Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD
Open accessAbstract
BACKGROUND: Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD). OBJECTIVES: This systematic review was undertaken to summarize LDX efficacy, acceptability, and tolerability in adult ADHD. All randomized controlled trials (RCTs) of lisdexamfetamine compared with placebo were included for synthesis. Clinical trials published between January 1991 and January 2014 were evaluated. METHODS: The database of MEDLINE(®), EMBASE™, CINAHL(®), PsycINFO(®) and Cochrane Controlled Trials Register were searched in January 2014. Studies were also searched in ClinicalTrials.gov and the EU Clinical Trials Register database. Study eligibility criteria, participants, and interventions were considered. All RCTs of LDX vs placebo reporting final results of: 1) severity of ADHD symptoms and executive function deficit, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events were included. The language of the papers was not restricted. All abstracts of studies gathered from the database were examined. After excluding irrelevant trials, the full text version of relevant studies were assessed and extracted for outcomes of interest. Examination of risks of bias, based on the Cochrane bias assessment, was carried out. The efficacy outcomes consisted of the mean end point or change scores for ADHD rating scales, the response rate, and the remission rate. The overall discontinuation rate and the discontinuation rate due to adverse events were measured for acceptability and tolerability, respectively. A random effect model was applied for the synthesis of relative risks (RRs), and weighted mean differences or standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: A total of 806 final study or safety participants were included. The dosage of lisdexamfetamine was 30 to 70 mg/day. The pooled mean scores of mean change and mean end point scores between LDX- and placebo-treated groups also had a significant difference (SMD [95% CI] of -0.97 [-1.15, -0.78], I(2)=18%). The pooled response rates for adult ADHD between the two groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I(2)=0%). Based on the Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A), the pooled end point mean scores for the Global Executive Composite (GEC) for the LDX-treated groups was greater than that of placebo-treated groups (MD [95% CI] of -9.20 [-14.11, -4.29], I(2)=34%). The pooled overall discontinuation rates between the two groups had no significant difference (RR [95% CI] of 0.82 [0.59, 1.14], I(2)=0%). Similarly, the pooled discontinuation rates due to adverse events between the two groups was not significantly different (RR [95% CI] of 1.77 [0.71, 4.40], I(2)=0%). CONCLUSION: The number of included studies was limited (five RCTs), but based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD. Additionally, it also improved the executive function deficits in this population. However, its acceptability is no higher than placebo. These findings should be carefully interpreted and considered as preliminary outcomes. To confirm these results, further studies are warranted. LDX is a viable alternative psychostimulant for adult ADHD.
AI snapshot
Written from the paper’s full text.
TL;DR
This exploratory meta-analysis of five randomized controlled trials found lisdexamfetamine (LDX) 30–70 mg/day was efficacious for adult ADHD and improved executive function compared with placebo, with acceptability and tolerability comparable to placebo. The authors caution that the small number of included trials and industry funding make the findings preliminary.
Key findings
- LDX significantly reduced ADHD symptom severity versus placebo: pooled mean change/end point SMD −0.97 (95% CI −1.15, −0.78), I²=18%; ADHD-RS-IV mean change SMD −0.85 (−1.07, −0.64), I²=0%; ADHD-RS-IV and CAARS end point SMD −1.14 (−1.41, −0.88), I²=0%.
- Response rates were significantly higher with LDX: RR 1.99 (95% CI 1.50, 2.63), I²=0%, with NNT 4 (95% CI 2.2, 4.5). Remission from one study also favored LDX: RR 2.82 (95% CI 1.58, 5.03).
- Executive function improved on BRIEF-A: Global Executive Composite MD −9.20 (95% CI −14.11, −4.29), I²=34%; BRI MD −6.52 (−12.45, −0.60), I²=56%; MI MD −10.38 (−14.47, −6.28), I²=0%.
- Overall discontinuation (RR 0.82, 95% CI 0.59, 1.14, I²=0%) and discontinuation due to adverse events (RR 1.77, 95% CI 0.71, 4.40, I²=0%) did not differ significantly from placebo.
Methods
- Systematic review and exploratory meta-analysis of randomized controlled trials comparing LDX with placebo in adult ADHD; databases searched in January 2014 included MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Controlled Trials Register, ClinicalTrials.gov, and EU Clinical Trials Register.
- Five RCTs were included, with 806 final study or safety participants; LDX dosage was 30–70 mg/day; study duration ranged from 4 to 14 weeks.
- Random-effects meta-analysis used relative risks for dichotomous outcomes and weighted mean differences or standardized mean differences with 95% CIs for continuous outcomes; heterogeneity assessed with I²; RevMan 5.1 used for synthesis.
Limitations
- Stated: only five RCTs were included, limiting meta-analytic power; all included trials were funded by the pharmaceutical company holding the LDX patent; pooled discontinuation rate alone was insufficient to determine safety, and other safety data such as adverse events, laboratory testing, and vital signs were not examined; statistical outlier and artifact analyses were not performed; publication bias was not assessed because fewer than ten studies were included.
- Evident from the text: several outcomes relied on very few studies—response rates from two studies, remission from one study, and discontinuation outcomes from four studies—so pooled estimates for those outcomes are especially fragile.
- Evident from the text: two included trials used crossover designs, and intention-to-treat analysis was applied in only two studies, which may affect comparability across trials.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
10 of 42 cited sources checked · 7 supported · 0 flagged · accuracy not yet measured
- Interpretationcitation
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”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [15] Madaan V Kolli V Bestha DP Shah MJ Update on optimal use of lisdexamfetamine in the treatment of ADHD Neuropsychiatr Dis Treat 2013 9 977 983 23901276 PMC3726586 source
- Interpretationcitation
The response rate of MPH ER versus placebo (50% vs 18%) and OROS MPH versus placebo (67% vs 37%) in adult ADHD is comparable with the response rate in this review (lisdexamfetamine 70% vs placebo 37%).
“Previous studies have shown that the response rate of MPH ER treatment vs placebo (50% vs 18%)31 and of OROS MPH treatment vs placebo (67% vs 37%)32 in adult ADHD is comparable with the response rate in this review (LDX [70%] vs placebo [37%]).”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [31] Retz W Rösler M Ose C Study Group Multiscale assessment of treatment efficacy in adults with ADHD: a randomized placebo-controlled, multi-centre study with extended-release methylphenidate World J Biol Psychiatry 2012 13 1 48 59 21155632 PMC3279134 source
- cites [32] Biederman J Mick E Surman C A randomized, 3-phase, 34-week, double-blind, long-term efficacy study of osmotic-release oral system-methylphenidate in adults with attention-deficit/hyperactivity disorder J Clin Psychopharmacol 2010 30 5 549 553 20814332 source
- Findingown data
Pooled discontinuation rates due to adverse events did not significantly differ between lisdexamfetamine and placebo in adult ADHD (RR 1.77, 95% CI 0.71 to 4.40, I2=0%).
“Similarly, the pooled discontinuation rates due to adverse events between the two groups was not significantly different (RR [95% CI] of 1.77 [0.71, 4.40], I2=0%).”
- Also stated in: § Synthesis of results · plain
“Additionally, the pooled discontinuation rates due to adverse events in this population between the two groups was not significantly different (RR (95% CI) of 1.77 [0.71, 4.40], I2=0%).”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Also stated in: § Synthesis of results · plain
- Findingown data
Pooled response rates for adult ADHD significantly differed between lisdexamfetamine and placebo (RR 1.99, 95% CI 1.50 to 2.63, I2=0%).
“The pooled response rates for adult ADHD between the two groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I2=0%).”
- Also stated in: § Synthesis of results · plain
“The pooled response rates for adult ADHD between LDX- and placebo-treated groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I2=0%) (Figure 3).”
- Also stated in: § Results of individual studies · plain
“Similarly, the response rate of adult ADHD was significantly different between the two groups (Figure 3).”
Quote in the paperSubstantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Also stated in: § Synthesis of results · plain
- Findingown data
Pooled overall discontinuation rates did not significantly differ between lisdexamfetamine and placebo in adult ADHD (RR 0.82, 95% CI 0.59 to 1.14, I2=0%).
“The pooled overall discontinuation rates between the two groups had no significant difference (RR [95% CI] of 0.82 [0.59, 1.14], I2=0%).”
- Also stated in: § Synthesis of results · plain
“The pooled overall discontinuation rates in adult ADHD between LDX- and placebo-treated groups did not show any significant differences (RR [95% CI] of 0.82 [0.59, 1.14], I2=0%).”
Quote in the paperSubstantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Also stated in: § Synthesis of results · plain
- Findingown data
Pooled mean change and end point scores on ADHD rating scales significantly differed between lisdexamfetamine and placebo in adult ADHD (SMD -0.97, 95% CI -1.15 to -0.78, I2=18%).
“The pooled mean scores of mean change and mean end point scores between LDX- and placebo-treated groups also had a significant difference (SMD [95% CI] of −0.97 [−1.15, −0.78], I2=18%).”
- Also stated in: § Synthesis of results · plain
“The pooled mean score of mean change and mean end point scores between two groups had also a significant difference (SMD [95% CI] of −0.97 [−1.15, −0.78], I2=18%) (Figure 2).”
Quote in the paperSubstantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Also stated in: § Synthesis of results · plain
- Findingown data
Pooled end point mean scores on the BRIEF-A Global Executive Composite were greater for lisdexamfetamine than for placebo in adult ADHD (MD -9.20, 95% CI -14.11 to -4.29, I2=34%).
“Based on the Behavior Rating Inventory of Executive Function – Adult version (BRIEF-A), the pooled end point mean scores for the Global Executive Composite (GEC) for the LDX-treated groups was greater than that of placebo-treated groups (MD [95% CI] of −9.20 [−14.11, −4.29], I2=34%).”
- Also stated in: § Synthesis of results · plain
“Finally, the pooled mean end point scores for the BRIEF-A Global Executive Composite for the LDX-treated groups was greater than that of placebo-treated groups, with MD (95% CI) of −9.20 (−14.11, −4.29), I2=34%.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Also stated in: § Synthesis of results · plain
- Findingown data
Five randomized controlled trials were included in this review.
“Then, five studies were included in this review.”
- Also stated in: § Discussion · plain
“This meta-analysis found five RCTs of LDX compared with placebo, in the treatment of adult ADHD.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Pooled mean end point scores of the Metacognition Index for lisdexamfetamine-treated groups were greater than for placebo-treated groups (MD -10.38, 95% CI -14.47 to -6.28, I2=0%).
“The pooled mean end point scores of the BRI and MI for the LDX-treated groups was greater than that of placebo-treated groups, with MD (95% CI) of −6.52 (−12.45, −0.60), I2=56, and MD (95% CI) of −10.38 (−14.47, −6.28), I2=0%, respectively.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Findingown data
The mean end point or mean change scores of the ADHD-RS-IV or CAARS short form in each study were significantly different between lisdexamfetamine- and placebo-treated groups.
“The mean end point or mean change scores of the ADHD Rating Scale version IV (ADHD-RS-IV) or Conners Adult ADHD Rating Scale (CAARS), short form in each study were significantly different between LDX- and placebo-treated groups (Figure 2).”
Quote in the paperSubstantial claim - Findingown data
Pooled mean end point scores of the Behavioral Regulation Index for lisdexamfetamine-treated groups were greater than for placebo-treated groups (MD -6.52, 95% CI -12.45 to -0.60, I2=56%).
“The pooled mean end point scores of the BRI and MI for the LDX-treated groups was greater than that of placebo-treated groups, with MD (95% CI) of −6.52 (−12.45, −0.60), I2=56, and MD (95% CI) of −10.38 (−14.47, −6.28), I2=0%, respectively.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Findingreasoning
The number needed to treat based on pooled response rates was 4 (95% CI 2.2 to 4.5).
“Based on its pooled response rates, the number need to treat (NNT) (95% CI) was 4 (2.2, 4.5).”
Quote in the paperSubstantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Findingown data
Pooled end point mean ADHD-RS-IV and CAARS scores significantly differed between lisdexamfetamine and placebo in adult ADHD (SMD -1.14, 95% CI -1.41 to -0.88, I2=0%).
“In addition, the pooled end point mean ADHD-RS-IV and CAARS scores between the two groups were also significantly different (SMD [95% CI] of −1.14 [−1.41, −0.88], I2=0%).”
Quote in the paperSubstantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Findingown data
Significant heterogeneity was not found in all efficacious outcomes except for the Behavioral Regulation Index.
“A significant heterogeneity was not found in all efficacious outcomes, except for the Behavioral Regulation Index (BRI).”
Quote in the paperNot a substantial claim - Findingown data
Pooled mean change ADHD-RS-IV scores significantly differed between lisdexamfetamine and placebo in adult ADHD (SMD -0.85, 95% CI -1.07 to -0.64, I2=0%).
“The pooled mean change ADHD-RS-IV scores of adult ADHD between LDX- and placebo-treated groups had a significant difference (SMD [95% CI] of −0.85 [−1.07, −0.64], I2=0%).”
Quote in the paperSubstantial claim- The authors state this as an assumption: The included studies do not share a single true effect size and are not exactly identical.
- Findingown data
The remission rate, from one study, showed a significant difference between lisdexamfetamine and placebo (RR 2.82, 95% CI 1.58 to 5.03).
“The remission rate, gathered from only one study, showed a significant difference between the two groups (RR [95% CI] of 2.82 [1.58, 5.03]).”
Quote in the paperNot a substantial claim - Findingown data
There were no relevant and unpublished trials that met the eligibility criteria.
“There were no relevant and unpublished trials that met the eligibility criteria.”
Quote in the paperNot a substantial claim - Interpretationown data
The tolerability of lisdexamfetamine, based on pooled rates of discontinuation due to adverse events, is comparable to placebo.
“In addition, its tolerability, based on the pooled rates of discontinuation due to adverse events, is also comparable.”
Quote in the paperSubstantial claim - Interpretationown data
The acceptability of lisdexamfetamine is no higher than placebo in adult ADHD.
“However, its acceptability is no higher than placebo.”
- Also stated in: § Discussion · plain
“According to this review, the acceptability of LDX treatment in adult ADHD was not higher than that of placebo, which is similar to the findings for other psychostimulants.”
- Also stated in: § Conclusion · plain
“However, its acceptability is no higher than that of placebo.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Interpretationcitation
The finding that lisdexamfetamine improves executive function in adult ADHD is similar to previous studies in adults with ADHD treated with psychostimulants such as MPH and nonstimulants such as atomoxetine.
“This finding is similar to previous studies in adults with ADHD treated with psychostimulants, such as MPH,35 and nonstimulants, such as atomoxetine.36”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [35] Fallu A Richard C Prinzo R Binder C Does OROS-methylphenidate improve core symptoms and deficits in executive function? Results of an open-label trial in adults with attention deficit hyperactivity disorder Curr Med Res Opin 2006 22 12 2557 2566 17166338 source
- cites [36] Brown TE Holdnack J Saylor K Effect of atomoxetine on executive function impairments in adults with ADHD J Atten Disord 2011 15 2 130 138 20026871 source
- Premisecitation
Persistent and remitted adult ADHD showed impairment of executive function based on a prospective study of ADHD in girls from childhood to young adulthood.
“Based on the prospective study of ADHD in girls from childhood to young adulthood, it was found that both persistent and remitted adult ADHD evidently showed impairment of executive function.”
Quote in the paperNot a substantial claim - Interpretationown data
The NNT of 4 suggests that one in every four adult patients with ADHD will benefit from lisdexamfetamine treatment.
“According to the pooled response rates, the NNT of 4 suggests that one in every four adult patients with ADHD will benefit from the LDX treatment.”
Quote in the paperSubstantial claim - Interpretationreasoning
Lisdexamfetamine is a viable alternative psychostimulant for adult ADHD.
“LDX is a viable alternative psychostimulant for adult ADHD.”
Quote in the paperSubstantial claim - Interpretationown data
Lisdexamfetamine improves executive function deficits in adult ADHD.
“Additionally, it also improved the executive function deficits in this population.”
- Also stated in: § Discussion · plain
“Additionally, this review also found that LDX improves executive function in those patients.”
- Also stated in: § Conclusion · plain
“Additionally, it also improves the executive function deficits in this population.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Premisecitation
Three in 5,422 people reported adverse events when taking lisdexamfetamine had cardiomyopathy (one male adult and two male teenagers).
“Recently, there was a report that three in 5,422 people reported adverse events when taking LDX had cardiomyopathy (one male adult and two male teenagers).38”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [38] ehealthme.com [homepage on the Internet] Could Vyvanse cause stress cardiomyopathy? eHealthMe 2014 [cited May 25, 2014]. Available from: http://www.ehealthme.com/ds/vyvanse/stresscardiomyopathy Accessed August 3, 2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Study design and conductnone given
Other safety data, such as adverse events, laboratory testing, and vital signs, were not examined in this review.
“Unfortunately, other safety data, for instance adverse events, laboratory testing, and vital signs, were not examined in this review; therefore, this agent should be used cautiously.”
Quote in the paperSubstantial claim - Study design and conductnone given
All included trials were funded by a pharmaceutical company holding the patent of lisdexamfetamine.
“Secondly, all included trials were funded by a pharmaceutical company holding the patent of LDX; hence, their outcomes should be carefully considered.”
Quote in the paperSubstantial claim - Study design and conductcitation
Publication bias was not assessed in this review due to the small number of included studies.
“Finally, as is well accepted, publication bias should be examined in meta-analysis but was not assessed here due to the small number of included studies.26”
- Also stated in: § Risk of bias across studies · plain
“In this review, only five trials were included, so it was difficult to distinguish the real chance asymmetry;26 therefore, the funnel plot was not carried out in this meta-analysis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Sterne JAC Egger M Moher D Addressing reporting biases Higgins JPT Green S Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 The Cochrane Collaboration 2009 [updated March 2011]. Available from: http://www.cochrane-handbook.org Accessed August 3, 2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § Risk of bias across studies · plain
- Premisecitation
The acceptability of MPH treatment in adult ADHD was not greater than that of placebo (OR 1.19, 95% CI 0.82 to 1.74).
“According to a recent meta-analysis, the acceptability of MPH treatment in adult ADHD was not greater than that of placebo (odds ratio [OR] 95% CI of 1.19 [0.82, 1.74]).37”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] Castells X Cunill R Capellà D Treatment discontinuation with methylphenidate in adults with attention deficit hyperactivity disorder: a meta-analysis of randomized clinical trials Eur J Clin Pharmacol 2013 69 3 347 356 22983311 source
- Premisecitation
The acceptability of OROS MPH in a recent review was worse than that of placebo.
“Unfortunately, the acceptability of OROS MPH in a recent review was worse than that of placebo.37”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] Castells X Cunill R Capellà D Treatment discontinuation with methylphenidate in adults with attention deficit hyperactivity disorder: a meta-analysis of randomized clinical trials Eur J Clin Pharmacol 2013 69 3 347 356 22983311 source
- Classified as probably not a substantial claim. 19
- May combine two claims. 12
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLisdexamfetamine 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”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [14] Elbe D Macbride A Reddy D Focus on lisdexamfetamine: A review of its use in child and adolescent psychiatry J Can Acad Child Adolesc Psychiatry 2010 19 4 303 314 21037922 PMC2962544
- cites [15] Madaan V Kolli V Bestha DP Shah MJ Update on optimal use of lisdexamfetamine in the treatment of ADHD Neuropsychiatr Dis Treat 2013 9 977 983 23901276 PMC3726586 source
May combine two claims.
PremisecitationSome randomized controlled trials of lisdexamfetamine demonstrated efficacy and tolerability compared with placebo in adult ADHD but had limited sample size.
“Although some randomized controlled trials (RCTs) of LDX demonstrated its efficacy and tolerability, compared with placebo, in the treatment of adult ADHD,16,18–21 they had a limited sample size.”
Quote in the paperSubstantial claim1 of 5 sources checked- cites [16] Adler LA Goodman DW Kollins SH 303 Study Group 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
- cites [18] Wigal T Brams M Gasior M Gao J Squires L Giblin J 316 Study Group 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 2010 6 34 20576091 PMC2908054 source
- cites [19] Biederman J Fried R Hammerness P The effects of lisdexamfetamine dimesylate on driving behaviors in young adults with ADHD assessed with the Manchester driving behavior questionnaire J Adolesc Health 2012 51 6 601 607 23174471 source
- cites [20] 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
- cites [21] Adler LA Dirks B Deas PF Lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study J Clin Psychiatry 2013 74 7 694 702 23945447 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAllocation concealment was reported in two trials.
“Additionally, allocation concealment was reported in two trials18,21 and blinding of outcome assessment was reported in three trials.16,20,21”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [18] Wigal T Brams M Gasior M Gao J Squires L Giblin J 316 Study Group 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 2010 6 34 20576091 PMC2908054 source
Methods > Study design (page not available) reports a fixed-block randomization schedule and a double-blind crossover phase, but does not describe whether treatment allocation was concealed before assignment. Searches for allocation concealment, concealed assignments, envelopes, and related procedures found no such report in our copy. This paper also cannot establish the citing sentence’s count of two trials. (LLM, conf=0.74)
Experimental — accuracy not yet measured - cites [21] Adler LA Dirks B Deas PF Lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study J Clin Psychiatry 2013 74 7 694 702 23945447 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSeveral stimulants are effective in the treatment of adult ADHD.
“Similar to present review, several stimulants are effective in the treatment of adult ADHD.”
Quote in the paperNot a substantial claim1 of 3 sources checked- cites [31] Retz W Rösler M Ose C Study Group Multiscale assessment of treatment efficacy in adults with ADHD: a randomized placebo-controlled, multi-centre study with extended-release methylphenidate World J Biol Psychiatry 2012 13 1 48 59 21155632 PMC3279134 source
- cites [32] Biederman J Mick E Surman C A randomized, 3-phase, 34-week, double-blind, long-term efficacy study of osmotic-release oral system-methylphenidate in adults with attention-deficit/hyperactivity disorder J Clin Psychopharmacol 2010 30 5 549 553 20814332 source
- cites [33] Casas M Rösler M Sandra Kooij JJ Efficacy and safety of prolonged-release OROS methylphenidate in adults with attention deficit/hyperactivity disorder: a 13-week, randomized, double-blind, placebo-controlled, fixed-dose study World J Biol Psychiatry 2013 14 4 268 281 22106853 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLisdexamfetamine 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”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [14] Elbe D Macbride A Reddy D Focus on lisdexamfetamine: A review of its use in child and adolescent psychiatry J Can Acad Child Adolesc Psychiatry 2010 19 4 303 314 21037922 PMC2962544
- cites [15] Madaan V Kolli V Bestha DP Shah MJ Update on optimal use of lisdexamfetamine in the treatment of ADHD Neuropsychiatr Dis Treat 2013 9 977 983 23901276 PMC3726586 source
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 measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLisdexamfetamine 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”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [14] Elbe D Macbride A Reddy D Focus on lisdexamfetamine: A review of its use in child and adolescent psychiatry J Can Acad Child Adolesc Psychiatry 2010 19 4 303 314 21037922 PMC2962544
- cites [15] Madaan V Kolli V Bestha DP Shah MJ Update on optimal use of lisdexamfetamine in the treatment of ADHD Neuropsychiatr Dis Treat 2013 9 977 983 23901276 PMC3726586 source
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 measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationTwo trials used double-blind, crossover study designs.
“Two trials used double-blind, crossover study designs.18,20”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [18] Wigal T Brams M Gasior M Gao J Squires L Giblin J 316 Study Group 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 2010 6 34 20576091 PMC2908054 source
- cites [20] 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
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationAn intention-to-treat analysis was applied in two studies.
“An intention-to-treat analysis was applied in two studies.16,18”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [16] Adler LA Goodman DW Kollins SH 303 Study Group 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
- cites [18] Wigal T Brams M Gasior M Gao J Squires L Giblin J 316 Study Group 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 2010 6 34 20576091 PMC2908054 source
May combine two claims.
FindingcitationMean end point or mean change scores were found in four studies, response rates in two studies, remission rate in one study, and overall discontinuation and discontinuation due to adverse events in four studies.
“Mean end point or mean change scores were found in four studies,16,18,20,21 response rates were reported in two studies,16,20 and remission rate was presented in one study.16 However, overall discontinuation rates and discontinuation due to adverse events were found in four studies.16,19–21”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataOnly one study reported remission rates, so pooled remission rate could not be calculated.
“Unfortunately, only one study reported remission rates,16 and its pooled remission rate could not be calculated.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Adler LA Goodman DW Kollins SH 303 Study Group 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
Classified as probably not a substantial claim.
Study design and conductreasoningThe funnel plot was not carried out in this meta-analysis because only five trials were included.
“In this review, only five trials were included, so it was difficult to distinguish the real chance asymmetry;26 therefore, the funnel plot was not carried out in this meta-analysis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Sterne JAC Egger M Moher D Addressing reporting biases Higgins JPT Green S Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 The Cochrane Collaboration 2009 [updated March 2011]. Available from: http://www.cochrane-handbook.org Accessed August 3, 2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAfter oral administration, lisdexamfetamine is converted to l-lysine and dextroamphetamine, which therapeutically affects ADHD symptoms.
“After oral administration, LDX, an originally inactive molecule, is rapidly absorbed from the gastrointestinal tract and converted to l-lysine, a naturally occurring essential amino acid, and dextroamphetamine, which therapeutically affects ADHD symptoms.13”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Blick SK Keating GM Lisdexamfetamine Paediatr Drugs 2007 9 2 129 135 discussion 136–138 17407369 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataExamination of risks of bias based on the Cochrane bias assessment was carried out in this review.
“Examination of risks of bias, based on the Cochrane bias assessment, was carried out.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationLisdexamfetamine is an effective, safe, well-tolerated medication for children aged 6 to 12 years through to adulthood with ADHD.
“The evidence suggests that LDX is an effective, safe, well-tolerated medication for children aged 6 to 12 years through to adulthood, with ADHD.16,17”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [16] Adler LA Goodman DW Kollins SH 303 Study Group 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
- cites [17] Faraone SV Lisdexamfetamine dimesylate: the first long-acting prodrug stimulant treatment for attention deficit/hyperactivity disorder Expert Opin Pharmacother 2008 9 9 1565 1574 18518785 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationA sequence generation of randomization was presented in one trial.
“A sequence generation of randomization was presented in one trial.21”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Adler LA Dirks B Deas PF Lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study J Clin Psychiatry 2013 74 7 694 702 23945447 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataAbstracts and full-text articles were examined independently by two authors, with disagreements resolved by consensus.
“To determine which studies conformed to the eligibility criteria, the abstracts, identified from the databases, were examined by the authors (NM and BM) independently. When attaining the full-text version of relevant articles, the authors then separately evaluated those studies. When disagreements took place, they were solved by consensus.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataBlinding of outcome assessment was reported in three trials.
“Additionally, allocation concealment was reported in two trials18,21 and blinding of outcome assessment was reported in three trials.16,20,21”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [16] Adler LA Goodman DW Kollins SH 303 Study Group 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
- cites [20] 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
- cites [21] Adler LA Dirks B Deas PF Lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study J Clin Psychiatry 2013 74 7 694 702 23945447 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataData extraction was performed by the first author and revised by the second reviewer, with disputes resolved by consensus.
“The first author (NM) extracted the relevant results into the data extraction form. Then, the second reviewer (BM) revised the extracted outcomes. All author disputes were also resolved by means of consensus.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationExecutive function deficit is related to academic underachievement in children with ADHD and with academic and occupational difficulties in adults with ADHD.
“Executive function deficit is related to academic underachievement in children with ADHD,34 and with both academic and occupational difficulties in adults with ADHD.5”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [34] Biederman J Monuteaux MC Doyle AE Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children J Consult Clin Psychol 2004 72 5 757 766 15482034 source
- cites [5] Biederman J Faraone SV Spencer TJ Mick E Monuteaux MC Aleardi M Functional impairments in adults with self-reports of diagnosed ADHD: A controlled study of 1001 adults in the community J Clin Psychiatry 2006 67 4 524 540 16669717 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPsychostimulants including methylphenidate, dextroamphetamine, and mixed amphetamine salts are efficacious in the treatment of ADHD in children, adolescents, and adults.
“Psychostimulants, including methylphenidate (MPH), dextroamphetamine, and mixed amphetamine salts are not only efficacious in the treatment of ADHD in children and adolescents but also, in adults.11,12”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [11] Castells X Ramos-Quiroga JA Rigau D Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis CNS Drugs 2011 25 2 157 169 21254791 source
- cites [12] Castells X Ramos-Quiroga JA Bosch R Nogueira M Casas M Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults Cochrane Database Syst Rev 2011 6 CD007813 21678370 source
May combine two claims.
Interpretationown dataLisdexamfetamine is efficacious and well tolerated in the treatment of adult ADHD.
“The number of included studies was limited (five RCTs), but based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD.”
- Also stated in: § Discussion · hedged
“This review suggests that LDX is effective in the treatment of adult ADHD.”
- Also stated in: § Conclusion · plain
“Based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD.”
Quote in the paperSubstantial claim- Also stated in: § Discussion · hedged
May combine two claims.
Study design and conductown dataRandomization and double-blind technique were applied in all eligible studies.
“The randomization, double-blind technique was applied in all eligible studies.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
InterpretationreasoningThe advantages of lisdexamfetamine may be explained by its prodrug formulation, which may reduce side effects observed in several other psychostimulants, and by the lisdexamfetamine metabolite dextroamphetamine, which is efficacious for ADHD treatment.
“These advantages of LDX may be explained by its prodrug formulation, which may reduce the side effects observed in several other psychostimulants, and by the LDX metabolite, dextroamphetamine, which is efficacious for ADHD treatment.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe number of included studies was limited (five RCTs), which may undermine the potential impact of meta-analysis.
“Firstly, the number of included studies was limited (five RCTs), which may undermine the potential impact of meta-analysis.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductreasoningPooled discontinuation rate alone was not sufficient to determine the safety of lisdexamfetamine.
“Thirdly, pooled discontinuation rate alone was not sufficient to determine the safety of LDX.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAnalysis of statistical outliers and artifacts study were not performed in this review.
“Fourthly, analysis of statistical outliers and artifacts study are useful in meta-analysis, unfortunately, they were not performed in this review.”
Quote in the paperNot a substantial claim
The authors state this as an assumption.
The included studies do not share a single true effect size and are not exactly identical.
“Although the eligible studies are a relative similarity, it is not able to assume that they are entirely same since one true effect size less plausibly exists. Hence, it is unlikely to assume that those studies are exactly identical.”
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.
Search period differs between the abstract and methods
MinorThe abstract says trials published from January 1991 were evaluated, while the methods say the related trials were searched from January 2007. The reported start date is inconsistent.
“Clinical trials published between January 1991 and January 2014 were evaluated.”
“The first publication of LDX in the MEDLINE® search was in 2007; therefore, the related clinical trials were searched between January 2007 and January 2014.”
Required outcomes were not reported by every included study
MinorThe eligibility criteria say response, remission, and discontinuation rates needed to be reported, but the results say remission was reported in only one of the five included studies, response in two, and discontinuation in four.
“In addition, response, remission, and discontinuation rates needed to be reported.”
“Mean end point or mean change scores were found in four studies,16,18,20,21 response rates were reported in two studies,16,20 and remission rate was presented in one study.16 However, overall discontinuation rates and discontinuation due to adverse events were found in four studies.16,19–21”
Cites
Assessing Risk of Bias in Included Studies
Higgins, J. P., & Altman, D. G. (2008) · Cochrane Handbook for Systematic Reviews of Interventions · doi:10.1002/9780470712184.ch8 · Cited by 3,396 · cited 1× · see citing works
“22”
Cipriani, A., Furukawa, T. A., Salanti, G., Geddes, J. R., Higgins, J. P., Churchill, R., Watanabe, N., Nakagawa, A., Omori, I. M., McGuire, H., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60046-5 · Cited by 1,654 · see citing works
Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis
Simon, V., Czobor, P., Bálint, S., Mészáros, Á., & Bitter, I. (2009) · British Journal of Psychiatry · doi:10.1192/bjp.bp.107.048827 · Cited by 1,601 · cited 1× · see citing works
“4%.(3,4) A previous study suggests that adult ADHD is associated with greater impairment in various areas of functioning.”
Biederman, J., Monuteaux, M. C., Doyle, A. E., Seidman, L. J., Wilens, T. E., Ferrero, F., Morgan, C. L., & Faraone, S. V. (2004) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.72.5.757 · Cited by 881 · cited 4× · see citing works
“Keywords: lisdexamfetamine, placebo, systematic review, adult ADHD, acceptability, tolerability”
InfluentialWEISS, G., HECHTMAN, L., MILROY, T., & PERLMAN, T. (1985) · Journal of the American Academy of Child Psychiatry · doi:10.1016/s0002-7138(09)60450-7 · Cited by 753 · cited 1× · see citing works
“Background Although its symptoms initially occur in early childhood and usually decline in adulthood, a symptom of inattention persisting through into adulthood is still common.(1,2) Recent evidence suggests that adult attention-deficit hyperactivity disorder (ADHD) prevalence ranges from 2.”
Barkley, R. A., Grodzinsky, G., & DuPaul, G. J. (1992) · Journal of Abnormal Child Psychology · doi:10.1007/bf00916547 · Cited by 724 · cited 1× · see citing works
“In addition to its inattention symptoms, frequently ADHD affects executive function.(6,7) Therefore, adult ADHD patients may encounter several difficulties, including on-task behavior, academic achievement, and social functioning(8,9) Recent evidence suggests that onset of ADHD in childhood may be associated with work…”
Sterne, J. A., Egger, M., & Moher, D. (2008) · Cochrane Handbook for Systematic Reviews of Interventions · doi:10.1002/9780470712184.ch10 · Cited by 651 · cited 2× · see citing works
“( P =0. difficult to distinguish the real chance asymmetry; 26 therefore, the funnel plot was not carried out in this meta-analysis.”
Biederman, J., Faraone, S. V., Spencer, T. J., Mick, E., Monuteaux, M. C., & Aleardi, M. (2006) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v67n0403 · Cited by 565 · cited 13× · see citing works
“A previous study suggests that adult ADHD is associated with greater impairment in various areas of functioning.(5) In addition to its inattention symptoms, frequently ADHD affects executive function.”
InfluentialEpidemiology of attention-deficit/hyperactivity disorder across the lifespan
Polanczyk, G. V., & Rohde, L. A. (2007) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e3281568d7a · Cited by 483 · cited 1× · see citing works
“4%.(3,4) A previous study suggests that adult ADHD is associated with greater impairment in various areas of functioning.”
Wiebe, N., Vandermeer, B., Platt, R. W., Klassen, T. P., Moher, D., & Barrowman, N. J. (2006) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2005.08.017 · Cited by 296 · 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 2× · see citing works
“Adler et al 2008 16 Dupaul et al 2012 20 bias should be examined in meta-analysis but was not assessed here due to the small number of included studies.”
Clark, C., Prior, M., & Kinsella, G. J. (2000) · Journal of Abnormal Child Psychology · doi:10.1023/a:1005176320912 · Cited by 211 · cited 1× · see citing works
“In addition to its inattention symptoms, frequently ADHD affects executive function.(6,7) Therefore, adult ADHD patients may encounter several difficulties, including on-task behavior, academic achievement, and social functioning(8,9) Recent evidence suggests that onset of ADHD in childhood may be associated with work…”
Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults
Castells, X., Blanco-Silvente, L., & Cunill, R. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007813.pub3 · Cited by 209 · see citing works
Castells, X., Ramos-Quiroga, J. A., Rigau, D., Bosch, R., Nogueira, M., Vidal, X., & Casas, M. (2011) · CNS Drugs · doi:10.2165/11539440-000000000-00000 · Cited by 197 · cited 1× · see citing works
“11,12 The novel psychostimulant, lisdexamfetamine (LDX), is also efficacious in the treatment of ADHD.”
Literature Review: ADHD in Adults
Davidson, M. A. (2007) · Journal of Attention Disorders · doi:10.1177/1087054707310878 · Cited by 190 · cited 1× · see citing works
“Background Although its symptoms initially occur in early childhood and usually decline in adulthood, a symptom of inattention persisting through into adulthood is still common.(1,2) Recent evidence suggests that adult attention-deficit hyperactivity disorder (ADHD) prevalence ranges from 2.”
Management of Patients With Treatment-Resistant Depression
Thase, M. E. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.0308e08 · Cited by 158 · see citing works
Wigal, 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 · cited 7× · see citing works
“18,20 An intention-to-treat analysis was applied in two studies.”
InfluentialDuPaul, 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 · cited 7× · see citing works
“18,20 An intention-to-treat analysis was applied in two studies.”
InfluentialGreenhill, L. L., Pliszka, S. R., Dulcan, M. K., Bernet, W., Arnold, V., Beitchman, J. H., Benson, R. S., Bukstein, O. G., Kinlan, J., McClellan, J., et al. (2001) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200111000-00020 · Cited by 85 · cited 1× · see citing works
“6,7 Therefore, adult ADHD patients may encounter several difficulties, including on-task behavior, academic achievement, and social functioning 8,9 Recent evidence suggests that onset of ADHD in childhood may be associated with working disabilities in adults.”
Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults
Castells, X., Ramos-Quiroga, J. A., Bosch, R., Nogueira, M., & Casas, M. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007813.pub2 · Cited by 80 · cited 1× · see citing works
“Psychostimulants, including methylphenidate (MPH), dextroamphetamine, and mixed amphetamine salts are not only efficacious in the treatment of ADHD in children and adolescents but also, in adults.(11,12) The novel psychostimulant, lisdexamfetamine (LDX), is also efficacious in the treatment of ADHD.”
Retz, W., Rösler, M., Ose, C., Scherag, A., Alm, B., Philipsen, A., Fischer, R., Ammer, R., & The Study Group (2012) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2010.540257 · Cited by 79 · cited 6× · see citing works
“According to a recent meta-analysis, the acceptability of MPH treatment in adult ADHD was not greater than that of placebo (odds ratio [OR] 95% CI of 1.19 [0.82, 1.74]).”
InfluentialBiederman, J., Mick, E., Surman, C., Doyle, R., Hammerness, P., Kotarski, M., & Spencer, T. (2010) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181ee84a7 · Cited by 76 · cited 2× · see citing works
“32 in adult ADHD is comparable with the response rate in this review (LDX [70”
Adler, L. A., Dirks, B., Deas, P. F., Raychaudhuri, A., Dauphin, M. R., Lasser, R. A., & Weisler, R. H. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.12m08144 · Cited by 62 · cited 6× · see citing works
“The summation of the BRI and MI provides an overall index, called the Global Executive Composite.(20,21) The pooled mean end point scores of the BRI and MI for the LDX-treated groups was greater than that of placebo-treated groups, with MD (95% CI) of -6.”
InfluentialEffect of Atomoxetine on Executive Function Impairments in Adults With ADHD
Brown, T. E., Holdnack, J., Saylor, K., Adler, L., Spencer, T., Williams, D. W., Padival, A. K., Schuh, K., Trzepacz, P. T., & Kelsey, D. (2011) · Journal of Attention Disorders · doi:10.1177/1087054709356165 · Cited by 59 · cited 1× · see citing works
“This finding is similar to previous studies in adults with ADHD treated with psychostimulants, such as MPH,(35) and nonstimulants, such as atomoxetine.(36) According to this review, the acceptability of LDX treatment in adult ADHD was not higher than that of placebo, which is similar to the findings for other psychost…”
Blick, S. K. A., & Keating, G. M. (2007) · Pediatric Drugs · doi:10.2165/00148581-200709020-00007 · Cited by 50 · see citing works
Surman, C. B. H., & Roth, T. (2011) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11m06838 · Cited by 42 · see citing works
Fallu, A., Richard, C., Prinzo, R., & Binder, C. (2006) · Current Medical Research and Opinion · doi:10.1185/030079906x154132 · Cited by 42 · cited 1× · see citing works
“This finding is similar to previous studies in adults with ADHD treated with psychostimulants, such as MPH, 35 and nonstimu-lants, such as atomoxetine.”
Brams, 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 · cited 1× · see citing works
“Five more articles were excluded, since three were the post hoc analysis using data from previous studies, 27–29 one had a randomized withdrawal study design, 30 not report the outcomes of interest applied for this analysis.”
Castells, X., Cunill, R., & Capellà, D. (2013) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-012-1390-7 · Cited by 41 · cited 2× · see citing works
“Unfortunately, the acceptability of OROS MPH in a recent review was worse than that of placebo.(37) These advantages of LDX may be explained by its prodrug formulation, which may reduce the side effects observed in several other psychostimulants, and by the LDX metabolite, dextroamphetamine, which is efficacious for A…”
Casas, M., Rösler, M., Sandra Kooij, J. J., Ginsberg, Y., Ramos-Quiroga, J. A., Heger, S., Berwaerts, J., Dejonckheere, J., van der Vorst, E., & Schäuble, B. (2013) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.600333 · Cited by 38 · cited 1× · see citing works
“For instance, recent evidence has shown the efficacy of the extended-release (ER) formulation of MPH 31 and osmotic-release oral system (OROS) MPH. 32,33 Previous studies have shown that the response rate of MPH ER treatment vs placebo (50% vs 18”
Faraone, S. V. (2008) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.9.9.1565 · Cited by 33 · cited 12× · see citing works
“Executive function deficit is related to academic underachievement in children with ADHD, 34 and with both academic and occupational difficulties in adults with ADHD.”
InfluentialMattingly, G. W., Weisler, R. H., Young, J. L., Adeyi, B. A., Dirks, B., Babcock, T., Lasser, R. A., Scheckner, B., & Goodman, D. W. (2013) · BMC Psychiatry · doi:10.1186/1471-244x-13-39 · Cited by 32 · cited 1× · see citing works
“Five more articles were excluded, since three were the post hoc analysis using data from previous studies, 27–29 one had a randomized withdrawal study design, 30 not report the outcomes of interest applied for this analysis.”
Mørdre, M., Grøholt, B., Sandstad, B., & Myhre, A. M. (2012) · BMC Psychiatry · doi:10.1186/1471-244x-12-174 · Cited by 31 · cited 1× · see citing works
“Therefore, adult ADHD patients may encounter several difficulties, including on-task behavior, academic achievement, and social functioning(8,9) Recent evidence suggests that onset of ADHD in childhood may be associated with working disabilities in adults.(10) Psychostimulants, including methylphenidate (MPH), dextroa…”
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 Adolescent Health · doi:10.1016/j.jadohealth.2012.03.005 · Cited by 24 · see citing works
Update on optimal use of lisdexamfetamine in the treatment of ADHD
Madaan, V., Kolli, V., Bestha, D., & Shah, M. (2013) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s34092 · Cited by 19 · cited 2× · 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…”
Focus on Lisdexamfetamine: A Review of its use in Child and Adolescent Psychiatry.
(2010) · Europe PMC (PubMed Central) · Cited by 10 · see citing works
Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults With ADHD
Faraone, S. V., Spencer, T. J., Kollins, S. H., Glatt, S. J., & Goodman, D. (2011) · Journal of Attention Disorders · doi:10.1177/1087054711403716 · Cited by 9 · cited 1× · see citing works
“not report the outcomes of interest applied for this analysis.(9) Then, five studies were included in this review.”
Update on optimal use of lisdexamfetamine in the treatment of ADHD
Madaan, V., Kolli, V. B., Bestha, D. P., et al. (2013) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [24]Papakostas GI Tolerability of modern antidepressants J Clin Psychiatry 2008 69 Suppl E1 8 13 18494538
Cited by
Sorted by citations
Updated European Consensus Statement on diagnosis and treatment of adult ADHD
Kooij, J. J. S., Bijlenga, D., Salerno, L., Jaeschke, R., Bitter, I., Balázs, J., Thome, J., Dom, G., Kasper, S., Nunes Filipe, C., et al. (2019) · European Psychiatry · doi:10.1016/j.eurpsy.2018.11.001 · Cited by 686 · see citing works
Leichsenring, F., Steinert, C., Rabung, S., & Ioannidis, J. P. A. (2022) · World Psychiatry · doi:10.1002/wps.20941 · Cited by 485 · see citing works
Pharmacological and non-pharmacological treatment of adults with ADHD: A meta-review
De Crescenzo, F., Cortese, S., Adamo, N., & Janiri, L. (2017) · Evidence Based Mental Health · doi:10.1136/eb-2016-102415 · Cited by 150 · see citing works
“78).(20) Atomoxetine, a non-psychostimulant pharmacological treatment, was found to be more efficacious than placebo in reducing ADHD symptom severity, according to clinician (SMD 0.”
BackgroundNew onset executive function difficulties at menopause: a possible role for lisdexamfetamine
Epperson, C. N., Shanmugan, S., Kim, D. R., Mathews, S., Czarkowski, K. A., Bradley, J., Appleby, D. H., Iannelli, C., Sammel, M. D., & Brown, T. E. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3953-7 · Cited by 90 · see citing works
“Although the tolerability and safety profile of short-term LDX treatment was observed in this study, long-term studies of menopausal women receiving LDX would be required to confirm a positive risk–benefit profile like that observed for the drug among adults with ADHD (Maneeton et al. 2014).”
Cunill, R., Castells, X., Tobías, A., & Capellà, D. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4099-3 · Cited by 77 · see citing works
“cious than placebo for reducing ADHD symptoms (Asherson et al. 2014; Epstein et al. 2014; Maneeton et al. 2011; Maneeton et al. 2014); thus, pharmacological manage-”
BackgroundA systematic meta-review of systematic reviews on attention deficit hyperactivity disorder
Chaulagain, A., Lyhmann, I., Halmøy, A., Widding‐Havneraas, T., Nyttingnes, O., Bjelland, I., & Mykletun, A. (2023) · European Psychiatry · doi:10.1192/j.eurpsy.2023.2451 · Cited by 93 · see citing works
Neurocognitive, Autonomic, and Mood Effects of Adderall: A Pilot Study of Healthy College Students
Weyandt, L. L., White, T. L., Gudmundsdottir, B. G., Nitenson, A. Z., Rathkey, E. S., De Leon, K. A., & Bjorn, S. A. (2018) · Pharmacy · doi:10.3390/pharmacy6030058 · Cited by 43 · see citing works
Stuhec, M., Lukić, P., & Locatelli, I. (2019) · Annals of Pharmacotherapy · doi:10.1177/1060028018795703 · Cited by 46 · see citing works
“78).(18) This meta-analysis includes new studies with LDX for treatment of ADHD in adults.”
BackgroundMethodHutchison, S. L., GHUMAN, J. K., Ghuman, H. S., Karpov, I. O., & Schuster, J. M. (2016) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125316647686 · Cited by 41 · 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
“14]).(42) In addition, a systematic review also showed that acceptability of MPH and atomoxetine treatments in child and adolescent ADHD was comparable.”
Self-citationManeeton, N., Woottiluk, P., Suttajit, S., Likhitsathian, S., Charnsil, C., Srisurapanont, M., & Maneeton, B. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s91765 · Cited by 12 · see citing works
“40,41 Based on the discontinuous rate due to adverse events, the tolerability of d-MPH was comparable to that of the placebo.”
Self-citationDevelopment of the Korean Practice Parameter for Adult Attention-Deficit/Hyperactivity Disorder
Bahn, G. H., Lee, Y. S., Yoo, H. K., Kim, E., Park, S., Han, D. H., Hong, M., Kim, B., Lee, S. I., Bhang, S., et al. (2019) · Journal of korean Academy of Child and Adolescent Psychiatry · doi:10.5765/jkacap.190030 · Cited by 14 · 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
Aufmerksamkeitsdefizit‑/Hyperaktivitätsstörung im Kindes- und Jugendalter
Häge, A., Hohmann, S., Millenet, S., & Banaschewski, T. (2020) · Der Nervenarzt · doi:10.1007/s00115-020-00904-1 · Cited by 9 · see citing works
Alda, J. A., Cardo, M. E., del Campo, P. D., García, A., Gurrea, A., & Izaguirre, J. (2017) · GuíaSalud eBooks · doi:10.46995/gpc_574 · Cited by 9 · see citing works
Tajik, A. J., Nikfar, S., Elyasi, S., Rajabi, O., & Varmaghani, M. (2023) · Child and Adolescent Psychiatry and Mental Health · doi:10.1186/s13034-023-00664-1 · Cited by 8 · see citing works
Gonda, X., Döme, P., Balogh, L., Baradits, M., & Réthelyi, J. (2026) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2026.108997 · Cited by 3 · see citing works
da Silva, J. V. H., Erthal, R. P., Vercellone, I. C., dos Santos, D. P., Ferraz, C. R., de Matos, R. L. N., Gonçalves, L. E. D., Bracarense, A. P. F. R. L., Verri, W. A., Jr., Câmara, N. O. S., et al. (2024) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23781 · Cited by 2 · see citing works
Fricke, U., Hein, L., & Schwabe, U. (2020) · Springer eBooks · doi:10.1007/978-3-662-62168-4_2 · Cited by 2 · see citing works
Kooij, J. J. S. (2021) · Springer eBooks · doi:10.1007/978-3-030-82812-7_4 · Cited by 2 · see citing works
Review of Clinical Considerations in the Management of Adolescents with ADHD During Ramadan
Khan, F., & Mohiuddin, S. S. (2024) · Adolescent Psychiatry · doi:10.2174/0122106766298494240510052101 · Cited by 1 · see citing works
Ellwanger, M. P., Pomianoski, B. W., Vieira, D. L., Ellwanger, M. P., Astori, V., & Messinger, M. F. (2025) · European Eating Disorders Review · doi:10.1002/erv.70070 · Cited by 2 · see citing works
ADHD and Co-Occurring Substance Use Disorders
Hernández, M., Dambreville, N., & LEVIN, F. R. (2022) · Springer eBooks · doi:10.1007/978-3-030-84834-7_2 · Cited by 1 · see citing works
Efficacy of Amphetamines, Methylphenidate, and Modafinil in the Treatment of Mental Disorders
Retz, W. (2022) · Springer eBooks · doi:10.1007/978-3-030-62059-2_319 · Cited by 1 · see citing works
Kritische Entwicklungsaufgaben und ihre Bewältigung
Ströhlein, B., Groß, V., & Philipsen, A. (2016) · NeuroTransmitter · doi:10.1007/s15016-016-5751-9
Efficacy of Amphetamines, Methylphenidate, and Modafinil in the Treatment of Mental Disorders
Retz, W. (2021) · Springer eBooks · doi:10.1007/978-3-319-56015-1_319-1
PHARMACOLOGICAL TREATMENT STRATEGIES FOR ADHD: A SYSTEMATIC REVIEW
Grzesikowski, P., Klich, P., Bekier, K., Kubiak, J., Górski, J., Nowicka, H., Liszka, D., Joks, M. M., Ordon, E., & Ostromecka, K. (2025) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(47).2025.3814 · Cited by 1 · see citing works
- Authors
- Maneeton, B., Maneeton, N., Suttajit, S., Reungyos, J., Srisurapanont, M., & Martin, S.
- Affiliations
- Chiang Mai University (TH)
- Venue
- Drug Design, Development and Therapy
- Publisher
- Informa UK Limited
- Published
- 2014-10
- Volume
- 8
- Pages
- 1685
- ISSN
- 1177-8881 (ISSN-L)
- PMC
- PMC4199984
- OpenAlex
- W2081678288
- Cited by
- 27
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 4
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Design Development and Therapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- Chiang Mai University
- Faculty of Medicine, Chiang Mai University
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- lisdexamfetamine, adult ADHD, stimulant medication, ADHD symptom severity, executive function, treatment response rate, remission rate, treatment discontinuation, adverse events, tolerability, acceptability, placebo comparison, BRIEF-A, Behavior Rating Inventory of Executive Function, ADHD Rating Scale, risk of bias, treatment effect heterogeneity, dose-response relationship
- MeSH terms
- Lisdexamfetamine Dimesylate, Attention Deficit Disorder with Hyperactivity, Dextroamphetamine, Humans, Placebos, Registries, Databases, Factual
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-16.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-16.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
