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Cited by 16Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatment

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

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Martin, Patrick T., Corcoran, Mary, Zhang, Pinggao, Katic, Alain·2014·Clinical Drug Investigation
DOI 10.1007/s40261-013-0156-zPMC PMC3899471
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Abstract

BACKGROUND: Understanding the nature and time course of the pharmacodynamic effects of attention-deficit/hyperactivity disorder (ADHD) medications is useful. The Cognitive Drug Research Computerized Battery of Tests (CDR-CBT) is a 20-min battery of ten standardized, validated neuropsychometric tasks. OBJECTIVE: This pilot study examined the sensitivity and responsiveness of the CDR-CBT for assessing cognitive function in adults with ADHD prior to and up to 16 h postdose during treatment with lisdexamfetamine dimesylate (LDX) or mixed amphetamine salts immediate release (MAS-IR; various generics available). METHODS: This was a double-blind three-period crossover study. Participants received LDX 50 mg/day, MAS-IR 20 mg/day, and placebo (~7 a.m.) for 7 days each in randomized order. CDR-CBT was administered on day 1 of period 1 and day 7 of each period at scheduled times between -0.5 (predose) and 16 h postdose. Composite power of attention (PoA) score (sum of simple reaction time, choice reaction time, and digit vigilance speed) was the primary outcome measure. The Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S) was administered at baseline and on day 1 of period 1, and days 6 and 7 of each treatment period. Tertiary outcomes included CDR-CBT composite continuity of attention scores, its component task scores, cognitive reaction time, and response variability scores. No inferential statistical comparisons were conducted. Safety assessments included adverse events (AEs) and vital signs. RESULTS: This analysis included 18 participants (mean age 30.8 years); one withdrew because of AEs. Mean pretreatment PoA scores were 1175.9-1361.2 ms, scores commensurate with a normative age of >40 years. Maximum reductions in PoA scores with LDX and MAS-IR occurred at 5 h postdose at day 7 (least squares mean difference [95% CI] of -150.0 [-235.41 to -64.50] and -79.8 [-165.72 to 6.21] ms vs. placebo, respectively). CAARS-S:S scores were unchanged with LDX and MAS-IR (vs. placebo) at all postdose timepoints. Tertiary attention-related CDR-CBT outcomes were sensitive to LDX and MAS-IR (vs. placebo). Treatment-emergent AEs and vital signs were consistent with previous studies in adult ADHD. CONCLUSION: In adults with ADHD, PoA scores indicated impaired attention at baseline and response to treatment with LDX and MAS-IR (vs. placebo), demonstrating value for measuring the time course of pharmacologic treatment effects.

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  • Additional crossover, open-label trial, and placebo-controlled studies comparing LDX with mixed amphetamine salts immediate-release have demonstrated benefits of the stimulant compared with placebo.

    “Additional crossover, open-label trial,25 as well as placebo-controlled studies comparing LDX with mixed amphetamine salts immediate-release (MAS-IR) tablets have also demonstrated the benefits of the stimulant compared with placebo”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [25]

    Citation 25 is attached to “crossover, open-label trial.” The Methods > Study Design passage identifies this study as a randomized, placebo-controlled, double-blind crossover study—not an open-label trial. Its Conclusions do report improvements in sustained attention with LDX and MAS-IR versus placebo, but that does not support the open-label description. (LLM, conf=0.88)

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  • 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.”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [25]

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  • 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).”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [25]

    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)

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  • 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).”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [25]

    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)

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Cited by

Sorted by citations

Authors
Martin, P. T., Corcoran, M., Zhang, P., & Katic, A.
Affiliations
Takeda (United States) (US)
Corresponding author
Martin, Patrick T.
ORCID
Corcoran, Mary
Venue
Clinical Drug Investigation
Publisher
Springer Science and Business Media LLC
Published
2013-12-03
Volume
34
Issue
2
Pages
147-157
ISSN
  • 0114-2402 (ISSN-L)
  • 1173-2563
  • 1179-1918
DOI
10.1007/s40261-013-0156-z
PMC
PMC3899471
OpenAlex
W2093946202
Cited by
16
References
5
Citations by year
2025: 2 · 2023: 1 · 2022: 2 · 2020: 2 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 1
FWCI
1.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Drug Investigation (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Abbott Laboratories
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • Pfizer
  • AstraZeneca
  • GlaxoSmithKline
  • Sanofi
  • H. Lundbeck A/S
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
lisdexamfetamine dimesylate, mixed amphetamine salts, ADHD medication, cognitive function, attention, reaction time, pharmacodynamics, adult ADHD, stimulant medication effects, sustained attention, response variability, time course of drug effects, placebo response, adverse events, vital signs
MeSH terms
Lisdexamfetamine Dimesylate, Adult, Amphetamines, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Cognition, Dextroamphetamine, Double-Blind Method, Female, Humans, Male, Neuropsychological Tests, Pilot Projects, Psychometrics, Reaction Time, Sensitivity and Specificity, Time Factors, Treatment Outcome, Cross-Over Studies, Young Adult

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