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Cited by 89Attention Deficit Hyperactivity DisorderPharmacology and Obesity TreatmentPharmaceutical studies and practices

A Systematic Review of the Safety of Lisdexamfetamine Dimesylate

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Coghill, David R., Caballero, Beatriz, Sorooshian, Shaw, Civil, Richard·2014·CNS Drugs
DOI 10.1007/s40263-014-0166-2PMC PMC4057639
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Abstract

BACKGROUND: Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). RESULTS: In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX. CONCLUSIONS: The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants.

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Crossref · 10.1007/s40263-014-0166-2

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  • In Weisler et al analysis of similarly designed 4-week trials in children (6-12 years) and adults (18-55 years), inattention items on ADHD-RS-IV were numerically higher than hyperactivity/impulsivity items among older children and adults, especially those aged 40 to 55 years.

    “Weisler et al45 in their analysis of similarly designed 4-week trials in children (aged 6-12 years) and adults (aged 18-55 years) noted that the inattention items on the ADHD-RS-IV rating scales were numerically higher than hyperactivity/impulsivity items among older children and adults, especially those aged 40 to 55 years.”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [45]

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

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  • Overall rates of treatment emergent adverse events for patients treated with LDX were similar across different age groups from previous trials.

    “The overall rates of treatment emergent adverse events (TEAEs) for patients treated with LDX were also similar across the different age groups from previous trials reported.46”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [46]

  • 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”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [46]

  • In adult men and women aged 18 to 39 years, all 18 mean item scores on ADHD-RS-IV decreased numerically in patients treated with LDX compared with placebo.

    “In adult men and women, aged 18 to 39 years, all 18 mean item scores on the ADHD-RS-IV decreased numerically in patients treated with LDX compared with placebo”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [45]

    The Results section describes placebo-controlled LDX trials in adults aged 18–55, but does not report ADHD-RS-IV item scores or results for adults aged 18–39. Searches for the 18 item scores, ADHD-RS-IV, and symptom-score decreases found no passage establishing the claimed comparison. (LLM, conf=0.75)

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  • 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.”

    From Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2017) · cites this paper as [45]

    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)

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Authors
Coghill, D. R., Caballero, B., Sorooshian, S., & Civil, R.
Affiliations
  • University of Dundee (GB)
  • Shire (Switzerland) (CH)
  • Takeda (United States) (US)
Corresponding author
Coghill, David R.
ORCID
Coghill, David R.
Venue
CNS Drugs
Publisher
Springer Science and Business Media LLC
Published
2014-05-01
Volume
28
Issue
6
Pages
497-511
ISSN
  • 1172-7047 (ISSN-L)
  • 1179-1934
DOI
10.1007/s40263-014-0166-2
PMC
PMC4057639
OpenAlex
W2146886967
Cited by
89
References
23
Citations by year
2026: 2 · 2025: 9 · 2024: 9 · 2023: 3 · 2022: 7 · 2021: 10 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 11 · 2016: 6 · 2015: 8
FWCI
1.15
Type
journal article
Language
en
Open access
Licence
Locations
  • CNS Drugs (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
Funders
  • Eli Lilly and Company
  • Pfizer
  • University of Oxford
  • Vifor Pharma
  • Cilag
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
lisdexamfetamine dimesylate, attention deficit hyperactivity disorder, tolerability, treatment-emergent adverse events, insomnia, appetite loss, weight gain, nonmedical use, long-acting stimulants, children and adolescents
MeSH terms
Lisdexamfetamine Dimesylate, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Dextroamphetamine, Dose-Response Relationship, Drug, Humans, Prodrugs, Time Factors, Randomized Controlled Trials as Topic, Clinical Trials, Phase III as Topic

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