Lisdexamfetamine 40mg capsules

ImportanceThe use of stimulant medications has expanded substantially beyond the traditional treatment of attention-deficit/hyperactivity disorder (ADHD) to encompass a variety of other clinical conditions. Understanding the safety of these medications is important as their use increases across diverse patient populations.ObjectiveTo assess the safety of stimulant medications as reported in randomized clinical trials (RCTs) investigating methylphenidate, lisdexamfetamine, and other amphetamines.Data sourcesA comprehensive literature search was conducted from July 1, 2024, through February 28, 2025, using CINAHL, Embase, PubMed or MEDLINE, ScienceDirect, and Web of Science for studies published since 2000. Keywords included safety, adverse event, side effect, amphetamine, dextroamphetamine, stimulant, lisdexamfetamine, and methylphenidate.Study selectionRCTs published between January 1, 2000, and December 13, 2024, were included. These trials investigated the safety of stimulants in various clinical conditions, including ADHD, depression, binge eating disorder, schizophrenia, Alzheimer disease, and stimulant use disorders as well as in healthy individuals. Trials not focused on safety or adverse events (AEs) of stimulants, nonoriginal research, nonhuman research, trials with concomitant prescriptions other than stimulants, and trials without a placebo group were excluded.Data extraction and synthesisData extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Independent reviewers extracted study data, and a random-effects model was used to pool results. Heterogeneity was assessed using the I2 statistic.Main outcomes and measuresThe primary outcome was the risk ratio (RR) of developing any AE in participants taking stimulants vs placebo.ResultsA total of 93 RCTs were included after exclusions. The methodological quality assessment of the included trials showed overall low or unclear risk of bias. Trials with a duration of up to 52 weeks showed that stimulant medications were associated with an increased risk of overall AEs compared with placebo (RR, 1.34; 90% CI, 1.27-1.41), with high heterogeneity (I2 = 67%). Statistical significance of this finding was maintained when subgroups (ie, methylphenidate, lisdexamfetamine, and other amphetamines) were separately analyzed.Conclusions and relevanceThis meta-analysis found an increased risk of overall AEs associated with stimulants compared with placebo. Future research could provide more standardized and consistent assessments of this outcome and may improve understanding about misuse risk.

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Abstract Background: Lisdexamfetamine is a long-acting amphetamine-based prodrug widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Its gradual conversion into dextroamphetamine provides a predictable pharmacokinetic profile, but its sympathomimetic activity may affect cardiovascular parameters, particularly heart rate, blood pressure, and electrocardiographic findings. This systematic review aimed to synthesize the available evidence on the cardiovascular effects and safety of lisdexamfetamine in individuals with ADHD and healthy volunteers. Methods: This systematic review was conducted according to PRISMA 2020 recommendations and prospectively registered in PROSPERO. Searches were performed in PubMed/MEDLINE, Embase, Cochrane Library, Google Scholar, and SciELO for studies published between January 2000 and March 2026. Eligible studies included clinical trials, open-label extension studies, observational studies, pharmacokinetic/pharmacodynamic studies, case reports, and systematic reviews reporting cardiovascular outcomes or safety data related to lisdexamfetamine. Study selection was performed in Rayyan, and risk of bias was assessed using tools appropriate to each study design, including RoB 2, the Newcastle–Ottawa Scale, and AMSTAR 2. Results: A total of 727 records were identified, of which 99 duplicates were removed. After screening 628 titles and abstracts, 70 full-text reports were assessed for eligibility, and 20 studies were included in the final synthesis. Across pediatric, adult, and healthy volunteer populations, lisdexamfetamine was consistently associated with small mean increases in heart rate, generally ranging from 4 to 7 beats per minute, and modest increases in systolic and diastolic blood pressure, usually between 1 and 4 mmHg. Available studies did not show consistent evidence of clinically meaningful QTc prolongation or a significant increase in serious cardiovascular adverse events. However, most clinical studies excluded individuals with relevant cardiovascular disease or uncontrolled hypertension, limiting the generalizability of these findings to higher-risk populations. Conclusions: Lisdexamfetamine appears to have an overall favorable cardiovascular safety profile in selected and clinically monitored populations. Its main cardiovascular effects are modest increases in heart rate and blood pressure, consistent with its sympathomimetic mechanism. Nevertheless, individualized cardiovascular assessment and regular monitoring remain necessary, especially during long-term treatment and in patients with pre-existing cardiovascular risk factors.

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Abstract Aims This study tested the efficacy and safety of a 12‐week course of lisdexamfetamine in reducing methamphetamine use, an outcome which is associated with improvements in health and wellbeing, in people dependent on methamphetamine. Design, setting and participants This study was a randomised double‐blind placebo‐controlled trial conducted in six specialist outpatient clinics in Adelaide, Melbourne, Newcastle and Sydney, Australia (2018–2021). Participants were164 adults with methamphetamine dependence, reporting at least 14 use days out of the previous 28 days (62% male, 38% female, < 1% other; mean age 39 years). Interventions Participants were randomly allocated 1:1 to a 15‐week regimen of lisdexamfetamine (1‐week induction to 250 mg, 12‐week maintenance regimen, 2‐week reduction; n = 80) or matched placebo (n = 84), followed‐up to Week 19. Measurements The primary efficacy measure was past 28‐day methamphetamine use at Week 13. Safety was assessed by adverse event rates. Secondary measures included methamphetamine use during the 12‐week treatment period and treatment satisfaction. Findings Nine randomized participants did not start treatment (five were allocated to lisdexamfetamine and four allocated to placebo) and were excluded from the analyses. Fifty‐seven per cent of participants were retained on study medication to primary end‐point. There was only weak evidence of a lisdexamfetamine benefit at 13 weeks [adjusted difference in days of methamphetamine use = 2.2, 95% confidence interval (CI) = –0.5 to 5.0; P = 0.49]. However, throughout the whole 12‐week treatment maintenance phase, the lisdexamfetamine group had fewer days of methamphetamine use in total (difference = 8.8, 95% CI = 2.7–15.0; P = 0.005). The lisdexamfetamine group reported greater self‐reported treatment effectiveness [odds ratio (OR) = 2.89, 95% CI = 1.67–5.02; P < 0.001] and treatment satisfaction (OR = 3.80, 95% CI = 1.93–7.47; P < 0.001). Adverse events with lisdexamfetamine included nausea. Serious adverse events occurred in four (5%) of participants who received lisdexamfetamine. Conclusions Lisdexamfetamine appears to reduce methamphetamine use over a 12‐week treatment period, although there is only weak evidence that reduced use is maintained during the last 4 weeks.

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Background: Controlled research examining maintenance treatments for responders to acute interventions for binge-eating disorder (BED) is limited. This study tested efficacy of lisdexamfetamine (LDX) maintenance treatment amongst acute responders. Methods: Prospective randomized double-blind placebo-controlled single-site trial, conducted March 2019 to September 2023, tested LDX as maintenance treatment for responders to acute treatments with LDX-alone or with cognitive-behavioral therapy (CBT+LDX) for BED with obesity. Sixty-one (83.6% women, mean age 44.3, mean BMI 36.1 kg/m2) acute responders were randomized to LDX (N=32) or placebo (N=29) for 12 weeks; 95.1% completed posttreatment assessments. Mixed-models and generalized-estimating equations comparing maintenance LDX versus placebo included main/interactive effects of acute (LDX or CBT+LDX) treatments to examine their predictive/moderating effects. Results: Relapse rates (to diagnosis-level binge-eating frequency) following maintenance treatments were 10.0% (N=3/30) for LDX and 17.9% (N=5/28) for placebo; intention-to-treat binge-eating remission rates were 59.4% (N=19/32) and 65.5% (N=19/29), respectively. Maintenance LDX and placebo did not differ significantly in binge-eating but differed in weight-loss and eating-disorder psychopathology. Maintenance LDX was associated with significant weight-loss (−2.3%) whereas placebo had significant weight-gain (+2.2%); LDX and placebo differed significantly in weight-change throughout treatment and posttreatment. Eating-disorder psychopathology remained unchanged with LDX but increased significantly with placebo. Acute treatments did not significantly predict/moderate maintenance-treatment outcomes. Conclusions: Adults with BED/obesity who respond to acute lisdexamfetamine treatment (regardless of additionally receiving CBT) had good maintenance during subsequent 12-weeks. Maintenance lisdexamfetamine, relative to placebo, did not provide further benefit for binge-eating but was associated with significantly better eating-disorder psychopathology outcomes and greater weight-loss. Clinicaltrials.gov registration: NCT03926052 (Cognitive-Behavioral and Pharmacologic (LDX) Treatment of Binge-Eating Disorder and Obesity: Maintenance Treatment)

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