Efficacy, Acceptability, and Tolerability of Lisdexamfetamine, Mixed Amphetamine Salts, Methylphenidate, and Modafinil in the Treatment of Attention-Deficit Hyperactivity Disorder in Adults: A Systematic Review and Meta-analysis
Abstract
Objective Psychostimulants are the first-line treatment in adults with attention-deficit hyperactivity disorder (ADHD). This meta-analysis aimed to evaluate the efficacy, acceptability, and tolerability of lisdexamfetamine (LDX), mixed amphetamine salts (MASs), modafinil (MDF), and methylphenidate (MPH) in comparison with placebo. Data sources We systematically searched PubMed/MEDLINE and Clinicaltrials.gov in May 2016, along with CENTRAL and EU Clinical Trials Register in February 2016, for the randomized, double-blind, placebo-controlled, parallel-group clinical trials conducted on adults diagnosed with ADHD. Study selection and data extraction Substantial comorbidity, substance abuse or dependence, and nonpharmacological interventions represented grounds for exclusion. Published reports were the sole source for data extraction. Improvement in ADHD symptoms was the primary outcome. Random-effects model meta-analysis was applied to calculate the standardized mean difference (SMD) with 95% CIs. Data synthesis The search retrieved 701 records, of which 20 studies were eligible for analysis. High effect size (expressed as SMD) in reducing ADHD symptoms was observed for LDX (-0.89; 95% CI = -1.09, -0.70), whereas MASs (-0.64; 95% CI = -0.83, -0.45) and MPH (-0.50; 95% CI = -0.58, -0.41) reduced symptoms moderately compared with placebo. No efficacy was shown for MDF (0.08; 95% CI; -0.18, 0.34). Relevance to Patient Care and Clinical Practice: In this meta-analysis, the efficacy,…
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Lisdexamfetamine reduces ADHD symptoms with large effect sizes in children and adults.
“Meta-analyses have shown efficacy of lisdexamfetamine in improving ADHD symptoms with large effect sizes (32, 33).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [33]
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Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD
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“78).(18) This meta-analysis includes new studies with LDX for treatment of ADHD in adults.”
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El Masri, S., Kowalczyk, O. S., Chiu, T. H., Criaud, M., Lukito, S., Mazibuko, N., Salazar de Pablo, G., Perez Rodriguez, V., Makos, O., Lam, S.-L., et al. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1676472
- Authors
- Stuhec, M., Lukić, P., & Locatelli, I.
- Affiliations
- Ormoz Psychiatric Hospital, Department of clinical pharmacy, Ormoz, Slovenia, European Union
- University of Ljubljana (SI)
- ORCID
- Locatelli, Igor
- Venue
- Annals of Pharmacotherapy
- Publisher
- SAGE Publications
- Published
- 2018-08-17
- Volume
- 53
- Issue
- 2
- Pages
- 121-133
- ISSN
- 0012-6578 (ISSN-L)
- 1060-0280
- 1542-6270
- OpenAlex
- W2886241630
- Cited by
- 46
- References
- 13
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 12 · 2022: 10 · 2021: 6 · 2020: 5 · 2018: 1
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroethics, Human Enhancement, Biomedical Innovations
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- adult ADHD, lisdexamfetamine, mixed amphetamine salts, methylphenidate, modafinil, psychostimulants, ADHD symptom reduction, treatment efficacy, tolerability, acceptability, placebo comparison
- MeSH terms
- Lisdexamfetamine Dimesylate, Modafinil, Adult, Amphetamine, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Double-Blind Method, Humans, Methylphenidate, Salts, Treatment Outcome
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