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

May combine two claims.

In that 12-week trial, AMSES and AMRS had high internal consistency and demonstrated that LDX had a smooth and consistent effect throughout the day at lower and higher doses, with no reported worsening of symptoms in the evening, suggesting no symptom rebound with LDX.

“Both the AMSES and AMRS had high internal consistency and demonstrated that LDX had a smooth and consistent effect throughout the day at lower and higher doses, with no reported worsening of symptoms in the evening, suggesting no symptom rebound with LDX.”

• cites [25] Adler LA Lynch LR Shaw DM Effectiveness and duration of effect of open-label lisdexamfetamine dimesylate in adults with ADHD. J Atten Disord. 2017; 21: 149– 157. 23657761 sourceDisputed

  Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

In that 12-week trial, secondary outcome measures of ASRS v1.1 Symptom Checklist significantly improved from baseline to study end point (42% reduction), as well as total scores of TASS, with reductions in 47% in-clinic and 53% evening.

“Secondary outcome measures of ADHD Self-Report Scale (ASRS) v1.1 Symptom Checklist significantly improved from baseline to study end point (42% reduction), as well as total scores of Time-Sensitive ADHD Symptom Scales (TASS), with reductions in 47% (in-clinic) and 53% (evening) (all P’s < .001).”

• cites [25] Adler LA Lynch LR Shaw DM Effectiveness and duration of effect of open-label lisdexamfetamine dimesylate in adults with ADHD. J Atten Disord. 2017; 21: 149– 157. 23657761 sourceDisputed

  The Methods describe a seven-day-per-treatment crossover study whose secondary ADHD symptom measure was CAARS-S:S, not ASRS or TASS. The Discussion explicitly says that this secondary efficacy outcome did not improve versus placebo. The claimed 12-week duration and 42%, 47%, and 53% reductions are not reported in our copy. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

In a 12-week randomized open-label trial by Adler et al, from baseline to end of study period there was a 47% reduction in mean total ADHD-RS score, with significant improvement in inattentive and hyperactive/impulsive subscale scores.

“From baseline to end of study period, there was a 47% reduction in the mean total ADHD-RS score (P < .001), with significant improvement in inattentive and hyperactive/impulsive subscale scores (P < .005).”

• cites [25] Adler LA Lynch LR Shaw DM Effectiveness and duration of effect of open-label lisdexamfetamine dimesylate in adults with ADHD. J Atten Disord. 2017; 21: 149– 157. 23657761 sourceDisputed

  The Methods describe a double-blind, placebo-controlled crossover study with three 7-day treatment periods, not a 12-week open-label trial. The Results report only a baseline ADHD-RS-IV score, while the Discussion says the measured CAARS-S:S symptom scores did not differ between active treatment and placebo. Our copy does not report a 47% reduction or the claimed subscale improvements. (LLM, conf=0.86)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Long-acting preparations may minimize the daily peaks and troughs of therapeutic effects associated with shorter acting agents and may minimize the potential for rebound symptoms later in the day.

“long-acting preparations may minimize the daily peaks and troughs of therapeutic effects associated with the shorter acting agents and also minimize the potential for rebound symptoms later in the day”

• cites [9] Brams M Moon E Pucci M López FA. Duration of effect of oral long-acting stimulant medications for ADHD throughout the day. Curr Med Res Opin. 2010; 26: 1809– 1825. 20491612 sourceNot checked — no full text of the source
• cites [10] López FA Leroux JR. Long-acting stimulants for treatment of attention-deficit/hyperactivity disorder: a focus on extended-release formulations and the prodrug lisdexamfetamine dimesylate to address continuing clinical challenges. Atten Defic Hyperact Disord. 2013; 5: 249– 265. 23564273 PMC3751218 sourcePartly supported

  The Introduction (page unavailable) says short-acting stimulants can leave fragmented coverage and that long-acting formulations were developed to relieve symptoms throughout the day without repeat dosing. This supports the claim about reducing fluctuations in therapeutic coverage, but our copy does not say that long-acting preparations minimize later-day rebound symptoms. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

LDX is approved for binge eating disorder in adults in the United States.

“In addition, it is approved for binge eating disorder in adults in the United States.”

• cites [14] Vyvanse (lisdexamfetamine dimesylate) [package insert]. Lexington, MA: Shire US, Inc.; 1 2017 http://pi.shirecontent.com/PI/PDFs/Vyvanse_USA_ENG.pdf. sourceCould not verify

  The Introduction describes LDX as indicated for ADHD in children, adolescents, and adults; it does not address approval for binge eating disorder in US adults. Searches for binge eating disorder and FDA approval found no passage addressing that claim. The ADHD indication does not, by itself, contradict a separate indication. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

LDX is approved for ADHD use in children, adolescents, and adults in the United States, Canada, Denmark, Finland, Germany, Ireland, Norway, Spain, Sweden, and the United Kingdom, and in children in Brazil.

“Lisdexamfetamine dimesylate is approved for ADHD use in children, adolescents, and adults in the United States (Vyvanse), Canada (Vyvanse), Denmark (Elvanse), Finland (Elvanse) Germany (Elvanse), Ireland (Tyvense), Norway (Elvanse), Spain (Elvanse), Sweden (Elvanse), and United Kingdom (Elvanse) and in children in Brazil (Venvanse).”

• cites [11] Najib J. Lisdexamfetamine in the treatment of adolescents and children with attention-deficit/hyperactivity disorder. Adolesc Health Med Ther. 2012; 3: 51– 66. 24600287 PMC3915893 sourcePartly supported

  The ADHD management section says LDX was approved for children in 2007 and adolescents in 2010; the Adolescents section specifies FDA approval for adolescents in the United States. The paper does not establish approval for adults or the claimed approvals in Canada, the listed European countries, or Brazil, nor does it provide the brand names. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [12] Frampton JE. Lisdexamfetamine: a review in ADHD in adults. CNS Drugs. 2016; 10: 1007– 1012. 27048350 sourceNot checked — no full text of the source
• cites [13] Alda JA Soutullo C Ramos-Quiroga JA Expert recommendation: contributions to clinical practice of the new prodrug lisdexamfetamine dimesylate (LDX) in the treatment of attention deficit hyperactivity disorder (ADHD). Actas Esp Psiquiatr. 2014; 42: 1– 16. 25644658Not checked — no full text of the source

May combine two claims.

In the 10-week Adler et al trial, significantly more patients treated with LDX were rated as improved on CGI-I beginning at week 1 through week 9, and at week 10, 79% of LDX-treated participants were rated as improved compared with 34.7% of placebo patients.

“Significantly, more patients treated with LDX rated as improved on the CGI-I (P ≤ .0125) beginning at week 1 through week 9, and at week 10, 79% of LDX-treated participants were rated as improved, compared with 34.7% of patients receiving placebo (P < .0001).”

• cites [23] 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: 694– 702. 23945447 sourcePartly supported

  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

May combine two claims.

LDX is not metabolized by cytochrome P450 enzymes and is unlikely to be involved in drug interactions involving CYP enzymes or P-glycoprotein; however, it is contraindicated during or within 2 weeks following administration of monoamine oxidase inhibitors.

“Lisdexamfetamine dimesylate is not metabolized by cytochrome P450 enzymes and unlikely to be involved in drug interactions involving CYP enzymes or P-glycoprotein; however, it is contraindicated during or within 2 weeks following the administration of monoamine oxidase inhibitors.”

• cites [16] Hutson PH Pennick M Secker R. Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug. Neuropharmacology. 2014; 87: 41– 50. 24594478 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [21] Najib J. The efficacy and safety profile of lisdexamfetamine dimesylate, a prodrug of d-amphetamine, for the treatment of attention-deficit/hyperactivity disorder in children and adults. Clin Ther. 2009; 31: 142– 176. 19243715 sourceNot checked — no full text of the source

May combine two claims.

In the 10-week Adler et al trial, at week 10, LDX compared with placebo was associated with significantly greater improvements in ADHD-RS-IV total scores, greater reductions from baseline in mean BRIEF-A GEC T scores, and significantly greater improvements in all 9 clinical subscales.

“At week 10, LDX compared with placebo was associated with significantly greater improvements in ADHD-RS-IV total scores (P < .0001), with greater reductions from baseline in mean BRIEF-A GEC T scores (P < .0001), and with significantly greater improvements in all the measure’s 9 clinical subscales from baseline (P ≤ .0056).”

• cites [23] 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: 694– 702. 23945447 sourcePartly supported

  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

May combine two claims.

In another post hoc analysis of the AWE study, mean BADDS total score decreased from 74.3 at baseline to 40.9 at dose-optimization week 4 for all LDX doses (P < .0001), and optimal response was observed in 67% based on BADDS at week 4.

“Likewise, another post hoc analysis of the AWE study noted the mean BADDS total score from baseline to dose-optimization week 4 decreased from 74.3 to 40.9 for all LDX doses (P < .0001), and the optimal response was observed in 67% of the patients based on BADDS scores at week 4.”

• cites [42] Brown TE Brams M Gasior M Clinical utility of ADHD symptom thresholds to assess normalization of executive function with lisdexamfetamine dimesylate treatment in adults. Curr Med Res Opin. 2011; 27: 23– 33. 21973229 sourceCould not verify

  The Methods describe a three-week LDX trial in eight parents of adolescents, with ADHD-RS and CGI assessments; the Results report observed parent–adolescent interactions. Searches for BADDS scores and the AWE week-4 analysis found no passage reporting the claimed scores, P value, or 67% response rate. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

In phase 2 of Waxmonsky et al, there was a statistically significant increase in praise by parents, and reductions in parental commands, and in children's inappropriate behaviors (P < .05 for all).

“In phase 2, there was a statically significant increase in praise by parents, and reductions in parental commands, and in children’s inappropriate behaviors (P < .05, for all).”

• cites [35] Waxmonsky JG Waschbusch DA Babinski DE Does pharmacological treatment of ADHD in adults enhance parenting performance? results of a double-blind randomized trial. CNS Drugs. 2014; 28: 665– 677. 24796970 sourceCould not verify

  The Results (Primary efficacy measures; Other efficacy measures, pages unavailable) report ADHD symptom outcomes in adults treated with lisdexamfetamine, not a phase 2 study of parent–child behavior. Searches for Waxmonsky, parental praise and commands, and children’s inappropriate behavior found no passage reporting the claimed changes or P values. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

In Waxmonsky et al, reductions in parental verbalizations, moderate increases in parental responsiveness, and reductions in ratio of commands to verbalizations during the non-homework task were not significant.

“Although not significant, there were also reductions in parental verbalizations, moderate increases in parental responsiveness, and reductions in the ratio of commands to verbalizations during the non-homework task.”

• cites [35] Waxmonsky JG Waschbusch DA Babinski DE Does pharmacological treatment of ADHD in adults enhance parenting performance? results of a double-blind randomized trial. CNS Drugs. 2014; 28: 665– 677. 24796970 sourceCould not verify

  The Results (Other efficacy measures; page unavailable) report ADHD response and remission in adults treated with lisdexamfetamine, not parent–child interactions. Searches for parental verbalizations, responsiveness, command ratios, non-homework tasks, and Waxmonsky found no passage addressing the claim. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

In phase 1 of Waxmonsky et al, there were significant reductions in negative talk by parents (P = .0066) and in children's negative behaviors in the homework phase only (P = .0154).

“In phase 1, there were significant reductions in negative talk by parents (P = .0066) and in children’s negative behaviors in the homework phase only (P = .0154).”

• cites [35] Waxmonsky JG Waschbusch DA Babinski DE Does pharmacological treatment of ADHD in adults enhance parenting performance? results of a double-blind randomized trial. CNS Drugs. 2014; 28: 665– 677. 24796970 sourceCould not verify

  The Results (Primary efficacy measures and Other efficacy measures; page unavailable) report ADHD symptom scores and clinical response in adults treated with lisdexamfetamine. Searches for Waxmonsky, parental negative talk, children’s behavior during homework, and the stated P values found no passage addressing the claim. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

In Waxmonsky et al, LDX was associated with significant reductions in children's negative behaviors and improvements in multiple parenting behaviors adversely affected by ADHD, and significant reductions in parental ADHD symptoms compared with placebo (P < .005).

“In addition to use of LDX being associated with significant reductions in children’s negative behaviors and improvements in multiple parenting behaviors adversely affected by ADHD, significant reductions in parental ADHD symptoms compared with placebo were also observed (P < .005).”

• cites [35] Waxmonsky JG Waschbusch DA Babinski DE Does pharmacological treatment of ADHD in adults enhance parenting performance? results of a double-blind randomized trial. CNS Drugs. 2014; 28: 665– 677. 24796970 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

In Weisler et al, end point ADHD-RS-IV scores decreased in both children and adults, and age-by-sex subgroup analysis noted both symptoms of inattention and hyperactivity/impulsivity decreased with active treatment in all subgroups.

“The end point ADHD-RS-IV scores decreased in both children and adults, and the age-by-sex subgroup analysis noted both symptoms of inattention and hyperactivity/impulsivity decreased with active treatment in all subgroups.”

• cites [45] Weisler RH Adler LA Kollins SH Analysis of individual items on the attention-deficit/hyperactivity disorder symptom rating scale in children and adults: the effects of age and sex in pivotal trials of lisdexamfetamine dimesylate. Neuropsychiatr Dis Treat. 2014; 10: 1– 12. 24363557 PMC3862743 sourceCould not verify

  The Introduction says generally that stimulants reduce core ADHD symptoms, and the References list a Weisler study in adults, but neither passage reports endpoint ADHD-RS-IV scores. Searches for ADHD-RS-IV and age-by-sex subgroup results found no passage in our copy addressing the claimed decreases in both symptom categories across all subgroups; page numbers were not available. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

May combine two claims.

In short-term trials, the most commonly reported adverse event in patients receiving LDX was decreased appetite, reported at 26.5% and 32.9%, although weight loss was not consistently reported.

“The most commonly reported adverse event in patients who received LDX during the short-term trials was a decrease in appetite, reported at 26.5%22 and 32.9%,23 although weight loss was not consistently reported in these trials.”

• cites [22] 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: 1364– 1374. 19012818 sourceNot checked — no full text of the source
• cites [23] 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: 694– 702. 23945447 sourcePartly supported

  The Discussion identifies decreased appetite as a common adverse event in this LDX study, and Results > Safety reports weight decrease as an adverse event in 3.5% of subjects during dose optimization but none during crossover. The available passages do not establish that decreased appetite was the most common event or occurred in 32.9% of subjects. The 26.5% figure is attached to a different citation in the citing sentence. (LLM, conf=0.81)

  Experimental — accuracy not yet measured

May combine two claims.

No histopathologic changes have been noted in any studies with LDX, and toxicology findings are unremarkable and consistent with changes in behavioral activity associated with stimulant exposure, as is loss of appetite and reductions in weight gain and growth measurements.

“No histopathologic changes have been noted in any studies with LDX, and findings regarding toxicology are unremarkable and consistent with changes in behavioral activity associated with stimulant exposure, as is loss of appetite and reductions in weight gain and growth measurements.16”

• cites [16] Hutson PH Pennick M Secker R. Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug. Neuropharmacology. 2014; 87: 41– 50. 24594478 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

In the subgroup of men and women aged 40 to 55 years, end point mean item scores also decreased, although with more variability, as decreases were also noted in the placebo groups.

“and in the subgroup of men and women aged 40 to 55 years, the end point mean item scores also decreased, although with more variability, as decreases were also noted in the placebo groups.”

• cites [45] Weisler RH Adler LA Kollins SH Analysis of individual items on the attention-deficit/hyperactivity disorder symptom rating scale in children and adults: the effects of age and sex in pivotal trials of lisdexamfetamine dimesylate. Neuropsychiatr Dis Treat. 2014; 10: 1– 12. 24363557 PMC3862743 sourceCould not verify

  The Sleep section reports a decrease in overall sleep-quality scores for adults receiving lisdexamfetamine and placebo, but does not report mean item scores for a 40–55-year-old subgroup. The short-term-trials tables cover adults aged 18–55 and report vital signs, not the claimed item-score pattern. Searches for the subgroup, item scores, and placebo-group variability found no passage addressing the claim. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

Dry mouth was commonly reported by adults (up to 32%), whereas less than 6% of children and adolescents reported this adverse event.

“However, dry mouth was commonly reported by adults (up to 32%),23 whereas less than 6% of children and adolescents reported this adverse event.46”

• cites [23] 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: 694– 702. 23945447 sourceSupported
• cites [46] Coghill DR Caballero B Sorooshian S Civil R. A systematic review of the safety of lisdexamfetamine dimesylate. CNS Drugs. 2014; 28: 497– 511. 24788672 PMC4057639 sourceSupported

May combine two claims.

Other commonly reported adverse events in short-term trials were insomnia (11%-19%) and nausea (2.5%-12.5%).

“Other commonly reported adverse events were insomnia (11%-19%), and nausea (2.5%-12.5%).”

• cites [22] 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: 1364– 1374. 19012818 sourceNot checked — no full text of the source
• cites [23] 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: 694– 702. 23945447 sourcePartly supported

  The Results > Safety section (Table 4; page unavailable) reports insomnia in 18.3% and nausea in 7.7% of adults during dose optimization, both within the claimed ranges. This study does not establish the full 11%–19% and 2.5%–12.5% ranges across short-term trials; its crossover-phase rates were lower. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

In a post hoc analysis of Biederman et al, at week 6 compared with placebo, LDX was associated with significantly lower DBQ errors (P < .02) and lapses (P < .02).

“At week 6, compared with placebo, LDX was associated with significantly lower DBQ errors (P < .02) and lapses (P < .02).”

• cites [44] 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: 601– 607. 23174471 sourceCould not verify

  The Methods (Study overview; page unavailable) describe two 4-week trials, and the reported outcomes are ADHD-RS-IV item scores, not DBQ errors or lapses. Searches for “DBQ errors lapses week 6” and “Biederman driving behavior questionnaire” found no passage reporting the claimed week-6 comparison or P values. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

In postmarketing surveillance from 9525 adverse events associated with LDX reported to FDA between January 2004 and March 2017, 11 cases (0.12%) of cardiomyopathy were reported; most were men, aged 10 to 19 years, taking the drug for 6 to 12 months.

“In a postmarketing surveillance from a total of 9525 adverse events associated with LDX reported to the FDA between January 2004 and March 2017, 11 cases (0.12%) of cardiomyopathy were reported; most were men, aged 10 to 19 years of age, taking the drug for 6 to 12 months.50”

• cites [50] Vyvanse and Cardiomyopathy—from FDA reports. Ehealthme.com, 3 2017 http://www.ehealthme.com/ds/vyvanse/cardiomyopathy/. Accessed March 15, 2017. sourceCould not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

As d-amphetamine is released slowly from the prodrug LDX, it does not produce the subjective "rush" experienced by drug abusers and may offer reduced abuse potential relative to immediate-release d-amphetamine.

“As d-amphetamine is released slowly from the prodrug LDX, it does not produce the subjective “rush” experienced by drug abusers and may offer reduced abuse potential relative to immediate-release d-amphetamine.16”

• cites [16] Hutson PH Pennick M Secker R. Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug. Neuropharmacology. 2014; 87: 41– 50. 24594478 sourcePartly supported

  The Conclusions and Safety sections report slower d-amphetamine exposure, lower drug-liking scores at equivalent doses, and a possible reduction in abuse potential compared with immediate-release d-amphetamine. They do not support the categorical statement that LDX produces no subjective “rush”: the Safety section reports significant drug-liking at a supratherapeutic LDX dose. Page numbers are not available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Surveys using the RADARS system in the United States noted the abuse potential of LDX to be very low, with no increases demonstrated between 2007 and 2011.

“Surveys using the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) system in the United States noted the abuse potential of LDX to be very low, with no increases demonstrated between 2007 and 2011.52”

• cites [52] Sembower MA Ertischek MD Buchholtz C Dasgupta N Schnoll SH. Surveillance of diversion and nonmedical use of extended-release prescription amphetamine and oral methylphenidate in the United States. J Addict Dis. 2013; 32: 26– 38. 23480245 PMC3630455 sourcePartly supported

  The Discussion reports low rates of misuse, abuse, and diversion for extended-release stimulants overall, and the Methods list Vyvanse among the amphetamine products studied. The paper does not report a separate trend for LDX. Its Results report significant increases from 2007 to 2011 in extended-release amphetamine poison-center intentional-exposure rates, so the claim that no increases were demonstrated is not supported. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

LDX is an amphetamine prodrug that undergoes a biochemical conversion following administration to its active form, d-amphetamine.

“Lisdexamfetamine dimesylate (LDX) is an amphetamine prodrug that undergoes a biochemical conversion following administration to its active form, d-amphetamine.”

May combine two claims.

The efficacy of LDX over placebo has been demonstrated in several studies in adults with moderate to severe ADHD, with significant improvements in ADHD rating scales, Clinical Global Improvement scores, and assessments of executive function for all doses of LDX 30-70 mg daily.

“The efficacy of LDX over placebo has been demonstrated in several studies in adults with moderate to severe ADHD with significant improvements noted in ADHD rating scales, Clinical Global Improvement scores, and assessments of executive function, for all doses of LDX (30-70 mg daily).”

May combine two claims.

Long-acting preparations improve compliance and may decrease the potential for abuse, misuse, or recreational use.

“Long-acting preparations improve compliance and may decrease the potential for abuse, misuse, or recreational use.”

• cites [8] Wilens TE Adler LA Adams J Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry. 2008; 47: 21– 31. 18174822 sourceNot checked — no full text of the source

May combine two claims.

LDX is a water-soluble prodrug of the single isomer d-amphetamine and l-lysine that remains pharmacologically inactive until enzymatic hydrolysis predominantly by red blood cells converts it to d-amphetamine.

“Lisdexamfetamine dimesylate is a water-soluble prodrug of the single isomer—d-amphetamine and l-lysine—that remains pharmacologically inactive until it undergoes enzymatic hydrolysis predominantly by red blood cells converting the pharmacologically inactive molecule to the active drug moiety, d-amphetamine.”

• cites [15] Pennick M. Metabolism of the prodrug lisdexamfetamine dimesylate in human red blood cells from normal and sickle cell disease donors. J Drug Assess. 2013; 2: 17– 20. 27536433 PMC4937656 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Lisdexamfetamine dimesylate (LDX) is the first prodrug stimulant used for the treatment of attention-deficit/hyperactivity disorder (ADHD) dosed once daily.

“Lisdexamfetamine dimesylate (LDX) is the first prodrug stimulant used for the treatment of attention-deficit/hyperactivity disorder (ADHD) dosed once daily.”

May combine two claims.

The sustained efficacy of LDX throughout the day and into the evening hours demonstrates its benefit as one of the longest acting stimulant preparations, making it a viable treatment option in managing ADHD symptoms throughout the day.

“The sustained efficacy of LDX throughout the day and into the evening hours demonstrated its benefit as one of the longest acting stimulant preparations, making it a viable treatment option in managing ADHD symptoms throughout the day.”

May combine two claims.

Long-term release of LDX results in a homogeneous action, allowing for a similar effect noted 90 minutes to 14 hours after administration.

“The long-term release of the drug results in a homogeneous action, allowing for a similar effect noted 90 minutes to 14 hours after administration.”

• cites [18] Childress AC Sallee FR. The use of lisdexamfetamine dimesylate for the treatment of ADHD. Expert Rev Neurother. 2012; 12: 13– 26. 22243042 sourceNot checked — no full text of the source

May combine two claims.

Following administration, conversion of LDX to d-amphetamine occurs in approximately 1.5 hours, with duration from 1.5 to 13 hours in children and 2 to 14 hours in adults.

“Following administration, conversion of LDX to d-amphetamine occurs in approximately 1.5 hours, with duration from 1.5 to 13 hours in children and 2 to 14 hours in adults.”

• cites [9] Brams M Moon E Pucci M López FA. Duration of effect of oral long-acting stimulant medications for ADHD throughout the day. Curr Med Res Opin. 2010; 26: 1809– 1825. 20491612 sourceNot checked — no full text of the source
• cites [17] Ermer JC Pennick M Frick G. Lisdexamfetamine dimesylate: prodrug delivery, amphetamine exposure and duration of efficacy. Clin Drug Investig. 2016; 36: 341– 356. PMC4823324 27021968 sourceNot checked — no full text of the source

May combine two claims.

In the Wigal et al trial, ADHD-RS-IV total scores improved from baseline and CGI-I scores suggested that 76.5% of participants improved while taking LDX and 23.1% improved on placebo.

“The ADHD-RS-IV total scores improved from baseline (P < .0001) and the CGI-I scores suggested that 76.5% of participants improved while taking LDX and 23.1% of participants improved on placebo (P < .0001).”

• cites [24] Wigal T Brams M Gasior M Gao J Squires L Giblin J. 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 sourceNot checked — no full text of the source

May combine two claims.

Acidic drugs such as ascorbic acid may decrease levels of d-amphetamine, and basic drugs such as sodium bicarbonate may increase levels of d-amphetamine.

“acidic drugs (eg, ascorbic acid) may decrease levels of d-amphetamine; likewise, basic drugs (eg, sodium bicarbonate) may increase levels of d-amphetamine”

May combine two claims.

The first trial by Adler et al established the efficacy of LDX in adults and resulted in LDX being the first ADHD medication approved by the FDA for adults in the United States.

“The first trial by Adler et al22 established the efficacy of LDX in adults and resulted in LDX being the first ADHD medication approved by the Food and Drug Administration (FDA) for adults in the United States.”

• cites [22] 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: 1364– 1374. 19012818 sourceNot checked — no full text of the source

May combine two claims.

Levels of d-amphetamine are proportional to the LDX dose, exhibiting low intraindividual and interindividual variability.

“Levels of d-amphetamine are proportional to the LDX dose, exhibiting low intraindividual and interindividual variability.”

• cites [19] Comiran E Kessler FH Fröehlich PE Limberger RP. Lisdexamfetamine: a pharmacokinetic review. Eur J Pharm Sci. 2016; 89: 172– 179. 27125257 sourceNot checked — no full text of the source

May combine two claims.

Food does not affect the observed area under the curve or peak plasma concentration of LDX but prolongs time to peak plasma concentration by approximately 1 hour.

“Food does not affect the observed area under the curve or peak plasma concentration but does prolong time to peak plasma concentration by approximately 1 hour.”

May combine two claims.

Another post hoc analysis of the AWE study noted that LDX significantly improved overall QOL at study end point compared with baseline, and no significant differences were observed in either age or sex.

“Another post hoc analysis of the AWE study assessed improvements in QOL using patient-reported AIM-A, a QOL assessment consisting of 4 global items, 5 multi-item subscales compromising 6 domains and 5 economic impact items, and noted that LDX significantly improved overall QOL at study end point compared with baseline, and no significant differences were observed in either age or sex.”

• cites [38] Brams M Giblin J Gasior M Gao J Wigal T. Effects of open-label lisdexamfetamine dimesylate on self-reported quality of life in adults with ADHD. Postgrad Med. 2011; 123: 99– 108. 21566420 sourceNot checked — no full text of the source

May combine two claims.

The active moiety of LDX crosses the blood-brain barrier and increases noradrenergic and dopaminergic neurotransmission, thereby exerting its therapeutic effects.

“The active moiety crosses the blood-brain barrier and increases noradrenergic and dopaminergic neurotransmission thereby exerting its therapeutic effects.”

• cites [17] Ermer JC Pennick M Frick G. Lisdexamfetamine dimesylate: prodrug delivery, amphetamine exposure and duration of efficacy. Clin Drug Investig. 2016; 36: 341– 356. PMC4823324 27021968 sourceNot checked — no full text of the source

May combine two claims.

A post hoc analysis of the Wigal et al trial noted least squares mean effect sizes of 0.9 for PERMP-A and 0.8 for PERMP-C for all post dose sessions, and medium to large effect sizes with LDX were maintained from 2 to 14 hours for all PERMP assessments.

“A post hoc analysis of this study noted LS mean effect sizes of 0.9 for PERMP-A and 0.8 for PERMP-C for all post dose sessions, and medium to large effect sizes with LDX were maintained from 2 to 14 hours for all PERMP assessments.”

• cites [37] Wigal T Brams M Gasior M Gao J Giblin J. Effect size of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. Postgrad Med. 2011; 123: 169– 176. 21474905 sourceNot checked — no full text of the source

May combine two claims.

In the 4-week Adler et al trial, all doses of LDX demonstrated significant improvements in ADHD-RS-IV scores and CGI-I scores compared with placebo.

“At study end point, compared with baseline, all doses of LDX demonstrated significant improvements in ADHD Rating Scale Version-IV (ADHD-RS-IV) scores and in Clinical Global Impressions Improvement (CGI-I) scores, compared with placebo (P < .0001; P < .01, respectively).”

• cites [22] 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: 1364– 1374. 19012818 sourceNot checked — no full text of the source

May combine two claims.

In that post hoc analysis, for AAQoL, the least squares mean difference for total score was 21, and improvement was observed from baseline with LDX compared with placebo for all AAQoL subscales.

“for AAQoL, the least squares (LS) mean difference for total score was 21, and improvement was observed from baseline with LDX compared with placebo for all AAQoL subscales”

• cites [33] Adler LA Dirks B Deas P Self-reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study. BMC Psychiatry. 2013; 13: 253. 24106804 PMC3854089 sourceNot checked — no full text of the source

May combine two claims.

In patients in whom ADHD symptoms may not be optimally managed with amphetamines, LDX may be a potential alternative because efficacy outcomes in prior amphetamine-treated patients were consistent with those of the overall study population.

“Thus, patients in whom ADHD symptoms may not be optimally managed with amphetamines, LDX may be a potential alternative as efficacy outcomes in prior amphetamine-treated patients were consistent with those of the overall study population.”

May combine two claims.

Both LDX and d-amphetamine are renally eliminated and are not dialyzable.

“Both LDX and d-amphetamine are renally eliminated and are not dialyzable”

• cites [19] Comiran E Kessler FH Fröehlich PE Limberger RP. Lisdexamfetamine: a pharmacokinetic review. Eur J Pharm Sci. 2016; 89: 172– 179. 27125257 sourceNot checked — no full text of the source

May combine two claims.

In a 14-week trial comparing LDX up to 70 mg/d with MAS-IR up to 45 mg/d, both treatments resulted in significant improvements in the primary outcome measure of ADHD-RS scores and did not differ significantly from each other: LDX at 48.7% and MAS-IR at 45.1%.

“Both treatments resulted in significant improvements in the primary outcome measure of ADHD-RS scores and did not differ significantly from each other: LDX at 48.7% and MAS-IR at 45.1%.”

• cites [27] Adler LA Alperin S Leon T Faraone S. Clinical effects of lisdexamfetamine and mixed amphetamine salts immediate release in adult ADHD: results of a crossover design clinical trial. Postgrad Med. 2014; 126: 17– 24. 25295646 sourceNot checked — no full text of the source

May combine two claims.

In a double-blind, placebo-controlled crossover study in college students with ADHD, LDX relative to no medication baseline and placebo was associated with significant reductions in ADHD symptoms (CAARS) and improvement in executive functioning for nearly all BRIEF-A subscales (both P < .001), with similar effects for psychosocial functioning (SCL-90-R) (P < .02).

“LDX relative to no medication baseline and placebo was associated with significant reductions in ADHD symptoms as assessed via Conners’ Adult ADHD Rating Scales (CAARS) and improvement in executive functioning for nearly all BRIEF-A subscales (both, P < .001), with similar effects for psychosocial functioning, using the Symptom Checklist 90-Revised (SCL-90-R) (P < .02).”

• cites [32] 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: 202– 220. 22166471 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

CDR-CBT is a set of standardized, validated neuropsychometric tasks for assessing cognitive function in adults with ADHD.

“the Cognitive Drug Research-Computerized Battery of Tests (CDR-CBT), a set of standardized, validated neruopsychometric tasks, for assessing cognitive function in adults with ADHD”

• cites [26] Martin PT Corcoran M Zhang P Katic A. Randomized, double-blind, placebo-controlled, crossover study of the effects of lisdexamfetamine dimesylate and mixed amphetamine salts on cognition throughout the day in adults with attention-deficit/hyperactivity disorder. Clin Drug Investig. 2014; 34: 147– 157. PMC3899471 24297663 sourceNot checked — no full text of the source

May combine two claims.

In the Brams et al withdrawal study, at baseline ADHD-RS-IV scores were similar in patients randomized to LDX or placebo and significantly improved in patients treated with LDX vs placebo.

“At baseline, ADHD-RS-IV scores were similar in patients randomized to LDX or placebo and significantly improved in patients treated with LDX vs placebo (P < .0001).”

• cites [29] 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: 977– 983. 22780921Not checked — no full text of the source

May combine two claims.

In that post hoc analysis, as CGI-S scores increased, ADHD symptoms increased, with a positive linear relationship among ADHD symptoms and global illness ratings.

“As the CGI-S scores increased (ie, worsened), so did the ADHD symptoms, with a positive linear relationship among ADHD symptoms and global illness ratings, correlating a dependence factor between the two.”

• cites [39] Weisler RH Babcock T Adeyi B Brams M. Relationship of ADHD symptoms and global illness severity in adults treated with lisdexamfetamine dimesylate. Postgrad Med. 2014; 126: 31– 41. 25295648 sourceNot checked — no full text of the source

May combine two claims.

In a 12-month open-label extension, LDX produced greater clinical response and symptom improvement in patients with greater baseline symptom severity.

“This long-term extension study demonstrated LDX’s increased degree of clinical response and symptom improvement in patients with greater baseline symptom severity.”

• cites [34] Ginsberg L Katic A Adeyi B Long-term treatment outcomes with lisdexamfetamine dimesylate for adults with attention-deficit/hyperactivity disorder stratified by baseline severity. Curr Med Res Opin. 2011; 27: 1097– 1107. 21438796 sourceNot checked — no full text of the source

May combine two claims.

A post hoc analysis of the Weisler et al trial noted that LDX was effective in improving symptoms of ADHD in patients who exhibited predominantly inattention, hyperactivity/impulsivity, or combined symptom clusters, and clinical response did not differ among these groups.

“A post hoc analysis of this trial noted that LDX was effective in improving symptoms of ADHD in patients who exhibited predominantly inattention, hyperactivity/impulsivity, or combined symptom clusters, and clinical response did not differ among these different groups exhibiting specific predominant subtype symptoms.”

• cites [30] 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: 22– 30. PMC3398683 22808446 sourceNot checked — no full text of the source

May combine two claims.

In the Weisler et al extension study, at end point, 84.1% of patients noted an improvement in overall functioning as measured by CGI-I, with similar responses in prior LDX-treated and LDX-naïve patients (84.8% and 79.6%, respectively).

“at end point, 84.1% of patients noted an improvement in overall functioning as measured by the CGI-I, with similar responses noted in both the prior LDX-treated patients and LDX-naïve patients (84.8% and 79.6%, respectively).”

• 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: 573– 585. 20095369 sourceNot checked — no full text of the source

May combine two claims.

Brams et al conducted a 6-week placebo-controlled, randomized, withdrawal study and provided evidence of long-term efficacy of LDX in adults.

“Brams et al29 conducted a 6-week placebo-controlled, randomized, withdrawal study and provided evidence of long-term efficacy of LDX in adults.”

• cites [29] 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: 977– 983. 22780921Not checked — no full text of the source

May combine two claims.

Patients from the short-term and long-term trials at study end point achieved clinical response (≥30% decrease in ADHD-RS-IV and CGI-I score of 1 or 2) in 78.9% to 88.4% and symptomatic remission (ADHD-RS-IV ≤18) in 64.0% to 72.1%.

“Patients from the short-term trial22 and the long-term trial28 at study end point demonstrated increased symptom improvement as noted by clinical response criteria achieved by 78.9% to 88.4% and symptomatic remission achieved by 64.0% to 72.1% of participants.”

• cites [34] Ginsberg L Katic A Adeyi B Long-term treatment outcomes with lisdexamfetamine dimesylate for adults with attention-deficit/hyperactivity disorder stratified by baseline severity. Curr Med Res Opin. 2011; 27: 1097– 1107. 21438796 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

The delayed 1-hour difference in efficacy onset noted between MAS-IR and LDX may necessitate an earlier administration of LDX in some patients.

“The delayed 1-hour difference in efficacy onset noted between MAS-IR and LDX may necessitate an earlier administration of LDX in some patients.”

May combine two claims.

Specific aspects of executive functioning improved with LDX were BRI, MCI, GEC, including inhibition, initiation, working memory, planning and organizing, task management, and organization of materials.

“Specific aspects of executive functioning, which improved with LDX, were noted for BRI, MCI, GEC, including inhibition, initiation, working memory, planning and organizing, task management, and organization of materials.”

• cites [32] 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: 202– 220. 22166471 sourceNot checked — no full text of the source

May combine two claims.

LS mean treatment differences for BRIEF-A GEC, BRI, and MCI showed significant improvement with LDX over placebo: −11.2, −8.4, and −11.6, respectively, all P ≤ .0002.

“The LS mean treatment difference for GEC, BRI, and MCI noted significant improvement with LDX over placebo at −11.2, −8.4, and −11.6, respectively, all P’s ≤ .0002).”

• cites [40] Weisler R Ginsberg L Dirks B Deas P Adeyi B Adler LA. Treatment with lisdexamfetamine dimesylate improves self- and informant-rated executive function behaviors and clinician- and informant-rated ADHD symptoms in adults: data from a randomized, double-blind, placebo-controlled study [published online ahead of print 1 24, 2014]. J Atten Disord. doi: 10.1177/1087054713518242. 24464328 sourceNot checked — no full text of the source

May combine two claims.

In a post hoc analysis of the AWE study, at study end point BADDS total and cluster scores were significantly reduced from baseline (P < .0001), 62.7% had BADDS total <50, and 78.9% reliably improved versus 1.4% reliably worsened.

“At study end point, BADDS total and cluster scores were significantly reduced compared with baseline (P < .0001), and 62.7% of participants had a BADDS total score <50 with 78.9% reliably improved compared with 1.4% reliably worsened.”

• cites [41] 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. 2010; 122: 7– 17. 20861583 sourceNot checked — no full text of the source

May combine two claims.

Informant-rated EF deficits, using BRIEF-A GEC and Index T scores, improved significantly more with LDX compared with placebo and in a similar manner to self-reported EF deficits.

“Informant-rated EF deficits, using BRIEF-A GEC and Index T scores, improved significantly more with LDX compared with placebo treatment and in a similar manner to self-reported EF deficits.”

• cites [40] Weisler R Ginsberg L Dirks B Deas P Adeyi B Adler LA. Treatment with lisdexamfetamine dimesylate improves self- and informant-rated executive function behaviors and clinician- and informant-rated ADHD symptoms in adults: data from a randomized, double-blind, placebo-controlled study [published online ahead of print 1 24, 2014]. J Atten Disord. doi: 10.1177/1087054713518242. 24464328 sourceNot checked — no full text of the source

May combine two claims.

In the Martin et al pilot study, the primary outcome composite power of attention score improved with both stimulants compared with placebo, and improvements were first noted 2 and 3 hours post dose with MAS-IR and LDX, respectively, and persisted for up to 16 hours post dose, with maximum reductions with both stimulants occurring 5 hours post dose at day 7.

“The primary outcome, the composite power of attention score improved with both stimulants compared with placebo, and improvements were first noted 2 and 3 hours post dose with MAS-IR and LDX, respectively, and persisted for up to 16 hours post dose, with maximum reductions with both stimulants occurring 5 hours post dose at day 7.”

• cites [26] Martin PT Corcoran M Zhang P Katic A. Randomized, double-blind, placebo-controlled, crossover study of the effects of lisdexamfetamine dimesylate and mixed amphetamine salts on cognition throughout the day in adults with attention-deficit/hyperactivity disorder. Clin Drug Investig. 2014; 34: 147– 157. PMC3899471 24297663 sourceNot checked — no full text of the source

May combine two claims.

Ermer et al evaluated safety of LDX in healthy older adults and noted the drug's safety profile was consistent with prior data in healthy younger adults aged 18 to 55 years.

“Ermer et al20 evaluated the safety of LDX in healthy older adults and noted that the drug’s safety profile was consistent with prior data in healthy younger adults aged 18 to 55 years.”

• cites [20] Ermer J Haffey MB Richards C Double-blind, placebo-controlled, two-period, crossover trial to examine the pharmacokinetics of lisdexamfetamine dimesylate in healthy older adults. Neuropsychiatr Dis Treat. 2013; 9: 219– 229. 23431065 PMC3575217 sourceNot checked — no full text of the source

May combine two claims.

LDX compared with placebo from baseline to study end point was associated with small but significant increases in pulse (mean change: 15.8, P < .001) and QTc interval (mean change: 9.7, P = .01), although no serious adverse events were reported.

“Likewise, LDX compared with placebo from baseline to study end point was associated with small but significant increases in pulse (mean change: 15.8, P < .001) and QTc interval (corrected QT interval) (mean change: 9.7, P = .01), although no serious adverse events were reported during the study period.31”

• cites [31] 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: 484– 491. 22277301 sourceNot checked — no full text of the source

May combine two claims.

In a double-blind, placebo-controlled trial in young adults with ADHD, compared with placebo, posttreatment with LDX improved reaction time across 5 surprise events, significantly reduced accidents, produced significantly faster reaction times (91% faster), and lower rate of simulated driving collisions.

“Compared with placebo, posttreatment with LDX revealed positive effect on reaction time across 5 surprise events and significantly fewer accidents.”

• Also stated in: § Driving Performance · plain

  “In addition, compared with placebo, LDX was associated with significantly faster reaction times (91% faster) and lower rate of simulated driving collisions.”

• cites [31] 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: 484– 491. 22277301 sourceNot checked — no full text of the source

May combine two claims.

In that study, a decrease in left ventricular dimensions was observed; however, a more sensitive measure of LV size, a change in LV volume, was not noted.

“A decrease in left ventricular (LV) dimensions was observed; however, a more sensitive measure of LV size, a change in LV volume, was not noted.”

• cites [48] Hammerness P Zusman R Systrom D A cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder. World J Biol Psychiatry. 2013; 14: 299– 306. 22559155 sourceNot checked — no full text of the source

May combine two claims.

In Babinski et al, LDX was associated with a large increase in verbalizations and moderate decrease in ratio of commands to verbalizations as well as an increase in total commands with little change in verbalizations, resulting in an increase in the ratio of commands to total verbalizations.

“Lisdexamfetamine dimesylate was associated with a large increase in verbalizations and moderate decrease in ratio of commands to verbalizations as well as an increase in total commands with little change in verbalizations, resulting in an increase in the ratio of commands to total verbalizations.”

• cites [43] Babinski DE Waxmonsky JG Waschbusch DA A pilot study of stimulant medication for adults with attention-deficit/hyperactivity disorder (ADHD) who are parents of adolescents with ADHD: the acute effects of stimulant medication on observed parent-adolescent interactions. J Child Adolesc Psychopharmacol. 2014; 24: 582– 585. 25386742 PMC4268552 sourceNot checked — no full text of the source

May combine two claims.

In that trial, TEAEs with incidence ≥5% in the stimulant-treated group compared with placebo were headache (14.3% vs 5%), insomnia (5.4% vs 5%), and upper respiratory tract infection (8.9% vs 0%).

“Treatment emergent adverse events with incidence ≥5% in the stimulant-treated group compared with placebo were headache (14.3% vs 5%), insomnia (5.4% vs 5%), and upper respiratory tract infection (8.9% vs 0%).29”

• cites [29] 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: 977– 983. 22780921Not checked — no full text of the source

May combine two claims.

During the open-label extension study, 87.7% of patients experienced adverse events, and similar percentages were noted between LDX-naïve patients and those who had received LDX previously.

“During the open-label extension study,28 87.7% of patients experienced adverse events, and similar percentages were noted between LDX-naïve patients and those who had received LDX previously.”

• 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: 573– 585. 20095369 sourceNot checked — no full text of the source

May combine two claims.

Headache and nasopharyngitis were reported in trials, but their frequency was similar to placebo-treated groups.

“Although headache and nasopharyngitis were reported in trials, their frequency was similar to that observed in the placebo-treated groups.”

May combine two claims.

In Babinski et al, statistically significant effects were noted during tasks 2 and 3, associated with problem discussion and homework assignment, respectively.

“Statically significant effects were noted during tasks 2 and 3, associated with problem discussion and homework assignment, respectively.”

• cites [43] Babinski DE Waxmonsky JG Waschbusch DA A pilot study of stimulant medication for adults with attention-deficit/hyperactivity disorder (ADHD) who are parents of adolescents with ADHD: the acute effects of stimulant medication on observed parent-adolescent interactions. J Child Adolesc Psychopharmacol. 2014; 24: 582– 585. 25386742 PMC4268552 sourceNot checked — no full text of the source

May combine two claims.

In Ermer et al, maximal mean increases in pulse in patients aged 55 to 64 years and 65 to 74 years occurred 12 hours post dose and 5.5 hours post dose in patients aged ≥75 years.

“Maximal mean increases in pulse in patients aged 55 to 64 years and 65 to 74 years occurred 12 hours post dose and 5.5 hours post dose in patients aged ≥75 years.”

• cites [20] Ermer J Haffey MB Richards C Double-blind, placebo-controlled, two-period, crossover trial to examine the pharmacokinetics of lisdexamfetamine dimesylate in healthy older adults. Neuropsychiatr Dis Treat. 2013; 9: 219– 229. 23431065 PMC3575217 sourceNot checked — no full text of the source

May combine two claims.

LDX was associated with predictable but modest increases in pulse and heart rate (both P < .05), beginning at week 2 and persisting through week 4, with no meaningful effects on ECG parameters such as PR, PP, and QT intervals.

“Although LDX was associated with predictable but modest increases in pulse and heart rate (both, P < .05), beginning at week 2 and persisting through week 4, no meaningful effects on electrocardiogram (ECG) parameters such as PR, PP, and QT intervals were noted.”

• cites [49] Adler LA Weisler RH Goodman DW Hamdani M Niebler GE. Short-term effects of lisdexamfetamine dimesylate on cardiovascular parameters in a 4-week clinical trial in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2009; 70: 1652– 1661. 20141706 sourceNot checked — no full text of the source

May combine two claims.

Postmarketing safety data are consistent with earlier reported adverse events, and poison centers have reported patients presenting with insomnia, dystonia, hallucinations, jitters, tachycardia, and chest pain.

“Postmarketing safety data are consistent with the earlier reported adverse events, and poison centers have reported patients presenting with insomnia, dystonia, hallucinations, jitters, tachycardia, and chest pain.47”

• cites [47] Spiller HA Griffith JR Anderson DL Weber JA Aleguas A. Poison centers detect an unexpectedly frequent number of adverse drug reactions to lisdexamfetamine. Ann Pharmacother. 2008; 42: 1142– 1143. 18594051 sourceNot checked — no full text of the source

May combine two claims.

In Ermer et al, no vital sign differences were noted between men and women, and no trends in pulse or blood pressure changes were observed according to age.

“No vital sign differences were noted between men and women, and no trends in pulse or blood pressure changes were observed according to age.”

• cites [20] Ermer J Haffey MB Richards C Double-blind, placebo-controlled, two-period, crossover trial to examine the pharmacokinetics of lisdexamfetamine dimesylate in healthy older adults. Neuropsychiatr Dis Treat. 2013; 9: 219– 229. 23431065 PMC3575217 sourceNot checked — no full text of the source

May combine two claims.

In Babinski et al task 1 (neutral discussion), parents on LDX displayed a lower command to verbalization ratio, statistically significant (P = .04), associated with a large decrease in commands and moderate increases in verbalizations and responsiveness, although the latter were not significant.

“Task 1 was neutral discussion between parent and child, and parents on LDX displayed a lower command to verbalization ratio, which was statistically significant (P = .04), and associated with a large decrease in the number of commands, and moderate increases in verbalizations and responsiveness, although the latter were not significant.”

• cites [43] Babinski DE Waxmonsky JG Waschbusch DA A pilot study of stimulant medication for adults with attention-deficit/hyperactivity disorder (ADHD) who are parents of adolescents with ADHD: the acute effects of stimulant medication on observed parent-adolescent interactions. J Child Adolesc Psychopharmacol. 2014; 24: 582– 585. 25386742 PMC4268552 sourceNot checked — no full text of the source

May combine two claims.

At maximum exertion, diastolic blood pressure was significantly increased in hypertensive patients (P < .003), but not in healthy subjects.

“At maximum exertion, diastolic blood pressure was significantly increased in hypertensive patients (P < .003), but not in healthy subjects, which may require further studies to elucidate the cause.”

• cites [48] Hammerness P Zusman R Systrom D A cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder. World J Biol Psychiatry. 2013; 14: 299– 306. 22559155 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

LDX has demonstrated low intrapatient and interpatient variability in the systemic exposure of d-amphetamine, with changes in gastric acidity and gastrointestinal transit times having minimal if any impact on the absorption of LDX.

“Lisdexamfetamine dimesylate has demonstrated low intrapatient and interpatient variability in the systemic exposure of d-amphetamine, with changes in gastric acidity and gastrointestinal transit times having minimal if any impact on the absorption of LDX.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Unlike MAS-XR, which requires an acidic environment to dissolve the enteric-coated beads, LDX may be dissolved in water for patients who may have difficulty swallowing the capsule.

“Unlike MAS-XR, which requires an acidic environment to dissolve the enteric-coated beads, LDX may be dissolved in water for patients who may have difficulty swallowing the capsule.”

May combine two claims.

The pooled European location effect size was larger compared with the United States, which may explain the higher effect size, as can changes in study design regarding placebo, and clinical and methodological diversity among studies which may influence estimated effect sizes.

“The pooled European location effect size was larger compared with the United States which may explain the higher effect size, as can changes in study design regarding placebo, and clinical and methodological diversity among studies which may influence estimated effect sizes.”

• cites [53] Fridman M Hodgkins PS Kahle JS Erder MH. Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: estimates based on indirect analysis using a systematic review and meta-regression analysis. Eur Psychiatry. 2015; 30: 521– 527. 25725594 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

LDX is the first prodrug approved for managing ADHD across the life span of children, adolescents, and adults.

“Lisdexamfetamine dimesylate is the first prodrug approved for managing ADHD across the life span of children, adolescents, and adults.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

LDX, unlike atomoxetine, is not metabolized by CYP450 enzymes, thus has a low potential for interacting with other drugs affected by the isoenzymes.

“In addition, LDX, unlike atomoxetine, is not metabolized by CYP450 enzymes, thus has a low potential for interacting with other drug affected by the isoenzymes.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

LDX's long duration of effect allows for once-daily dosing encouraging medication compliance while also providing sufficient efficacy for the average work or school day.

“Its long duration of effect allows for once-daily dosing encouraging medication compliance while also providing sufficient efficacy for the average work or school day.”

• AssumptionRests on an assumption: A duration of effect up to 14 hours is sufficient to cover the average work or school day.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The drug carries a warning that misuse of amphetamines may cause sudden death and serious cardiovascular adverse events, and caution is indicated in treating patients with preexisting hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.

“However, the drug carries a warning that misuse of amphetamines may cause sudden death and serious cardiovascular adverse events, and caution is indicated in treating patients with preexisting hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Misuse of amphetamine stimulants may cause sudden death and serious cardiovascular adverse events.

“In addition, misuse of amphetamine stimulants may cause sudden death and serious cardiovascular adverse events.”

May combine two claims.

Compared with other stimulants, LDX demonstrates a more moderate reinforcing effect in drug self-administration and a more time-dependent effect in drug discrimination studies.

“Compared with other stimulants, LDX demonstrates a more moderate reinforcing effect in drug self-administration and a more time-dependent effect in drug discrimination studies.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

As with other stimulants, a black box warning addressing the potential for abuse and dependence exists with LDX, a class II-controlled substance.

“As with other stimulants, a black box warning addressing the potential for abuse and dependence exists with LDX, a class II–controlled substance”

May combine two claims.

LDX is chemically stable in water and at room temperature and resistant to buffering even under extreme hydrolytic conditions, making alteration of the LDX molecule difficult, costly, and laborious.

“Lisdexamfetamine dimesylate is chemically stable in water and at room temperature and resistant to buffering even under extreme hydrolytic conditions, making alteration of the LDX molecule difficult, costly, and laborious.13”

• cites [13] Alda JA Soutullo C Ramos-Quiroga JA Expert recommendation: contributions to clinical practice of the new prodrug lisdexamfetamine dimesylate (LDX) in the treatment of attention deficit hyperactivity disorder (ADHD). Actas Esp Psiquiatr. 2014; 42: 1– 16. 25644658Not checked — no full text of the source

May combine two claims.

Due to the increase in noradrenergic and dopaminergic neurotransmission, sympathomimetic effects including increases in blood pressure and pulse may occur, changes in vital signs are usually small, and changes in ECG are not clinically relevant.

“Due to the increase in noradrenergic and dopaminergic neurotransmission, sympathomimetic effects including increases in blood pressure and pulse may occur, changes in vital signs are usually small, and changes in ECG are not clinically relevant.”

May combine two claims.

Stimulants are associated with peripheral vasculopathy and patients with Raynaud's phenomenon may be at increased risk for complications.

“Likewise, stimulants are associated with peripheral vasculopathy and patients with Raynaud’s phenomenon may be at increased risk for complications.”