Lisdexamfetamine Research Articles

Normalizing the Neural Correlates of Binge-Eating Disorder with Lisdexamfetamine: A Case Report and Literature Review

The brain regions associated with binge-eating disorder (BED) and those targeted by Lisdexamfetamine (LDX) overlap. The present paper reviews the psychobehavioural and neuropharmacological mechanisms at play in BED and compulsive eating behaviours, along with the mechanisms of action LDX is thought to play. We present one case of chronic BED and highlight the EEG scans pre- and post-LDX treatment. The normalization of the patient’s electroencephalogy (EEG) activity associated with BED after LDX supports theorized mechanisms of LDX action, further explaining its efficacy in treatment. A significant decrease in theta band power was observed in the patient after treatment with LDX. Specifically, this decrease was modulated by changes in the F8 electrode corresponding to the orbitofrontal cortex (OFC)—An area associated with deficits in inhibitory function, seen in addictions and BED. A better understanding of the psychobehavioural and neuropharmacological mechanisms involved in BED and LDX treatment has the potential to significantly enhance our knowledge of the underlying pathogenesis, potential prevention, and optimal treatment options for patients.

Photodegradation kinetics of lisdexamfetamine dimesylate and structure elucidation of its degradation products by LC-ESI-QTOF

Herein, we investigate the photodegradation of lisdexamfetamine (LDX) in an aqueous solution.

A case series involving young children presenting with accidental ingestion of amphetamine based stimulants

•Attention Deficity Hyperactivity Disorder (ADHD) affects adults and children.•Stimulant prescribing for ADHD is increasing.•Overdose of amphetamine based stimulants results in a sympathomimetic toxidrome.•Lisdexamfetamine dimesylate is the first prodrug stimulant developed to treat ADHD.

Phentolamine for Treatment of Lisdexamfetamine Toxicity with Delayed Stimulant Effects

Phentolamine for Treatment of Lisdexamfetamine Toxicity with Delayed Stimulant Effects

Risk of relapse to binge eating disorder lower for lisdexamfetamine compared with placebo

Patients with binge eating disorder (BED) who were randomized to lisdexamfetamine dimesylate after initial response to the drug in an open‐label trial had a significantly lower risk of relapse than patients randomized to placebo, a study has found. Most adverse effects from lisdexamfetamine were mild to moderate in severity and were in line with the drug's safety profile from prior BED studies and from trials in treating attention‐deficit hyperactivity disorder (ADHD), the researchers reported.

Efficacy and Tolerability of Different Interventions in Children and Adolescents with Attention Deficit Hyperactivity Disorder.

Our study is an analysis of multiple publications involving assessing the comparable efficacy and tolerability of six interventions, which are lisdexamfetamine dimesylate (LDX), atomoxetine (ATX), methylphenidate (MPH), clonidine hydrochloride (CLON), guanfacine extended release (GXR), and bupropion, for young patients (6-18 years old) suffering from attention deficit hyperactivity disorder (ADHD). A conventional meta-analysis (MA) was performed to give direct comparisons and a network meta-analysis (NMA) was used to show the combination of direct and indirect evidence. Ranking preference for all the interventions under a certain outcome was given by the surface of cumulative ranking curve area (SUCRA). Overall, 15,025 participants from 73 studies were involved in our analysis. In the pairwise MA, LDX was associated with less withdrawal than ATX for lack of efficacy. MPH showed less effectiveness than LDX according to ADHD Rating Scale score. Based on the analysis of our NMA, significant results of efficacy that LDX is a competitive drug were observed when evaluating LDX in comparison with other drugs except for CLON. ATX and GXR presented higher rates of abdominal pain morbidity versus inactive treatment. The stimulants LDX and MPH are still highly recommended because they are highly effective and are tolerated well by patients. Among the non-stimulants, CLON can be taken into consideration for its appreciable effectiveness and tolerability. ATX and GXR can be seen as moderate choices.

Lisdexamfetamine: A Review in Binge Eating Disorder

Oral lisdexamfetamine dimesylate (Vyvanse®; lisdexamfetamine), a prodrug of dextroamfetamine, is currently the only drug to be approved in the USA for the treatment of moderate to severe binge eating disorder (BED) in adult patients. Its approval was based on the results of two pivotal short-term (12weeks) phase III studies, which showed a significantly greater reduction in binge eating days/week at the end of the study with lisdexamfetamine 50-70mg/day than with placebo. The findings of these studies have been supported and extended by the results of longer-term (≤52weeks) phase III studies, including one with a randomized 26-week withdrawal phase, which showed that lisdexamfetamine markedly reduced the risk of BED relapse relative to placebo. Lisdexamfetamine was generally well tolerated in clinical trials in patients with moderate to severe BED, with a tolerability profile similar to that observed in ADHD patients; most treatment-emergent adverse events (TEAEs) were of mild or moderate intensity. The most common TEAEs in phase III trials included dry mouth, headache and insomnia; TEAEs infrequently led to study drug discontinuation. In conclusion, lisdexamfetamine 50-70mg/day is an effective and generally well tolerated option for treating moderate to severe BED in adults.

Lisdexanfetamina em transtornos de humor: uma revisão sistemática

The present study is a systematic review of the literature published in the MEDLINE database to evaluate the effects and safety profile of lisdexamfetamine (LDX) use in patients with depressive disorder (DD) and bipolar disorder (BD), using only medical subject headings (MeSH). The following terms were used: “depressive disorder” [MeSH] OR “bipolar disorder” [MeSH] AND“ lisdexamfetamine dimesylate” [MeSH]. We selected articles published in Portuguese and English only, with no publication date restrictions. As an inclusion criterion, only articles that observed the profile of effects of LDX use in patients with mood disorders, with or without comorbid attention deficit and hyperactivity disorder, were included. Eight papers were selected, but only five were included in the narrative synthesis. We found few data on the use of LDX in mood disorders, but the results demonstrate a possible use to potentiate treatment and reduce cognitive impairment in patients with DD, as well as to improve metabolic syndrome parameters in patients with BD.

Lisdexamfetamine as an Add-On Treatment for Depression?

Most patients with unipolar depression experience residual symptoms after initial treatment, and those who experience only partial resolution have

Efficacy and tolerability of lisdexamfetamine as an antidepressant augmentation strategy: A meta-analysis of randomized controlled trials

BackgroundPsychostimulants have been used in the treatment of depression, with mixed results. This meta-analysis examines the efficacy and tolerability of the stimulant Lisdexamfetamine (LDX) as an add-on strategy in those with MDD who have failed to respond to an antidepressant. MethodRandomized control trials were identified and extracted from Pubmed; Web of Science; PsychINFO; and Cochrane Library. The efficacy of LDX was evaluated using Hedges’ g and Odds Ratio, whereas Risk Difference was used to assess the safety and tolerability of LDX. ResultsFour studies met inclusion criteria. LDX did not demonstrate superiority in efficacy relative to placebo as indicated by a Hedges’ g score of 0.126 (95% CI −0.040–0.291; p = 0.136) for mean change in Montgomery-Asberg Depression Rating Scale. Odds ratios of 1.206 (95% CI 0.745–1.954; p = 0.446) and 1.244 (95% CI 0.959–1.614; p = 0.1) were found for remission and response rates respectively. Risk differences of −0.1 (95% CI −0.155–(−0.045); p < 0.001) indicated a 10% increase chance of developing treatment-emergent adverse events (TEAE) in the LDX group. There was no significant difference in risk for developing serious or severe TEAE and discontinuing treatment due to TEAE. LimitationsThe number of included studies was small and only one metric was available for analysis of antidepressant efficacy of LDX. ConclusionsLDX when used as antidepressant augmentation produced a small effect in improving depressive symptoms that approached trend-level significance and demonstrated comparable tolerability to placebo. Further studies are needed to determine the optimal clinical subset of depressive symptoms responsive to LDX augmentation.

P.1.j.030 - Cognitive function in children and adolescents with ADHD receiving lisdexamfetamine dimesylate in a 2-year safety study

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common behavioural disorders of childhood; its prevalence in Spain is estimated at 5%-9%. Available treatments for this condition include methylphenidate, atomoxetine, and lisdexamfetamine, whose consumption increases each year.The prevalence of ADHD was estimated by calculating the defined daily dose per 1000 population per day of each drug and the total doses (therapeutic group N06BA) between 1992 and 2015 in each of the provinces of Castile-La Mancha (Spain). Trends, joinpoints, and annual percentages of change were analysed using joinpoint regression models.The minimum prevalence of ADHD in the population of Castile-La Mancha aged 5-19 was estimated at 13.22 cases per 1000 population per day; prevalence varied across provinces (P < .05). Overall consumption has increased from 1992 to 2015, with an annual percentage of change of 10.3% and several joinpoints (2000, 2009, and 2012). Methylphenidate represents 89.6% of total drug consumption, followed by lisdexamfetamine at 8%.Analysing drug consumption enables us to estimate the distribution of ADHD patients in Castile-La Mancha. Our data show an increase in the consumption of these drugs as well as differences in drug consumption between provinces, which reflect differences in ADHD management in clinical practice.El trastorno por déficit de atención e hiperactividad (TDAH) es uno de los trastornos conductuales más frecuentes de la infancia, se estima su prevalencia en España en un 5-9%. Existen varios fármacos para esta patología como el metilfenidato, la atomoxetina y la lisdexanfetamina cuyos consumos están creciendo anualmente.Se estima la prevalencia de TDAH a través del cálculo de las dosis diarias definidas por 1.000 habitantes y día de cada fármaco y el total (grupo terapéutico N06BA), durante los años 1992-2015, para cada una de las provincias de Castilla-La Mancha (España). Se observa la tendencia, sus puntos de cambio y los porcentajes anuales de cambio mediante modelos de regresión de joinpoint.Se estima una prevalencia mínima de TDAH de 13,22 casos por 1.000 habitantes y día para Castilla-La Mancha en la población de 5 a 19 años, existiendo una variabilidad provincial (p < 0,05). En su conjunto, el consumo se ha incrementado un porcentaje anual de cambio de 10,3% desde 1992 a 2015 con varios años o puntos de inflexión (2000, 2009 y 2012). El metilfenidato supone el 89,6% de los fármacos consumidos, seguido por la lisdexanfetamina con un 8%.El consumo de fármacos permite estimar la distribución de TDAH en Castilla-La Mancha. Se observa un crecimiento en el consumo de estos fármacos, y se observa una variabilidad provincial en su consumo, lo que supone diferencias en la práctica médica frente a esta enfermedad.

A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to antidepressant therapy

Background:This randomized, double-blind, placebo-controlled study evaluated dose-response relationships of lisdexamfetamine dimesylate when used as augmentation for major depressive disorder in individuals exhibiting inadequate responses to antidepressant monotherapy.Methods:Eligible adults (18–65 years) were assigned to antidepressant monotherapy (escitalopram or venlafaxine extended-release) plus lisdexamfetamine dimesylate-matching placebo during an eight-week single-blind lead-in phase. Participants meeting randomization criteria were randomized (1:1:1:1:1) to eight weeks of lisdexamfetamine dimesylate (10, 30, 50, or 70 mg) or placebo while maintaining antidepressant therapy. Dose-responses for changes from augmentation baseline to week 16/early termination for Montgomery-Åsberg Depression Rating Scale total score (primary efficacy endpoint) and vital signs (systolic and diastolic blood pressure and pulse) were assessed using multiple comparisons procedures with modeling.Results:For Montgomery-Åsberg Depression Rating Scale total score change, no significant dose-responses were observed for any candidate dose-response curve (all p>0.10). In the dose-response evaluable population, least squares mean (90% confidence interval) treatment differences versus placebo for Montgomery-Åsberg Depression Rating Scale total score change at week 16 were −1.4 (−3.9, 1.2), 0.1 (−2.5, 2.7), −0.7 (−3.4, 2.0), and −0.9 (−3.5, 1.6) with 10, 30, 50, and 70 mg lisdexamfetamine dimesylate, respectively. For all vital sign parameters, lisdexamfetamine dimesylate exhibited significant dose-responses for all candidate dose-response curves (all p<0.10), with increases observed as lisdexamfetamine dimesylate dose increased; a linear relationship provided the best fit. Mean±standard deviation changes from augmentation baseline for systolic and diastolic blood pressure and pulse at week 16/early termination were −0.7±9.90 and −0.3±7.24 mm Hg and 0.2±10.57 bpm with placebo and were 1.9±9.47 and 0.8±7.40 mm Hg and 3.6±9.74 bpm with lisdexamfetamine dimesylate (all doses combined). The safety and tolerability profile of lisdexamfetamine dimesylate was consistent with previous studies.Conclusions:Lisdexamfetamine dimesylate augmentation did not provide benefit over placebo in adults with inadequate responses to antidepressant monotherapy based on the assessed efficacy measures.

The Efficacy of Psychostimulants in Major Depressive Episodes: A Systematic Review and Meta-Analysis.

Psychostimulants are frequently prescribed off-label for adults with major depressive disorder or bipolar disorder. The frequent and increasing usage of stimulants in mood disorders warrants a careful appraisal of the efficacy of this class of agents. Herein, we aim to estimate the efficacy of psychostimulants in adults with unipolar or bipolar depression. The PubMed/Medline database was searched from inception to January 16, 2016 for randomized, placebo-controlled clinical trials investigating the antidepressant efficacy of psychostimulants in the treatment of adults with unipolar or bipolar depression. Psychostimulants were associated with statistically significant improvement in depressive symptoms in major depressive disorder (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.13-1.78; P = 0.003) and bipolar disorder (OR, 1.42; 95% CI, 1.13-1.78; P = 0.003). Efficacy outcomes differed across the psychostimulants evaluated as a function of response rates: ar/modafinil (OR, 1.47; 95% CI, 1.20-1.81; P = 0.0002); dextroamphetamine (OR, 7.11; 95% CI, 1.09-46.44; P = 0.04); lisdexamfetamine dimesylate (OR, 1.21; 95% CI, 0.94-1.56; P = ns); methylphenidate (OR, 1.49; 95% CI, 0.88-2.54; P = ns). Efficacy outcomes also differed between agents used as adjunctive therapy (OR, 1.39; 95% CI, 1.19-1.64) or monotherapy (OR, 2.25; 95% CI, 0.67-7.52). Psychostimulants are insufficiently studied as adjunctive or monotherapy in adults with mood disorders. Most published studies have significant methodological limitations (eg, heterogeneous samples, dependent measures, type/dose of agent). In addition to improvements in methodological factors, a testable hypothesis is that psychostimulants may be more appropriately tested in select domains of psychopathology (eg, cognitive emotional processing), rather than as "broad-spectrum" antidepressants.

Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder

The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Lisdexamfetamine administration. The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over placebo on the log-rank test (χ21, 40.37; P < .001) for time to relapse; the hazard ratio, based on a Cox proportional hazards model for lisdexamfetamine vs placebo, was 0.09 (95% CI, 0.04-0.23). The treatment-emergent adverse events observed were generally consistent with the known profile of lisdexamfetamine. Risk of binge-eating relapse over 6 months was lower in participants continuing lisdexamfetamine than in those randomized to placebo. The hazard for relapse was lower with lisdexamfetamine than placebo. clinicaltrials.gov Identifier: NCT02009163.

Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study.

The rationale of mesenchymal stem cells (MSCs) as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD) in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX). Wistar rats (n=65) received one oral daily dose of LDX (10 mg/kg) or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells) or lithium (47.5 mg/kg) as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004), and lithium reversed LDX-related hyperactive behavior (p<0.001). In contrast, the administration of MSCs did not change hyperlocomotion, indicating no effects of this treatment on LDX-treated rats (p=0.979). We did not find differences between groups in BDNF levels (p>0.05) in the hippocampus of rats. Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

43. Overview of Data Supporting the Efficacy of Lisdexamfetamine Dimesylate in the Treatment of Binge Eating Disorder

43. Overview of Data Supporting the Efficacy of Lisdexamfetamine Dimesylate in the Treatment of Binge Eating Disorder

Growth and sexual maturation in a 2-year, open-label clinical study of lisdexamfetamine dimesylate in children and adolescents with ADHD

IntroductionIndividuals with attention-deficit/hyperactivity disorder (ADHD) may require long-term medication.ObjectivesTo measure growth and sexual maturation of children and adolescents with ADHD receiving lisdexamfetamine dimesylate (LDX) in a 2-year trial (SPD489-404).AimsTo investigate the impact of long-term LDX treatment on growth and maturation.MethodsParticipants (6–17 years) received dose-optimized, open-label LDX (30–70 mg/day) for 104 weeks. Weight, height and BMI z-scores were derived using the Centers for Disease Control and Prevention norms [1]. Sexual maturation was assessed using the Tanner scale (participant-rated as closest to their stage of development based on standardized drawings).ResultsOf 314 enrolled participants, 191 (60.8%) completed the study. Mean z-scores at baseline and last on-treatment assessment (LOTA) were 0.53 (standard deviation, 0.963) and 0.02 (1.032) for weight, 0.61 (1.124) and 0.37 (1.131) for height, and 0.32 (0.935) and–0.27 (1.052) for BMI. In general, z-scores shifted lower over the first 36 weeks and then stabilized. At LOTA, most participants remained at their baseline Tanner stage or shifted higher, based on development of hair (males, 95.5%; females, 92.1%) or genitalia/breasts (males, 94.7%; females, 98.4%).ConclusionsConsistent with previous studies of stimulants used to treat ADHD [2], z-scores for weight, height and BMI decreased, mostly in the first year, then stabilized. No clinically concerning trends of LDX treatment on sexual maturation or the onset of puberty were observed.Disclosure of interestStudy funded by Shire Development LLC.Dr Isabel Hernández Otero (Alicia Koplowitz Foundation, Eli Lilly, Forest, Janssen-Cilag, Junta de Andalucia, Roche, Shire, Shire Pharmaceuticals Iberica S.L., and Sunovion).

A cost-effectiveness analysis of lisdexamfetamine dimesylate in the treatment of adults with attention-deficit/hyperactivity disorder in the UK

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder in children that may persist into adulthood. Lisdexamfetamine dimesylate (LDX) is approved in many countries for ADHD treatment in children, adolescents, and adults.ObjectivesEstimate the cost-effectiveness of LDX as a first- or second-line treatment for adults with ADHD from the United Kingdom (UK) National Health Service (NHS) perspective compared with methylphenidate extended release (MPH-ER) and atomoxetine (ATX).MethodsA 1-year decision-analytic model was developed. Health outcomes included response, non-response and inability to tolerate. Efficacy data were obtained from a mixed-treatment comparison (MTC). Response was a score of 1 or 2 on the Clinical Global Impression–Improvement scale. Tolerability was assessed by discontinuation rates due to adverse events. Utilities were identified via a systematic literature review. Health care resource use estimates were obtained via a survey of clinicians. Daily drug costs were estimated from mean doses reported in the trials used in the MTC. One-way and probabilistic sensitivity analyses (PSAs) were performed.ResultsLDX dominated MPH-ER and ATX; reducing mean per-patient annual cost by £5 and £200, and increasing mean quality-adjusted life years (QALYs) by 0.005 and 0.009, respectively. In the PSA, the probability of cost-effectiveness for LDX vs. MPH-ER and ATX at a threshold of £20,000 per QALY was 61% and 80%, respectively.ConclusionsFrom the perspective of the UK NHS, LDX is likely to provide a cost-effective treatment for adults with ADHD. This conclusion may be drawn with more certainty in comparison with ATX than with MPH-ER.

Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder.

Lisdexamfetamine dimesylate (LDX) is the first prodrug stimulant used for the treatment of attention-deficit/hyperactivity disorder (ADHD) dosed once daily. Due to its long-acting properties, LDX remains pharmacologically inactive until an enzymatic process predominantly associated with red blood cells converts it to the active ingredient, d-amphetamine and the amino acid lysine. The efficacy of LDX over placebo has been demonstrated in several studies in adults with moderate to severe ADHD with significant improvements noted in ADHD rating scales, Clinical Global Improvement scores, and assessments of executive function, for all doses of LDX (30-70 mg daily). Lisdexamfetamine dimesylate has demonstrated efficacy at 14 hours post dose in adults and may be used as a long-acting stimulant for managing ADHD symptoms, which may extend late into the day. Lisdexamfetamine dimesylate has demonstrated a safety profile consistent with long-acting stimulants use. Relevant English language articles were identified through computerized searches of MEDLINE (PubMed and EMBASE) from 1995 to 2016 using the following search terms: lisdexamfetamine dimesylate, attention-deficit hyperactivity disorder, NRP104, and Vyvanse.

Shire announces new update to BED medication labeling

Vyvanse (lisdexamfetamine dimesylate) labeling has been updated to include information regarding the approval of a supplemental New Drug Application by the Food and Drug Administration (FDA). The labeling will now include maintenance of efficacy data from the first‐ever longer‐term pharmacologic study (38 weeks) in adults with moderate‐to‐severe binge eating disorder (BED), Shire officials announced. The data were presented at a few medical conferences including the Eating Disorders Association of Canada in September, and during the American College of Neuropsychopharmacology Annual Meeting a year ago. The updated labeling is based on a long‐term study showing that adults with moderate‐to‐severe BED who responded to Vyvanse were much more likely to stay in remission than if they stayed on placebo, Susan L. McElroy, M.D., professor of psychiatry and behavioral neuroscience at the University of Cincinnati College of Medicine, told CPU.