Update on optimal use of lisdexamfetamine in the treatment of ADHD
Open accessAbstract
Lisdexamfetamine (LDX) has been a recent addition to the treatment armamentarium for Attention Deficit Hyperactivity Disorder (ADHD). It is unique among stimulants as it is a prodrug, and has been found to be safe and well-tolerated medication in children older than 6 years, adolescents and adults. It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms. LDX has proven to be effective in the treatment of ADHD in placebo controlled trials, and improved performance in simulated academic and work environments have been noticed. Both stimulant-naïve and stimulant-exposed patients with ADHD appear to benefit from LDX. It has also shown some promise in improving emotional expression and executive function of patients with ADHD. Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations. Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant. Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion. There is a need for future studies comparing other long acting stimulants with LDX in ADHD; in fact clinical trials comparing LDX with OROS (osmotic controlled-release oral delivery system) methylphenidate are currently underway. Furthermore, the utility of this medication in other psychiatric disorders and beyond ADHD is being investigated.
AI snapshot
Written from the paper’s full text.
TL;DR
This narrative review summarizes the pharmacology, safety, tolerability, and efficacy of lisdexamfetamine (LDX), the only stimulant prodrug approved for ADHD, in children, adolescents, and adults. It concludes LDX is safe, well tolerated, and efficacious, with a smooth onset, up to 13-hour duration, and possibly lower abuse potential, while noting the absence of head-to-head trials against other long-acting stimulants.
Key findings
- LDX is a prodrug of dextroamphetamine plus lysine, hydrolyzed in red blood cells and not metabolized by hepatic cytochrome P450, giving low drug–drug interaction potential; dosing starts at 30 mg/day and can be titrated to a maximum of 70 mg/day in weekly 10–20 mg increments.
- In a Phase III forced-dose trial of 290 children (6–12 years), ADHD-RS-IV reductions were 4–5-fold greater than placebo (P < 0.001), largest in the 70 mg group; 9% withdrew due to adverse effects, with a mild heart rate increase of 4–5 beats per minute.
- Common adverse events were transient decreased appetite, weight loss, insomnia, headache, irritability, and upper abdominal pain; no statistically significant changes in vital signs, laboratory work, or electrocardiograms were noted.
- Abuse-liability studies in subjects with stimulant-abuse histories found intravenous LDX 25–50 mg and oral 50–100 mg were similar to placebo on liking scales, whereas 150 mg was equivalent to 40 mg immediate-release dextroamphetamine; a 15-month follow-up of 282 children showed slowed growth on weight, height, and BMI versus CDC norms.
Methods
- Narrative review ("overview of the recent literature") of LDX covering pharmacology, safety, tolerability, and efficacy profiles; no systematic search strategy or inclusion criteria are described.
- Synthesizes pharmacokinetic studies in healthy volunteers and children, randomized placebo-controlled and crossover trials, open-label dose-optimization and long-term extension studies, and post hoc analyses across child, adolescent, and adult ADHD populations.
- Cited trials include analog classroom, laboratory school, simulated workplace, driving-simulator, and abuse-liability designs; sample sizes range from 8 to 420 participants.
Limitations
- Stated by the paper: available studies are limited by being predominantly pharmaceutical industry trials, having shorter randomized controlled trial durations, using open-label designs for longer studies, and lacking head-to-head trials with comparable agents (eg, LDX versus extended-release methylphenidate or MAS XR).
- Stated by the paper: most studies exclude subjects with psychiatric and general medical comorbidities, so prescribing precautions are advised for patients with tic disorder, hypertension, or significant family history of cardiovascular disease; safety and efficacy in ages 3–5 years has not been established.
- Evident from the text: as a narrative review without a described systematic search or quality appraisal, study selection and synthesis may be subject to selection bias; several cited efficacy findings rest on post hoc analyses and small open-label studies (eg, 8 adolescents, 13–14 children per group).
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
8 of 60 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
- Premisecitation
In Turgay et al 7-week open-label study of 319 children aged 6-12 years with ADHD, lisdexamfetamine produced significant improvements in ADHD-RS-IV, BRIEF, and EESC scores.
“In a 7-week, open-label study of 319 children (6–12 years) with ADHD, Turgay et al35 found significant improvements in ADHD-RS-IV, BRIEF, and EESC scores.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [35] Turgay A Ginsberg L Sarkis E Executive function deficits in children with attention-deficit/hyperactivity disorder and improvement with lisdexamfetamine dimesylate in an open-label study J Child Adolesc Psychopharmacol 2010 20 6 503 511 21186969 PMC3005278 source
The Methods describe a 7-week open-label lisdexamfetamine study in children aged 6–12 with ADHD. The Results report significant improvements in ADHD-RS-IV, BRIEF, and EESC scores, but our copy does not establish the claimed total of 319 children: it reports 317 in the safety population and 308 with baseline and endpoint BRIEF measurements. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Premisecitation
In that study, drug accountability records showed that 90% of the unreturned medication was presumably taken as prescribed.
“Drug accountability records showed that 90% of the unreturned medication was “presumably having taking the pills as prescribed”.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [41] Donovan SJ Levin FR The “younger-sibling-at-risk design”: a pilot study of adolescents with ADHD and an older sibling with substance use disorder Am J Drug Alcohol Abuse 2011 37 40 235 239 21517711 PMC3154771 source
- Premisecitation
In a simulated workplace environment, Wigal et al noted a consistent improvement in PERMP scores in ADHD subjects treated with lisdexamfetamine compared with placebo.
“In a simulated workplace environment, Wigal et al38 noted a consistent improvement in Permanent Product Measure of Performance scores in ADHD subjects treated with lisdexamfetamine in comparison with placebo.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [38] Wigal T Brams M Gasior M Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design Behav Brain Funct 2012 6 1 34 20576091 PMC2908054 source
- Premisecitation
In Jain et al post hoc analysis of two large studies in children switched from methylphenidate to lisdexamfetamine, the subgroup with prior methylphenidate treatment showed significant improvement in ADHD-RS-IV scores comparable with overall results from the two open-label trials.
“The subgroup with prior methylphenidate treatment showed significant improvement in ADHD-RS-IV scores, which were comparable with overall results from the two open-label trials.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [32] Jain R Babcock T Burtea T Efficacy and safety of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder and recent methylphenidate use Adv Ther 5 17 2013 [Epub ahead of print.] PMC3680667 23681505 source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
- Premisecitation
Lisdexamfetamine is a prodrug that requires enzymatic breakdown before becoming the active dextroamphetamine.
“It is unique among stimulants as it is a prodrug”
- Also stated in: § Introduction · plain
“it differs from other available extended-release stimulant formulations because of its mechanism of action as a prodrug which requires enzymatic breakdown before becoming the active, dextroamphetamine.7”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] Madaan V Lisdexamfetamine dimesylate for childhood ADHD Drugs Today (Barc) 2008 44 5 319 324 18548134 source
- Also stated in: § Introduction · plain
- Premisecitation
Absorption of lisdexamfetamine was not significantly affected whether it was administered with or without food or as a solution.
“Absorption was not significantly affected whether lisdexamfetamine was administered with or without food or as a solution.9”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] Goodman DW Lisdexamfetamine dimesylate: the first prodrug stimulant Psychiatry (Edgmont) 2007 4 8 39 45 20532026 PMC2880945
- Premisenone given
Most available studies of lisdexamfetamine exclude subjects with psychiatric and general medical comorbidities.
“However, it should be noted that most of the available studies exclude subjects with psychiatric and general medical comorbidities.”
Quote in the paperSubstantial claim - Interpretationreasoning
Because lisdexamfetamine is a single enantiomer, it may have lesser propensity to cause adverse reactions compared with mixed-amphetamine extended-release salts (MAS XR).
“Because it is a single enantiomer, it may have lesser propensity to cause adverse reactions compared with mixed-amphetamine extended-release salts (MAS XR, a 3:1 dextro:levo mixture).”
Quote in the paperNot a substantial claim - Premisenone given
The common theme from available studies is transient treatment emergent adverse events including decreased appetite, decreased weight, irritability, insomnia, headache, upper abdominal pain, and initial insomnia, which improve over time.
“In terms of safety and tolerability, the common theme from the available studies is the presence of transient treatment emergent adverse events, including decreased appetite, decreased weight, irritability, insomnia, headache, upper abdominal pain, and initial insomnia, which improve over time.”
Quote in the paperSubstantial claim - Premisenone given
No statistically significant changes in vital signs, laboratory work, and electrocardiographic readings have been noted with lisdexamfetamine.
“No statistically significant changes in vital signs, laboratory work, and electrocardiographic readings have been noted.”
Quote in the paperSubstantial claim - Premisecitation
In that trial, insomnia, decreased appetite, and anorexia were the most common adverse effects noticed with lisdexamfetamine.
“Insomnia, decreased appetite, and anorexia were the most common adverse effects noticed with lisdexamfetamine.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Biederman J Boellner S W Childress A Lopez FA Krishnan S Zhang Y Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study Biol Psychiatry 2007 62 9 970 976 17631866 source
- Premisecitation
In healthy adult volunteers, a steady-state concentration of dextroamphetamine following administration of lisdexamfetamine 70 mg was achieved by day 5.
“In healthy adult volunteers, a steady-state concentration of dextroamphetamine following administration of lisdexamfetamine 70 mg was achieved by day 5.12”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Krishnan SM Stark JG Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers Curr Med Res Opin 2008 24 1 33 40 18021493 source
- Premisecitation
In healthy adult volunteers, lisdexamfetamine 50 mg administered via oral capsules and InteliSite delivery capsules designed to release the drug selectively in selected small intestinal regions produced consistent mean peak plasma concentration and area under the curve for dextroamphetamine.
“Consistent levels of mean peak plasma concentration (Cmax) and area under the curve for dextroamphetamine were recorded when healthy adult volunteers were administered lisdexamfetamine 50 mg using oral capsules and InteliSite™ delivery capsules (Casper Associates, Raleigh, NC, USA) designed to release the drug selectively in selected small intestinal regions.13”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Ermer JC Haffey MB Doll WJ Pharmacokinetics of lisdexamfetamine dimesylate after targeted gastrointestinal release or oral administration in healthy adults Drug Metab Dispos 2012 40 2 290 297 22039171 source
- Premisecitation
In children with ADHD, lisdexamfetamine doses of 30 mg, 50 mg, and 70 mg produced a dose-proportional increase in the area under the curve and Cmax of dextroamphetamine with low interpatient variability.
“A dose-proportional increase in the area under the curve and Cmax of dextroamphetamine with low interpatient variability was demonstrated in children with ADHD using doses of 30 mg, 50 mg, and 70 mg.15”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] Boellner S W Stark JG Krishnan S Zhang Y Pharmacokinetics of lisdexamfetamine dimesylate and its active metabolite, d-amphetamine, with increasing oral doses of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: a single-dose, randomized, open-label, crossover study Clin Ther 2010 32 2 252 264 20206783 source
- Interpretationreasoning
Overall, lisdexamfetamine has been demonstrated to be well tolerated in child-adolescent and adult populations.
“Overall, lisdexamfetamine has been demonstrated to be well tolerated in child-adolescent and adult populations.”
Quote in the paperSubstantial claim - Premisecitation
In that trial, 9% of the subjects withdrew due to adverse effects.
“However, 9% of the subjects withdrew due to adverse effects.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Biederman J Krishnan S Zhang Y McGough JJ Findling RL Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study Clin Ther 2007 29 3 450 463 17577466 source
- Premisecitation
In Weisler et al 12-month follow-up of 349 patients (completed by 191 patients), the statistically significant improvement in ADHD-RS-IV score found in the previous study was maintained throughout the follow-up study.
“Weisler et al28 recruited 349 patients from the study by Adler et al27 for a 12-month, follow-up study, which was completed by 191 patients. The statistically significant improvement in ADHD-RS-IV score found in the previous study was maintained throughout the follow-up study.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Weisler R Young J Mattingly G Long-term safety and effectiveness of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder CNS Spectr 2009 14 10 573 585 20095369 source
- Premisecitation
In Brams et al randomized withdrawal study of 116 adults with ADHD stable on lisdexamfetamine, most patients switched to the placebo group relapsed within 2 weeks.
“Brams et al30 used a novel design of randomized withdrawal, in which 116 adult patients with ADHD and stable on lisdexamfetamine were randomized to placebo or lisdexamfetamine. Their results showed that most of the patients switched to the placebo group relapsed within 2 weeks.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [30] Brams M Weisler R Findling RL Maintenance of efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: randomized withdrawal design J Clin Psychiatry 2012 73 7 977 983 22780921 source
- Premisecitation
A post hoc analysis by Mattingly et al showed that lisdexamfetamine was effective for all subtypes of ADHD.
“A post hoc analysis of this study by Mattingly et al29 showed that lisdexamfetamine was effective for all the subtypes of ADHD.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Mattingly G Weisler R Dirks B Attention deficit hyperactivity disorder subtypes and symptom response in adults treated with lisdexamfetamine dimesylate Innov Clin Neurosci 2012 9 5–6 22 30 22808446 PMC3398683
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
In that study, heart rate recovery was elevated by 4 beats per minute.
“Interestingly, heart rate recovery was elevated by 4 beats per minute in this study.20”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Hammerness P Zusman R Systrom D A cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder World J Biol Psychiatry 2013 14 4 299 306 22559155 source
- Premisecitation
In that trial, consistent improvements were noted on the Conner's Parent Rating Scale-Revised Short Form at 10 am, 2 pm, and 6 pm.
“Consistent improvements were also noted on the Conner’s Parent Rating Scale-Revised Short Form at 10 am, 2 pm, and 6 pm.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Biederman J Krishnan S Zhang Y McGough JJ Findling RL Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study Clin Ther 2007 29 3 450 463 17577466 source
- Premisecitation
In a 15-month follow-up of 282 children treated with lisdexamfetamine, Faraone et al showed slowing of growth in weight, height, and body mass index compared with Centers for Disease Control norms.
“In a 15-month follow-up of 282 children treated with lisdexamfetamine, Faraone et al25 used weight, height, and body mass index to show that there was slowing of growth on all the above parameters when compared with Centers for Disease Control norms.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Faraone S V Spencer TJ Kollins SH Glatt SJ Effects of lisdexamfetamine dimesylate treatment for ADHD on growth J Am Acad Child Adolesc Psychiatry 2010 49 1 24 32 20215923 source
- Premisecitation
Brown et al small open-label study showed a statistically significant improvement in executive functioning in ADHD subjects treated with lisdexamfetamine using the Brown Attention-Deficit Disorder Scale.
“Other research that examined the efficacy of lisdexamfetamine in an academic or work environment includes a small open-label study Brown et al37 that showed a statistically significant improvement in executive functioning in ADHD subjects treated with lisdexamfetamine using the Brown Attention-Deficit Disorder Scale.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] Brown TE Brams M Gao J Gasior M Childress A Open-label administration of lisdexamfetamine dimesylate improves executive function impairments and symptoms of attention-deficit/hyperactivity disorder in adults Postgrad Med 2012 122 5 7 17 20861583 source
- Study design and conductcitation
The original study was limited by exclusion of patients with psychiatric comorbidity.
“However, it should be noted that the original study was limited by exclusion of patients with psychiatric comorbidity.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [36] Katic A Ginsberg L Jain R Clinically relevant changes in emotional expression in children with ADHD treated with lisdexamfetamine dimesylate J Atten Disord 2012 16 5 384 397 21173426 source
- Premisecitation
Despite these two serious adverse events, high levels of satisfaction with medication were reported by parents on the Medication Satisfaction Questionnaire during the trial.
“Despite these two serious adverse events, high levels of satisfaction with medication were reported by parents on the Medication Satisfaction Questionnaire during the trial.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] Findling RL Ginsberg LD Jain R Gao J Effectiveness, safety, and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: an open-label, dose-optimization study J Am Acad Child Adolesc Psychiatry 2009 19 6 649 662 20035583 source
- Premisecitation
In Wigal et al open-label dose-optimization study of 26 children with ADHD, lisdexamfetamine 30-70 mg produced improvements in rate, accuracy, and comprehension measures on the Gray Oral Reading Test-4 after 4-5 weeks of treatment.
“Wigal et al34 demonstrated improvements in rate, accuracy, and comprehension measures on the Gray Oral Reading Test-4 performed at baseline and after 4–5 weeks of treatment in a “modified laboratory school” setting.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] Wigal SB Maltas S Crinella F Reading performance as a function of treatment with lisdexamfetamine dimesylate in elementary school children diagnosed with ADHD J Atten Disord 2012 16 1 23 33 20978273 source
- Premisecitation
Study subjects on lisdexamfetamine have been reported to have low scores on drug likability scales, even with intravenous use.
“Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [42] Jasinski DR Krishnan S Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers J Psychopharmacol 2009 23 4 410 418 18635707 source
- cites [43] Weber J Siddiqui MA Lisdexamfetamine dimesylate: in attention-deficit hyperactivity disorder in adults CNS Drugs 2009 23 5 419 425 19453202 source
- Interpretationnone given
Both stimulant-naïve and stimulant-exposed patients with ADHD appear to benefit from lisdexamfetamine.
“Both stimulant-naïve and stimulant-exposed patients with ADHD appear to benefit from LDX.”
Quote in the paperNot a substantial claim - Interpretationcitation
Lisdexamfetamine has proven to be effective in the treatment of ADHD in placebo-controlled trials.
“LDX has proven to be effective in the treatment of ADHD in placebo controlled trials”
Quote in the paperSubstantial claim - Interpretationcitation
Improved performance in simulated academic and work environments has been noticed with lisdexamfetamine.
“and improved performance in simulated academic and work environments have been noticed.”
Quote in the paperSubstantial claim - Premisecitation
In Weber et al randomized six-step crossover Phase I study in individuals with a history of stimulant abuse, compared with placebo, dextroamphetamine and diethylpropion produced significant differences on the Drug Rating Questionnaire-Subject Liking Scale.
“A randomized, six-step, crossover Phase I study43 in individuals with a history of stimulant abuse using placebo, lisdexamfetamine 50 mg, 100 mg, and 150 mg, immediate-release dextroamphetamine 40 mg, diethylpropion 200 mg, and placebo showed that, compared with placebo, dextroamphetamine and diethylpropion produced significant differences on the Drug Rating Questionnaire-Subject Liking Scale.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [43] Weber J Siddiqui MA Lisdexamfetamine dimesylate: in attention-deficit hyperactivity disorder in adults CNS Drugs 2009 23 5 419 425 19453202 source
- Interpretationcitation
Lisdexamfetamine has shown some promise in improving emotional expression and executive function of patients with ADHD.
“It has also shown some promise in improving emotional expression and executive function of patients with ADHD.”
Quote in the paperSubstantial claim - Premisecitation
In a recent double-blind, placebo-controlled study of 26 patients, Young showed an improvement in both fatigue and executive function in patients with chronic fatigue syndrome.
“In a recent double-blind, placebo-controlled study of 26 patients, Young46 showed an improvement in both fatigue and executive function in patients with chronic fatigue syndrome.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [46] Young JL Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study Psychiatry Res 2013 207 1–2 127 133 23062791 source
- Interpretationcitation
Lisdexamfetamine may have somewhat less potential for abuse and diversion.
“Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion.”
Quote in the paperSubstantial claim
- May combine two claims. 38
- Classified as probably not a substantial claim. 5
- The quote only partly states this claim. 1
May combine two claims.
PremisecitationLisdexamfetamine enters the portal circulation unchanged via the peptide protein transporter system, and the covalent linkage between lysine and dextroamphetamine is broken down by hydrolysis in the red blood cell.
“Lisdexamfetamine enters the portal circulation unchanged via the peptide protein transporter system, and the covalent linkage between lysine and dextroamphetamine is broken down by hydrolysis in the red blood cell.10”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [10] Pennick M Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine Neuropsychiatr Dis Treat 2010 6 317 327 20628632 PMC2898170 source
May combine two claims.
PremisecitationLisdexamfetamine contains the active ingredient dextroamphetamine and the amino acid lysine.
“Lisdexamfetamine contains the active ingredient dextroamphetamine and the amino acid lysine.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [10] Pennick M Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine Neuropsychiatr Dis Treat 2010 6 317 327 20628632 PMC2898170 source
May combine two claims.
PremisecitationIn Wigal et al 13-hour laboratory school study of 117 children aged 6-12 years with ADHD, lisdexamfetamine produced statistically significant improvements on SKAMP deportment, SKAMP attention, and PERMP scales (P < 0.001) compared with placebo.
“Statistically significant improvements were noted on the SKAMP deportment rating, SKAMP attention, and Permanent Product Measure of Performance scales (P < 0.001).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [33] Wigal SB Kollins SH Childress AC Squires L A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder Child Adolesc Psychiatry Ment Health 2009 3 1 17 19508731 PMC2704174 source
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationIn Donovan and Levin open-label study of eight adolescents with ADHD whose older siblings had substance misuse problems, subjects showed improvement in ADHD symptoms and on the modified Pretcher and Nash scale measuring perceived benefit of substance abuse.
“In an open-label lisdexamfetamine study with an innovative design, Donovan and Levin41 treated eight adolescents with ADHD whose older siblings had substance misuse problems. In addition to improvement in ADHD symptoms, the subjects also showed an improvement on the modified Pretcher and Nash scale which measures perceived benefit of substance abuse.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [41] Donovan SJ Levin FR The “younger-sibling-at-risk design”: a pilot study of adolescents with ADHD and an older sibling with substance use disorder Am J Drug Alcohol Abuse 2011 37 40 235 239 21517711 PMC3154771 source
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
May combine two claims.
Study design and conductnone givenThe available studies on lisdexamfetamine are limited by predominantly pharmaceutical industry trials, shorter duration of randomized controlled trials, open-label designs for longer duration studies, and the unavailability of head-to-head trials with comparable agents.
“the available studies on lisdexamfetamine are limited by several factors, including predominantly pharmaceutical industry trials, shorter duration of randomized controlled trials, open-label designs for longer duration studies, and the unavailability of head-to-head trials with comparable agents”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationIn Biederman et al Phase II trial of 52 children aged 6-12 years with ADHD, both MAS XR and lisdexamfetamine produced statistically significant improvement (P < 0.001) measured by SKAMP, PERMP, and CGI.
“There was a statistically significant improvement (P < 0.001) in both the MAS XR and lisdexamfetamine groups. This was measured using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP), Permanent Product Measure of Performance (PERMP), and the Clinical Global Impression (CGI) rating scales.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Biederman J Boellner S W Childress A Lopez FA Krishnan S Zhang Y Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study Biol Psychiatry 2007 62 9 970 976 17631866 source
May combine two claims.
PremisecitationTime to reach maximal concentration was delayed by one hour when 70 mg of lisdexamfetamine was administered with food compared with the fasting state in healthy adult volunteers, but there was no change in Cmax levels.
“Time to reach maximal concentration was delayed by one hour when 70 mg of lisdexamfetamine was administered with food compared with the fasting state in healthy adult volunteers, but there was no change in Cmax levels.14”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] Krishnan S Zhang Y Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study J Clin Pharmacol 2008 48 3 293 302 18285619 source
May combine two claims.
PremisecitationLisdexamfetamine is not metabolized by the hepatic cytochrome P450 system, so it has a low potential for drug-drug interactions.
“Krishnan and Moncrief demonstrated that lisdexamfetamine is not metabolized by the hepatic cytochrome P450 system, so lisdexamfetamine has a low potential for drug–drug interactions.11”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Krishnan S Moncrief S An evaluation of the cytochrome p450 inhibition potential of lisdexamfetamine in human liver microsomes Drug Metab Dispos 2007 35 1 180 184 17035599 source
May combine two claims.
PremisecitationOral and intranasal administration of lisdexamfetamine in healthy adult volunteers showed similar Cmax, area under the curve, and time to reach maximal concentration, with low intersubject variability and similar tolerability rates for both routes.
“Oral and intranasal administration of lisdexamfetamine in healthy adult volunteers showed a similar Cmax, area under the curve, and time to reach maximal concentration, with low intersubject variability and similar tolerability rates for both routes of administration.16”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Ermer JC Dennis K Haffey MB Intranasal versus oral administration of lisdexamfetamine dimesylate: a randomized, open-label, two-period, crossover, single-dose, single-centre pharmacokinetic study in healthy adult men Clin Drug Investig 2011 31 6 357 370 21539403 source
May combine two claims.
PremisecitationIn that trial, small changes in diastolic blood pressure and pulse rate, along with changes in the QTc interval, were noted but were not clinically or statistically significant.
“Small changes in diastolic blood pressure and pulse rate, along with changes in the QTc interval, were noted but were not clinically or statistically significant.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Biederman J Boellner S W Childress A Lopez FA Krishnan S Zhang Y Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study Biol Psychiatry 2007 62 9 970 976 17631866 source
May combine two claims.
PremisecitationLisdexamfetamine is the only stimulant prodrug available, and its unique formulation may help lower the potential for abuse, toxicity in overdose, and likelihood of drug tampering.
“Lisdexamfetamine is currently the only stimulant prodrug available, with a unique formulation that may help to lower the potential for abuse, toxicity in cases of overdose, and the likelihood of drug tampering.9”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] Goodman DW Lisdexamfetamine dimesylate: the first prodrug stimulant Psychiatry (Edgmont) 2007 4 8 39 45 20532026 PMC2880945
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenThe safety and efficacy of lisdexamfetamine in patients aged 3-5 years has not been established.
“Further, it should be noted that the safety and efficacy of lisdexamfetamine in patients aged 3–5 years has not been established.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationIn that follow-up, lisdexamfetamine was well tolerated, and the only adverse effects reported by more than 5% of subjects were insomnia and irritability.
“Lisdexamfetamine was well tolerated, and the only adverse effects were insomnia and irritability, reported by more than 5% of the subjects.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] Findling RL Childress AC Krishnan S McGough JJ Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder CNS Spectr 2008 13 7 614 620 18622366 source
May combine two claims.
PremisecitationIn an open-label study of 40 adults treated with lisdexamfetamine for 12 weeks, Adler et al found a significant reduction in ADHD-RS-IV scores and a significant improvement on the Time-Sensitive ADHD Symptom Scale.
“In an open-label study of 40 adults treated with lisdexamfetamine for 12 weeks, Adler et al31 found a significant reduction in ADHD-RS-IV scores. Based on assessments using the Time-Sensitive ADHD Symptom Scale, they asked patients to rate their ADHD symptoms a few hours earlier, and a significant improvement was reported.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] Adler LA Lynch LR Shaw DM Effectiveness and duration of effect of open-label lisdexamfetamine dimesylate in adults with ADHD J Atten Disord 5 8 2013 [Epub ahead of print.] 23657761 source
May combine two claims.
PremisecitationIn Wigal et al small 4-week open-label trial, the duration of treatment emergent adverse events was similar between stimulant-naïve and stimulant-exposed children, but the stimulant-naïve group reported more adverse events including difficulty sleeping, abdominal pain, and hyperfocus.
“While the duration of the treatment emergent adverse events experienced in both groups was similar, the stimulant-naïve group reported more adverse events, including difficulty sleeping, abdominal pain, and “hyperfocus”.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Wigal SB Wong AA Jun A Stehli A Steinberg-Epstein R Lerner MA Adverse events in medication treatment-naïve children with attention-deficit/hyperactivity disorder: results from a small, controlled trial of lisdexamfetamine dimesylate J Child Adolesc Psychopharmacol 2012 22 2 149 156 22372513 source
May combine two claims.
PremisecitationIn a randomized placebo-controlled trial of 420 adults with ADHD, Adler et al found statistically significant improvements in ADHD-RS-IV and CGI scores for all doses of lisdexamfetamine (30-50 mg) compared with placebo, evident from the first week.
“In a randomized, placebo-controlled trial of 420 adult subjects with ADHD, Adler et al27 found statistically significant improvements in ADHD-RS-IV and CGI scores for all doses of lisdexamfetamine (30–50 mg) compared with placebo. These improvements were evident from the first week.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Adler LA Goodman DW Kollins SH Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder J Clin Psychiatry 2008 69 9 1364 1373 19012818 source
May combine two claims. The quote only partly states this claim.
PremisecitationIn Findling et al follow-up of 272 children, improvements in ADHD-RS-IV scores started at one week and were sustained throughout the 11-month dose-maintenance phase.
“Improvements in ADHD-RS-IV scores started at one week and were sustained throughout the study.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] Findling RL Childress AC Krishnan S McGough JJ Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder CNS Spectr 2008 13 7 614 620 18622366 source
May combine two claims.
PremisecitationIn that trial, there were no significant changes in the subjects' electrocardiograms, but there was a mild increase in heart rate of 4-5 beats per minute.
“There were no significant changes in the subjects’ electrocardiograms, but there was a mild increase in heart rate of 4–5 beats per minute.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Biederman J Krishnan S Zhang Y McGough JJ Findling RL Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study Clin Ther 2007 29 3 450 463 17577466 source
May combine two claims.
PremisecitationIn Giblin et al study of 24 children with ADHD aged 6-12 years, lisdexamfetamine was not associated with sleep disturbances on either subjective or objective measures, and sleep efficiency was slightly improved compared with placebo.
“Lisdexamfetamine was not associated with sleep disturbances on either subjective or objective measures, and sleep efficiency was reported as being slightly improved compared with the placebo group.24”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Giblin JM Strobel AL Effect of lisdexamfetamine dimesylate on sleep in children with ADHD J Atten Disord 2011 15 6 491 498 20574056 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMora et al suggest that impaired heart rate recovery may be an indicator of cardiovascular risk.
“Mora et al suggest that impaired heart rate recovery may be an indicator of cardiovascular risk.21”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Mora S Redberg RF Cui Y Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study JAMA 2003 24 290 12 1600 1607 14506119 source
May combine two claims.
PremisecitationIn Dupaul et al open-label study of 24 college students with ADHD, even though an 86% improvement in ADHD symptoms was reported, along with improvement in executive functioning and small changes in psychosocial functioning, there remained a gap compared with control subjects.
“Even though an 86% improvement in ADHD symptoms was reported, along with improvement in executive functioning and small changes in psychosocial functioning, there remained a gap in comparison with control subjects.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [39] Dupaul GJ Weyandt LL Rossi JS Double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in college students with ADHD J Atten Disord 2012 16 3 202 220 22166471 source
May combine two claims.
PremisecitationIn that trial, adverse effects were reported mainly during the first week of treatment and included decreased appetite, weight loss, insomnia, upper abdominal pain, headache, irritability, nausea, and vomiting; these resolved over the course of the study for the majority of subjects.
“Adverse effects were reported mainly during the first week of treatment, and included decreased appetite, weight loss, insomnia, upper abdominal pain, headache, irritability, nausea, and vomiting. These resolved over the course of the study for the majority of subjects.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] Biederman J Krishnan S Zhang Y McGough JJ Findling RL Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study Clin Ther 2007 29 3 450 463 17577466 source
May combine two claims.
PremisecitationIn that trial, 6% of subjects in the lisdexamfetamine group discontinued the drug owing to side effects, the most common being insomnia; palpitations, hypertension, and dyspnea were also more common in the treatment group than in the placebo group.
“Six percent of subjects in the lisdexamfetamine group discontinued the drug owing to side effects, the most common being insomnia. Palpitations, hypertension, and dyspnea were also more common in the treatment group than in the placebo group.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] Adler LA Goodman DW Kollins SH Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder J Clin Psychiatry 2008 69 9 1364 1373 19012818 source
May combine two claims.
PremisecitationIn Findling et al open-label 7-week dose-optimization study of 318 children, lisdexamfetamine was well tolerated and produced statistically significant improvements on ADHD-RS-IV, CGI, Parent Global Assessment, BRIEF, and EESC scales.
“Lisdexamfetamine was well tolerated throughout this study. Statistically significant (P < 0.001) improvements on the ADHD-RS-IV scale were found, as well as improvements on the CGI, Parent Global Assessment, Behavior Rating Inventory of Executive Function (BRIEF), and Expression and Emotion Scale for Children (EESC) scales.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] Findling RL Ginsberg LD Jain R Gao J Effectiveness, safety, and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: an open-label, dose-optimization study J Am Acad Child Adolesc Psychiatry 2009 19 6 649 662 20035583 source
May combine two claims.
InterpretationcitationUse of lisdexamfetamine in patients with ADHD may improve functioning in academic and work environments, but the level of functioning may still not be equal to that of their non-ADHD peers.
“Use of lisdexamfetamine in patients with ADHD may improve functioning in academic and work environments, but the level of functioning may still not be equal to that of their non-ADHD peers.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn that study, a 12-year-old girl with a prior history of intermittent syncope experienced a syncopal episode on lisdexamfetamine 60 mg that was considered a serious adverse event, but she completed the study successfully.
“The first occurred in a 12-year-old girl with a prior history of intermittent syncope who experienced a syncopal episode on lisdexamfetamine 60 mg that was considered a serious adverse event, but she went on to complete the study successfully.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] Findling RL Ginsberg LD Jain R Gao J Effectiveness, safety, and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: an open-label, dose-optimization study J Am Acad Child Adolesc Psychiatry 2009 19 6 649 662 20035583 source
May combine two claims.
PremisecitationThis growth delay was associated with the children being stimulant-naïve, heavier and taller on entry into the study, and having greater cumulative exposure to medication.
“This delay was associated with the children being stimulant-naïve, heavier and taller on entry into the study, and having “greater cumulative exposure” to medication.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] Faraone S V Spencer TJ Kollins SH Glatt SJ Effects of lisdexamfetamine dimesylate treatment for ADHD on growth J Am Acad Child Adolesc Psychiatry 2010 49 1 24 32 20215923 source
May combine two claims.
PremisecitationIn Biederman et al randomized controlled trial of 61 ADHD subjects aged 18-26 years, lisdexamfetamine-treated patients had a lower rate of collisions and faster reaction time compared with placebo in a validated driving simulation paradigm.
“In a randomized, controlled trial involving 61 ADHD subjects aged 18–26 years, Biederman et al40 showed that lisdexamfetamine-treated patients had a lower rate of collisions and faster reaction time in comparison with placebo in a validated driving simulation paradigm.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [40] Biederman J Fried R Hammerness P The effects of lisdexamfetamine dimesylate on the driving performance of young adults with ADHD: a randomized, double-blind, placebo-controlled study using a validated driving simulator paradigm J Psychiatr Res 2012 46 4 484 491 22277301 source
May combine two claims.
PremisecitationIn Hammerness et al open-label study of 15 patients, transthoracic echocardiography and cardiopulmonary exercise testing showed changes in resting left ventricular systolic function and diastolic indices on treatment with lisdexamfetamine; however, these changes were not in the direction of cardiomyopathy and there were no major changes in cardiac function at maximal exertion.
“Transthoracic echocardiography and cardiopulmonary exercise testing showed changes in resting left ventricular systolic function and diastolic indices on treatment with lisdexamfetamine. However, these changes were not in the direction of cardiomyopathy and there were no major changes in cardiac function at maximal exertion.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [20] Hammerness P Zusman R Systrom D A cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder World J Biol Psychiatry 2013 14 4 299 306 22559155 source
May combine two claims.
PremisecitationIn that study, lisdexamfetamine had a smooth medication effect throughout the day, with fewer rebound symptoms.
“They also found that lisdexamfetamine had a smooth medication effect throughout the day, with fewer rebound symptoms.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] Adler LA Lynch LR Shaw DM Effectiveness and duration of effect of open-label lisdexamfetamine dimesylate in adults with ADHD J Atten Disord 5 8 2013 [Epub ahead of print.] 23657761 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn that study, a 7-year-old boy with an implanted loop recorder after a prior near-drowning incident had a sinus arrest of 6 seconds while on lisdexamfetamine 30 mg; it was determined to be unrelated to lisdexamfetamine and he was discontinued from the study.
“The second serious adverse event occurred in a 7-year-old boy with an implanted loop recorder after a prior near-drowning incident, who was noted to have a sinus arrest of 6 seconds while on lisdexamfetamine 30 mg. Although this was determined to be unrelated to lisdexamfetamine, the subject was discontinued from the study.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] Findling RL Ginsberg LD Jain R Gao J Effectiveness, safety, and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: an open-label, dose-optimization study J Am Acad Child Adolesc Psychiatry 2009 19 6 649 662 20035583 source
May combine two claims.
PremisecitationIn a 4-week randomized controlled trial of 314 adolescents with ADHD, lisdexamfetamine did well across all doses (30 mg, 50 mg, and 70 mg) compared with placebo, as evidenced by improvement in scores on ADHD-RS-IV, CGI, and Youth Quality of Life-Research Version.
“In a 4-week, randomized, controlled trial26 involving 314 adolescents with ADHD who were randomized to receive placebo or to be part of a forced titration arm of lisdexamfetamine (30 mg, 50 mg, and 70 mg), lisdexamfetamine did well across all of the doses in comparison with placebo, as evidenced by improvement in scores on the ADHD-RS-IV, CGI, and Youth Quality of Life-Research Version.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Findling RL Childress AC Cutler AJ Efficacy and safety of lisdexamfetamine dimesylate in adolescents with attention-deficit/hyperactivity disorder J Am Acad Child Adolesc Psychiatry 2011 50 4 395 405 21421179 source
May combine two claims.
PremisecitationIn Biederman et al Phase III trial of 290 children aged 6-12 years with ADHD, compared with placebo, ADHD-RS-IV score reductions were 4-5-fold greater in the lisdexamfetamine groups, with the largest reductions recorded in the 70 mg lisdexamfetamine group.
“Compared with the placebo group, ADHD Rating Scale Version IV (ADHD-RS-IV) score reductions were 4–5-fold (P < 0.001) greater in the lisdexamfetamine groups, with the largest reductions recorded in the 70 mg lisdexamfetamine group.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] Biederman J Krishnan S Zhang Y McGough JJ Findling RL Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study Clin Ther 2007 29 3 450 463 17577466 source
May combine two claims.
PremisecitationIn that study, insomnia was a common adverse effect, one patient could not tolerate a dose increase for this reason, and six patients withdrew from the study due to side effects.
“However, insomnia was a common adverse effect and one patient could not tolerate a dose increase for this reason. It was also reported that six patients withdrew from the study due to side effects.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] Adler LA Lynch LR Shaw DM Effectiveness and duration of effect of open-label lisdexamfetamine dimesylate in adults with ADHD J Atten Disord 5 8 2013 [Epub ahead of print.] 23657761 source
Probably not a substantial claim: may not pass S4 (based).
Premisenone givenMost such studies exclude subjects with preexisting cardiac morbidity.
“Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationIn Jasinski et al randomized three-arm crossover study of intravenous lisdexamfetamine 25 mg or 50 mg, immediate-release dextroamphetamine 10 mg or 20 mg, or placebo in 12 healthy subjects with a history of stimulant abuse, lisdexamfetamine was not different from placebo in liking effects whereas immediate-release dextroamphetamine was associated with euphoria within 15 minutes.
“A randomized, three-arm crossover study42 of intravenous administration of lisdexamfetamine 25 mg or 50 mg, immediate-release dextroamphetamine 10 mg or 20 mg, or placebo in 12 healthy subjects with a history of stimulant abuse showed that lisdexamfetamine was not different from placebo in “liking effects” whereas immediate-release dextroamphetamine was associated with euphoria within 15 minutes.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [42] Jasinski DR Krishnan S Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers J Psychopharmacol 2009 23 4 410 418 18635707 source
May combine two claims.
PremisecitationIn that study, lisdexamfetamine 50 mg and 100 mg were similar to placebo on liking, but lisdexamfetamine 150 mg was equivalent to 40 mg dextroamphetamine.
“The 50 mg and 100 mg doses of lisdexamfetamine were similar to placebo; however, the 150 mg dose was equivalent to the 40 mg dose of dextroamphetamine.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [43] Weber J Siddiqui MA Lisdexamfetamine dimesylate: in attention-deficit hyperactivity disorder in adults CNS Drugs 2009 23 5 419 425 19453202 source
May combine two claims.
PremisecitationShort-acting stimulant formulations are limited by the need for multiple dosing, the stigma of the school dose, and the higher risk of drug diversion.
“However, use of short-acting formulations is limited by the need for multiple dosing, the stigma of the school dose, and the higher risk of drug diversion.6”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Cascade E Kalali AH Weisler RH Short-acting versus long-acting medications for the treatment of ADHD Psychiatry (Edgmont) 2008 5 8 24 27 19727272 PMC2695738
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenAdverse effects such as decrease in sleep, loss of appetite, and others have been reported with lisdexamfetamine use, just as with other stimulant formulations.
“Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationLisdexamfetamine has shown to be safe, well tolerated, and efficacious in the management of ADHD in child-adolescent and adult populations.
“Lisdexamfetamine has shown to be safe, well tolerated, and efficacious in the management of ADHD in the child-adolescent and adult populations.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationPharmacotherapy for ADHD is efficacious and cost-effective compared with behavioral therapy alone and compared with combined use of behavioral and pharmacotherapy.
“Pharmacotherapy for ADHD is an efficacious as well as cost-effective treatment measure for ADHD when compared with behavioral therapy alone and compared with combined use of behavioral and pharmacotherapy.45”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [45] Wu EQ Hodgkins P Ben-Hamadi R Cost effectiveness of pharmacotherapies for attention-deficit hyperactivity disorder: a systematic literature review CNS Drugs 2012 26 7 581 600 22712698 source
May combine two claims.
Interpretationown dataLisdexamfetamine has a smooth onset of action, exerts its action up to 13 hours, and may have less rebound symptoms.
“It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms.”
Quote in the paperSubstantial claim
The paper relies on this without support.
Patients with ADHD have a high risk for comorbidity involving substance misuse disorders.
“Patients with ADHD have a high risk for comorbidity involving substance misuse disorders, so it is imperative to evaluate the potential for an ADHD medication to lead to abuse or dependence.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In contrast to other amphetamines, LDX has a long-acting prodrug formulation requiring red blood cell enzymatic conversion into the active form of amphetamine, reducing side effects and abuse potential.
“Moreover, in contrast to other amphetamines, LDX has a long-acting prodrug formulation requiring red blood cell enzymatic conversion into the active form of amphetamine, reducing side effects and abuse potential [42].”
From Treating new-onset cognitive complaints after risk-reducing salpingo-oophorectomy: A randomized controlled crossover trial of lisdexamfetamine (2024) · cites this paper as [42]
The Introduction and Pharmacologic aspects sections describe LDX as a longer-acting prodrug converted to dextroamphetamine by hydrolysis in red blood cells. But the paper says it *may* cause fewer adverse reactions than mixed-amphetamine extended-release salts and that its lower abuse potential is hypothesized, rather than establishing that the formulation reduces both risks. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLisdexamfetamine has less potential for abuse and diversion compared with other stimulants.
“As a prodrug, LDX needs an enzyme in red blood cells to convert to the active form of amphetamine; therefore, it has less potential for abuse and diversion, and longer effect, as compared with other stimulants.14,15”
From Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD (2014) · cites this paper as [15]
The Abstract says LDX may have somewhat less potential for abuse and diversion, and Pharmacologic aspects says its prodrug formulation may lower abuse potential. The claim presents that tentative comparison as an established fact; Potential for misuse and abuse also cautions that diversion and abuse remain risks. (LLM, conf=0.87)
Experimental — accuracy not yet measuredLisdexamfetamine has a longer effect compared with other stimulants.
“As a prodrug, LDX needs an enzyme in red blood cells to convert to the active form of amphetamine; therefore, it has less potential for abuse and diversion, and longer effect, as compared with other stimulants.14,15”
From Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD (2014) · cites this paper as [15]
The Introduction describes lisdexamfetamine as a longer-acting formulation, and the Abstract reports effects lasting up to 13 hours. Neither establishes that its effects last longer than those of other long-acting stimulants; the Safety and tolerability section notes a lack of head-to-head comparisons with comparable agents. Page numbers were not provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDextroamphetamine blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and directly increases the release of these monoamines extraneuronally.
“Like other stimulants, dextroamphetamine blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and directly increases the release of these monoamines extraneuronally.9”
From Comparative efficacy, acceptability, and tolerability of lisdexamfetamine in child and adolescent ADHD: a meta-analysis of randomized, controlled trials (2015) · cites this paper as [9]
LDX requires an enzyme in red blood cells to be converted to active amphetamine, so it tends to have less potential for drug abuse and diversion and has a relatively long-acting property.
“Since LDX requires an enzyme in red blood cells to be converted to the active form of amphetamine, it tends to have less potential for drug abuse and diversion, and has a relatively long-acting property.8,9”
From Comparative efficacy, acceptability, and tolerability of lisdexamfetamine in child and adolescent ADHD: a meta-analysis of randomized, controlled trials (2015) · cites this paper as [9]
Efficacy of LDX is explained by its active metabolite, dextroamphetamine.
“The efficacy of LDX in such patients is explained by its active metabolite, dextroamphetamine.”
From Comparative efficacy, acceptability, and tolerability of lisdexamfetamine in child and adolescent ADHD: a meta-analysis of randomized, controlled trials (2015) · cites this paper as [9]
Lisdexamfetamine requires an enzyme in red blood cells to convert to the active form of amphetamine.
“As a prodrug, LDX needs an enzyme in red blood cells to convert to the active form of amphetamine; therefore, it has less potential for abuse and diversion, and longer effect, as compared with other stimulants.14,15”
From Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD (2014) · cites this paper as [15]
The efficacy of lisdexamfetamine in adult ADHD may be explained by its metabolite dextroamphetamine, which blocks reuptake of norepinephrine and dopamine into the presynaptic neuron and directly increases release of these monoamines extraneuronally.
“The efficacy of LDX in adult ADHD may be explained by its metabolite, dextroamphetamine, which blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and directly increases the release of these monoamines extraneuronally, similar to other psychostimulants.15”
From Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD (2014) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
College-student study described as both open-label and double-blind
MinorThe text calls the Dupaul et al study open-label, while the cited reference describes the same study as double-blind and placebo-controlled.
“In an open-label study, Dupaul et al39 examined 24 college students with ADHD”
“39. Dupaul GJ Weyandt LL Rossi JS Double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in college students with ADHD”
Cites
The worldwide prevalence of ADHD: a systematic review and metaregression analysis
Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.6.942 · Cited by 5,346 · cited 2× · see citing works
“These can be used as either monotherapy, as an adjunct to another medication, or more recently, as combinations.(3,4) Bupropion and modafinil are two other nonstimulant medications that have also been studied in ADHD, but have had limited success.”
BackgroundMora, S., Redberg, R. F., Cui, Y., Whiteman, M. K., Flaws, J. A., Sharrett, A. R., & Blumenthal, R. S. (2003) · JAMA · doi:10.1001/jama.290.12.1600 · Cited by 579 · cited 1× · see citing works
“Mora et al suggest that impaired heart rate recovery may be an indicator of cardiovascular risk.(21) In another study by Findling et al, 318 children (6–12 years) with ADHD entered an open-label, 7-week, dose-optimization study with a starting lisdexamfetamine dose of 20 mg, with 10 mg dose increments at weekly interv…”
Biederman, J., Krishnan, S., Zhang, Y., McGough, J. J., & Findling, R. L. (2007) · Clinical Therapeutics · doi:10.1016/s0149-2918(07)80083-x · Cited by 404 · cited 1× · see citing works
“A forced-dose, randomized, controlled Phase III trial conducted by Biederman et al 18 included 290 children (6–12 years) with ADHD who were randomized into four cohorts.”
Biederman, J., Boellner, S. W., Childress, A., Lopez, F. A., Krishnan, S., & Zhang, Y. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.04.015 · Cited by 356 · see citing works
Treatment of Attention-Deficit/Hyperactivity Disorder: Overview of the Evidence
Brown, R. T., Amler, R. W., Freeman, W. S., Perrin, J. M., Stein, M. T., Feldman, H. M., Pierce, K., & Wolraich, M. L. (2005) · PEDIATRICS · doi:10.1542/peds.2004-2560 · Cited by 331 · cited 1× · see citing works
“These can be used as either monotherapy, as an adjunct to another medication, or more recently, as combinations.(3,4) Bupropion and modafinil are two other nonstimulant medications that have also been studied in ADHD, but have had limited success.”
Birnbaum, H. G., Kessler, R. C., Lowe, S. W., Secnik, K., Greenberg, P. E., Leong, S. A., & Swensen, A. R. (2005) · Current Medical Research and Opinion · doi:10.1185/030079904x20303 · Cited by 237 · see citing works
Adler, L. A., Goodman, D. W., Kollins, S. H., Weisler, R. H., Krishnan, S., Zhang, Y., & Biederman, J. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0903 · Cited by 218 · cited 3× · see citing works
“Weisler et al 28 recruited 349 patients from the study by Adler et al 27 for a 12-month, follow-up study, which was completed by 191 patients.”
Turgay, A., Goodman, D. W., Asherson, P. J., Lasser, R. A., Babcock, T. F., Pucci, M. L., Barkley, R. A., & ADHD Transition Phase Model Working Group (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.10m06628 · Cited by 205 · cited 1× · see citing works
“Symptoms of ADHD often begin in early childhood, and persist well into adolescence and adulthood in about 50%–60% of individuals.(1) ADHD is often associated with comorbid psychiatric disorders, such as oppositional defiant disorder, conduct disorder, and childhood mood and anxiety disorders.”
BackgroundAbsorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
Pennick (2010) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s9749 · Cited by 170 · cited 1× · see citing works
“Lisdexamfetamine enters the portal circulation unchanged via the peptide protein transporter system, and the covalent linkage between lysine and dextroamphetamine is broken down by hydrolysis in the red blood cell.(10) Krishnan and Moncrief demonstrated that lisdexamfetamine is not metabolized by the hepatic cytochrom…”
BackgroundWigal, T., Brams, M., Gasior, M., Gao, J., Squires, L., Giblin, J., & 316 Study Group (2010) · Behavioral and Brain Functions · doi:10.1186/1744-9081-6-34 · Cited by 136 · see citing works
Findling, R. L., Childress, A. C., Cutler, A. J., Gasior, M., Hamdani, M., Ferreira-Cornwell, M. C., & Squires, L. (2011) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2011.01.007 · Cited by 120 · see citing works
the 311 Study Group, Wigal, S. B., Kollins, S. H., Childress, A. C., & Squires, L. (2009) · Child and Adolescent Psychiatry and Mental Health · doi:10.1186/1753-2000-3-17 · Cited by 112 · see citing works
Jasinski, D., & Krishnan, S. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881108093841 · Cited by 100 · see citing works
Weisler, R., Young, J., Mattingly, G., Gao, J., Squires, L., Adler, L., & 304 Study Group (2009) · CNS Spectrums · doi:10.1017/s1092852900024056 · Cited by 94 · cited 1× · see citing works
“Weisler et al 28 recruited 349 patients from the study by Adler et al 27 for a 12-month, follow-up study, which was completed by 191 patients.”
Findling, R. L., Childress, A. C., Krishnan, S., & McGough, J. J. (2008) · CNS Spectrums · doi:10.1017/s1092852900016898 · Cited by 90 · cited 3× · see citing works
“Sixty seven out of 129 subjects in the study by Wigal et al 33 and 83 subjects out of 318 participants in the study by Findling et al 22 received treatment with methylphenidate in the 6 months preceding the lisdexamfetamine trail, and these subjects were included in the subgroup analysis.”
DuPaul, G. J., Weyandt, L. L., Rossi, J. S., Vilardo, B. A., O’Dell, S. M., Carson, K. M., Verdi, G., & Swentosky, A. (2012) · Journal of Attention Disorders · doi:10.1177/1087054711427299 · Cited by 86 · see citing works
Krishnan, S., & Zhang, Y. (2008) · The Journal of Clinical Pharmacology · doi:10.1177/0091270007310381 · Cited by 73 · cited 1× · see citing works
“Time to reach maximal concentration was delayed by one hour when 70 mg of lisdexamfetamine was administered with food compared with the fasting state in healthy adult volunteers, but there was no change in C max levels.(14) Absorption was not significantly affected whether lisdexamfetamine was administered with or wit…”
MethodBoellner, S. W., Stark, J. G., Krishnan, S., & Zhang, Y. (2010) · Clinical Therapeutics · doi:10.1016/j.clinthera.2010.02.011 · Cited by 72 · cited 1× · see citing works
“A dose-proportional increase in the area under the curve and C max of dextroamphetamine with low interpatient variability was demonstrated in children with ADHD using doses of 30 mg, 50 mg, and 70 mg.(15) Oral and intranasal administration of lisdexamfetamine in healthy adult volunteers showed a similar C max , area u…”
BackgroundReview of ADHD Pharmacotherapies: Advantages, Disadvantages, and Clinical Pearls
Daughton, J., & Kratochvil, C. J. (2009) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e318197748f · Cited by 70 · cited 1× · see citing works
“Bupropion and modafinil are two other nonstimulant medications that have also been studied in ADHD, but have had limited success.(5) The use of stimulants for inattention and hyperactivity symptoms was first described in the 1930s and was revisited in the 1960s with the frequent use of short-acting stimulant formulati…”
BackgroundMora, S., Redberg, R. F., & Yadong, C. (2004) · ACC Current Journal Review · doi:10.1016/j.accreview.2003.10.032 · Cited by 63 · see citing works
Biederman, J., Fried, R., Hammerness, P., Surman, C., Mehler, B., Petty, C. R., Faraone, S. V., Miller, C., Bourgeois, M., Meller, B., et al. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.01.007 · Cited by 60 · see citing works
Wu, E. Q., Hodgkins, P., Ben-Hamadi, R., Setyawan, J., Xie, J., Sikirica, V., Du, E. X., Yan, S. Y., & Erder, M. H. (2012) · CNS Drugs · doi:10.2165/11633900-000000000-00000 · Cited by 58 · cited 1× · see citing works
“Pharmacotherapy for ADHD is an efficacious as well as cost-effective treatment measure for ADHD when compared with behavioral therapy alone and compared with combined use of behavioral and pharmacotherapy.(45) More research is required to study the individual pharmacotherapeutic options, including nonstimulants.”
MethodMultiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers
Krishnan, S. M., & Stark, J. G. (2008) · Current Medical Research and Opinion · doi:10.1185/030079908x242737 · Cited by 55 · cited 1× · see citing works
“In healthy adult volunteers, a steady-state concentration of dextroamphetamine following administration of lisdexamfetamine 70 mg was achieved by day 5.(12) Consistent levels of mean peak plasma concentration (C max ) and area under the curve for”
BackgroundKrishnan, S., & Moncrief, S. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.011973 · Cited by 50 · cited 1× · see citing works
“Krishnan and Moncrief demonstrated that lisdexamfetamine is not metabolized by the hepatic cytochrome P450 system, so lisdexamfetamine has a low potential for drug–drug interactions.(11) The pharmacodynamics of dextroamphetamine include reuptake inhibition of monoamines and also direct stimulation of release of dopami…”
BackgroundFindling, R. L., Ginsberg, L. D., Jain, R., & Gao, J. (2009) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2008.0165 · Cited by 45 · cited 1× · see citing works
“In another study by Findling et al, 318 children (6–12 years) with ADHD entered an open-label, 7-week, dose-optimization study with a starting lisdexamfetamine dose of 20 mg, with 10 mg dose increments at weekly intervals up to a maximum dose of 70 mg based on response following a 2-week washout period.(22) Lisdexamfe…”
MethodBrams, M., Weisler, R., Findling, R. L., Gasior, M., Hamdani, M., Ferreira-Cornwell, M. C., & Squires, L. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11m07430 · Cited by 41 · see citing works
Effects of Lisdexamfetamine Dimesylate Treatment for ADHD on Growth
Faraone, S. V., Spencer, T. J., Kollins, S. H., & Glatt, S. J. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-201001000-00006 · Cited by 39 · see citing works
Effect of Lisdexamfetamine Dimesylate on Sleep in Children With ADHD
Giblin, J. M., & Strobel, A. L. (2011) · Journal of Attention Disorders · doi:10.1177/1087054710371195 · Cited by 38 · cited 1× · see citing works
“Lisdexamfetamine was not associated with sleep disturbances on either subjective or objective measures, and sleep efficiency was reported as being slightly improved compared with the placebo group.(24) Another common concern with stimulant medications in children is growth retardation.”
Result(2012) · Europe PMC (PubMed Central) · Cited by 37 · see citing works
Ermer, J. C., Dennis, K., Haffey, M. B., Doll, W. J., Sandefer, E. P., Buckwalter, M., Page, R. C., Diehl, B., & Martin, P. T. (2011) · Clinical Drug Investigation · doi:10.2165/11588190-000000000-00000 · Cited by 35 · cited 1× · see citing works
“Oral and intranasal administration of lisdexamfetamine in healthy adult volunteers showed a similar C max , area under the curve, and time to reach maximal concentration, with low intersubject variability and similar tolerability rates for both routes of administration.(16)”
BackgroundShort-acting versus Long-acting Medications for the Treatment of ADHD.
(2008) · Europe PMC (PubMed Central) · Cited by 30 · see citing works
Brown, T. E., Brams, M., Gao, J., Gasior, M., & Childress, A. (2010) · Postgraduate Medicine · doi:10.3810/pgm.2010.09.2196 · Cited by 29 · cited 1× · see citing works
“Other research that examined the efficacy of lisdexamfe-tamine in an academic or work environment includes a small open-label study Brown et al 37 that showed a statistically significant improvement in executive functioning in ADHD subjects treated with lisdexamfetamine using the Brown…”
Attention Deficit/Hyperactivity Disorder
Talaeı, A., Mokhber, N., Abdollahian, E., Bordbar, M. R. F., & Salari, E. (2009) · Journal of Attention Disorders · doi:10.1177/1087054708329886 · Cited by 26 · see citing works
Wigal, S. B., Wong, A. A., Jun, A., Stehli, A., Steinberg-Epstein, R., & Lerner, M. A. (2012) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2010.0095 · Cited by 26 · see citing works
Lisdexamfetamine dimesylate: the first prodrug stimulant.
(2007) · PubMed Central · Cited by 24 · see citing works
Young, J. L. (2013) · Psychiatry Research · doi:10.1016/j.psychres.2012.09.007 · Cited by 23 · see citing works
Turgay, A., Ginsberg, L., Sarkis, E., Jain, R., Adeyi, B., Gao, J., Dirks, B., Babcock, T., Scheckner, B., Richards, C., et al. (2010) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2009.0110 · Cited by 23 · cited 6× · see citing works
“In another open-label, dose-optimization study of lisdexamfetamine 30–70 mg in 26 children with ADHD, Wigal et al 34 demonstrated improvements in rate, accuracy, and comprehension measures on the Gray Oral Reading Test-4 performed at baseline and after 4–5 weeks of treatment in a “modified laboratory school” setting.”
InfluentialEffectiveness and Duration of Effect of Open-Label Lisdexamfetamine Dimesylate in Adults With ADHD
Adler, L. A., Lynch, L. R., Shaw, D. M., Wallace, S. P., O’Donnell, K. E., Ciranni, M. A., Briggie, A. M., & Faraone, S. V. (2017) · Journal of Attention Disorders · doi:10.1177/1087054713485421 · Cited by 23 · see citing works
Ermer, J. C., Haffey, M. B., Doll, W. J., Martin, P., Sandefer, E. P., Dennis, K., Corcoran, M., Trespidi, L., & Page, R. C. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.040691 · Cited by 22 · cited 1× · see citing works
“dextroamphetamine were recorded when healthy adult volunteers were administered lisdexamfetamine 50 mg using oral capsules and InteliSiteTM delivery capsules (Casper Associates, Raleigh, NC, USA) designed to release the drug selectively in selected small intestinal regions.(13) Time to reach maximal concentration was…”
MethodA cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder
Hammerness, P., Zusman, R., Systrom, D., Surman, C., Baggish, A., Schillinger, M., Shelley-Abrahamson, R., & Wilens, T. E. (2013) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2012.678884 · Cited by 15 · cited 1× · see citing works
“Interestingly, heart rate recovery was elevated by 4 beats per minute in this study.(20) Mora et al suggest that impaired heart rate recovery may be an indicator of cardiovascular risk.”
BackgroundWigal, S. B., Maltas, S., Crinella, F., Stehli, A., Steinhoff, K., Lakes, K., & Schuck, S. (2012) · Journal of Attention Disorders · doi:10.1177/1087054710378008 · Cited by 14 · cited 7× · see citing works
“In another open-label, dose-optimization study of lisdexamfetamine 30–70 mg in 26 children with ADHD, Wigal et al 34 demonstrated improvements in rate, accuracy, and comprehension measures on the Gray Oral Reading Test-4 performed at baseline and after 4–5 weeks of treatment in a “modified laboratory school” setting.”
InfluentialLisdexamfetamine Dimesylate: In Attention-Deficit Hyperactivity Disorder in Adults
Weber, J., & Siddiqui, M. A. A. (2009) · CNS Drugs · doi:10.2165/00023210-200923050-00005 · Cited by 13 · see citing works
Effects of Lisdexamfetamine Dimesylate Treatment for ADHD on Growth
Faraone, S. V., Spencer, T. J., Kollins, S. H., & Glatt, S. J. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2009.10.003 · Cited by 13 · see citing works
Madaan, V., & Domnitei (2010) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s3328 · Cited by 12 · cited 1× · see citing works
“From a typical initial dose of 30 mg/day, it can be uptitrated based on clinical response and tolerability to a maximum of 70 mg/day in weekly increments of 10–20 mg.(8) Lisdexamfetamine is currently the only stimulant prodrug available, with a unique formulation that may help to lower the potential for abuse, toxicit…”
BackgroundSelf-citationLisdexamfetamine dimesylate for childhood ADHD
Madaan, V. (2008) · Drugs of Today · doi:10.1358/dot.2008.44.5.1215724 · Cited by 11 · see citing works
Self-citationKatic, A., Ginsberg, L., Jain, R., Adeyi, B., Dirks, B., Babcock, T., Scheckner, B., Richards, C., Lasser, R., Turgay, A., et al. (2012) · Journal of Attention Disorders · doi:10.1177/1087054710389990 · Cited by 10 · cited 2× · see citing works
“In a post hoc analysis of this 7-week, open-label lisdexamfetamine study, Katic et al 36 used the clinically meaningful change and clinically significant/ reliable change categories derived from the EESC to show that there was no deterioration in emotional expression in a majority of subjects when taking lisdexamfetam…”
Jain, R., Babcock, T., Burtea, T., Dirks, B., Adeyi, B., Scheckner, B., Lasser, R., Renna, J., & Duncan, D. (2013) · Advances in Therapy · doi:10.1007/s12325-013-0027-2 · Cited by 9 · see citing works
Donovan, S. J., & Levin, F. R. (2011) · The American Journal of Drug and Alcohol Abuse · doi:10.3109/00952990.2011.569805 · Cited by 5 · cited 1× · see citing works
“In an open-label lisdexamfetamine study with an innovative design, Donovan and Levin 41 treated eight adolescents with ADHD whose older siblings had substance misuse problems.”
Mack, A. H. (2012) · Yearbook of Psychiatry and Applied Mental Health · doi:10.1016/j.ypsy.2011.08.095 · Cited by 5 · see citing works
Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers
Krishnan, S. M., & Stark, J. G. (2008) · Current Medical Research and Opinion · doi:10.1185/030079907x242737 · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 51 references couldn’t be matched to a known paper.
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Epilepsy and Attention Deficit Hyperactivity Disorder: Connection, Chance, and Challenges
Fan, H., Chiang, K.-L., Chang, K., Chen, C., & Tsai, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065270 · Cited by 36 · see citing works
Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD
Maneeton, B., Maneeton, N., Suttajit, S., Reungyos, J., Srisurapanont, M., & Martin, S. (2014) · Drug Design, Development and Therapy · doi:10.2147/dddt.s68393 · Cited by 27 · see citing works
“The efficacy of LDX in adult ADHD may be explained by its metabolite, dextroamphetamine, which blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and directly increases the release of these monoamines extraneuronally, similar to other psychostimulants.(15) Based on the prospective study of…”
A Review of Psychostimulants for Adults With Depression.
Pary, R., Scarff, J. R., Jijakli, A., TOBIAS, C. R., & Lippmann, S. (2015) · Europe PMC (PubMed Central) · Cited by 24 · see citing works
Maneeton, N., Maneeton, B., Likhitsatian, S., Suttajit, S., Narkpongphun, A., Srisurapanont, M., & Woottiluk, P. (2015) · Drug Design, Development and Therapy · doi:10.2147/dddt.s79071 · Cited by 23 · see citing works
“Like other stimulants, dextroamphetamine blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and directly increases the release of these monoamines extraneuronally.(9) Cardiovascular effect is another concern in the use of stimulants in the treatment of child and adolescent ADHD.”
Moderator Role of Monitoring in the Inhibitory Control of Adolescents With ADHD
Ramos-Galarza, C., & Pérez-Salas, C. (2018) · Journal of Attention Disorders · doi:10.1177/1087054718776478 · Cited by 17 · see citing works
Najib, J. S., Didenko, E., Meleshkina, D., Yusupov, K., Maw, K., Ramnarain, J., & Tabassum, M. (2020) · Current Medical Research and Opinion · doi:10.1080/03007995.2020.1815002 · Cited by 12 · see citing works
New frontiers in pharmacological treatment of attention-deficit hyperactivity disorder
Noah, A. A., & Sedky, H. E. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04328-z · Cited by 10 · see citing works
“This pharmacokinetic property makes lisdexamfetamine a potentially safer option among ampheta-mines for ADHD treatment (Madaan et al. 2013).”
Metcalf, C. A., Page, C. E., Stocker, B. O. S., Johnson, R. L., Duffy, K. A., Sammel, M. D., Loughead, J., & Epperson, C. N. (2024) · Gynecologic Oncology · doi:10.1016/j.ygyno.2024.07.689 · Cited by 7 · see citing works
The use of lisdexamfetamine dimesylate for the treatment of ADHD and other psychiatric disorders
Roncero, C., & Alvarez, E. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2014.932691 · Cited by 7 · see citing works
“LDX is not metabolized by the hepatic cytochrome P450 system, so LDX has a low potential for drug–drug interaction [23].”
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Clinical Practice Guideline for Patients with Attention Deficit/Hyperactivity Disorder
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Drug Development for New Psychiatric Drug Therapies
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Experiencia en la utilización de lisdexanfetamina en el manejo del TDAH de niños y adolescentes
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Acne associated with lisdexamfetamine
Tung, H. Y., & Bunker, C. B. (2023) · JEADV Clinical Practice · doi:10.1002/jvc2.317
Mendes, T. C., Teixeira, P. T. F., Leonhardt, R. M., Lima, T. A. D. C. F., & de Lima, C. (2025) · Revista Brasileira de Educação Médica · doi:10.1590/1981-5271v49.3-2024-0093
Singer, D. P., & Kothari, P. M. (2026) · Cureus · doi:10.7759/cureus.110860
“Soon after, our patient reported jitteriness and tachycardia on 60 mg. Noting that stimulants have individual therapeutic windows [8], that the adverse effects were currently exceeding the benefit, that cardiovascular safety must be prioritized, and that we should have more room to taper her…”
- Authors
- Madaan, V., Kolli, V., Bestha, D., & Shah, M.
- Affiliations
- University of Virginia Health System (US)
- University of Virginia (US)
- ORCID
- Kolli, Venkata
- Venue
- Neuropsychiatric Disease and Treatment
- Publisher
- Informa UK Limited
- Published
- 2013-07
- Volume
- 9
- Pages
- 977
- ISSN
- 1176-6328 (ISSN-L)
- PMC
- PMC3726586
- OpenAlex
- W2090189264
- Cited by
- 19
- References
- 51
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2020: 1 · 2018: 2 · 2016: 2 · 2015: 2 · 2014: 3
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neuropsychiatric Disease and Treatment (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroethics, Human Enhancement, Biomedical Innovations
- Keywords
- lisdexamfetamine, attention deficit hyperactivity disorder, long-acting stimulants, stimulant side effects, sleep reduction, appetite loss, abuse liability, executive function
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