD) is known to be a strong risk factor for substance use disorders (SUD) in adolescence and in adulthood. Research shows that stimulant treatment does not increase the risk of SUD in adolescents or adults with ADHD but rather that stimulant treatments may have a protective effect. However, 2 in 10 youths with ADHD misuse their medication. Recent evidence suggests that slow uptake of medication in the brain allows for effective treatment without patients experiencing the euphoric qualities of immediate-release agents that lead to abuse or diversion. As a result, extended-release products and different formulations, such as lisdexamfetamine dimesylate (LDX), are less likely to be misused and diverted and may have lower abuse potential.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Delayed-Action Preparations; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Psychotropic Drugs; Risk Factors; Substance-Related Disorders; Time Factors