The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Efficacy of Methylphenidate for Adults with Attention-Deficit Hyperactivity Disorder: A Meta-Regression Analysis
Abstract
Background The efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder (ADHD) shows wide between-study variability, which yields heterogeneous results in meta-analysis. The reasons for this variability have not been comprehensively investigated.Objectives To determine the influence of treatment-related covariates of methylphenidate for adults with ADHD by means of meta-analysis. Clinical and methodological moderators and clinical trial reporting quality were also collected to control for their potential confounding effect.Methods We searched for randomized, placebo-controlled clinical trials investigating the efficacy of methylphenidate for adults with ADHD. The study outcome was the efficacy of methylphenidate for reducing ADHD symptom severity. Treatment-related covariates included dose, type of drug-release formulation (formulations with a continuous drug release vs those with a non-continuous drug release), dose regimen (fixed vs flexible) and treatment length. Clinical (presence of co-morbid substance use disorders [SUD]) and methodological (design and rater) covariates were also collected, in addition to clinical trial reporting quality. The standardized mean difference (SMD) was calculated for each study. The analysis of the influence of methylphenidate effect modifiers was performed by means of random-effects meta-regression.Results Eighteen studies were included. Dose, type of formulation and SUD appeared to modify the efficacy of methylphenidate in the bivariate analysis. These variables were included in a multivariate meta-regression, which showed that methylphenidate, at an average dose of 57.4 mg/day, delivered by means of non-continuous-release formulations, had a moderate effect on ADHD symptoms compared with placebo (SMD 0.57-0.58). A dose-response relationship was found, indicating that efficacy could be increased by SMD 0.11-0.12 for every 10 mg increment of methylphenidate. Continuous-release formulations and co-morbid SUD appeared to reduce the efficacy of methylphenidate. Nevertheless, the effect of treatment formulation may have been confounded by co-morbid SUD, since all studies using this continuous-release formulation were conducted in dual ADHD-SUD patients. No residual heterogeneity was found.Conclusions This study shows that methylphenidate improves ADHD symptoms in adults in a dose-dependent fashion. The efficacy of methylphenidate appears to be reduced in patients with co-morbid SUD. It is unclear whether methylphenidate efficacy is influenced by the type of formulation, because the effect of this covariate is confounded by that of co-morbid SUD.
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In the citing paper
“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”
From Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD (2014) · cites this paper as [11]
In the citing paper
“The clinical effectiveness of stimulants such as methylphenidate in the treatment of ADHD suggests a putative role for both dopamine and noradrenaline in the manifestation of the disorder (Castells et al., 2011).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Castells et al., 2011
Citations
Cites
Assessing the quality of reports of randomized clinical trials: Is blinding necessary?
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Systematic Reviews in Health Care : Meta-Analysis in Context
Egger, M., Smith, G. D., & Altman, D. G. (2000) · Cited by 2,312
Meta-analyses involving cross-over trials: methodological issues
Elbourne, D. R., Altman, D. G., Higgins, J. P., Curtin, F., Worthington, H. V., & Vail, A. (2002) · International Journal of Epidemiology · doi:10.1093/ije/31.1.140 · Cited by 2,305
Pliszka, S. (2007) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e318054e724 · Cited by 1,765
Systematic Review: Why sources of heterogeneity in meta-analysis should be investigated
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ATTENTION-DEFICIT HYPERACTIVITY DISORDER IN ADULTS
Wender, P. H. (1998) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70039-3 · Cited by 728
Solanto, M. V. (1998) · Behavioural Brain Research · doi:10.1016/s0166-4328(97)00175-7 · Cited by 677
3-year follow-up of the NIMH MTA study
JENSEN, P. S., ARNOLD, L. E., SWANSON, J. M., VITIELLO, B., ABIKOFF, H. B., GREENHILL, L. L., HECHTMAN, L., HINSHAW, S. P., PELHAM, W. E., WELLS, K. C., et al. (2007) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e3180686d48 · Cited by 643
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- Faraone, 2006, Med Gen Med, 8, 4
Cited by
Sorted by citations
Basics of meta‐analysis: I 2 is not an absolute measure of heterogeneity
Borenstein, M., Higgins, J. P. T., Hedges, L. V., & Rothstein, H. R. (2017) · Research Synthesis Methods · doi:10.1002/jrsm.1230 · Cited by 1,848
“We will use the attention-deficit hyperactivity disorder (ADHD) analysis (Castells et al., 2011) as a motivating example.”
MethodAttention-deficit hyperactivity disorder
Posner, J., Polanczyk, G. V., & Sonuga-Barke, E. (2020) · The Lancet · doi:10.1016/s0140-6736(19)33004-1 · Cited by 835
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
“A 2011 meta-analysis [225] revealed that MPH (mean dose 41.”
Self-citationLive fast, die young? A review on the developmental trajectories of ADHD across the lifespan
Franke, B., Michelini, G., Asherson, P., Banaschewski, T., Bilbow, A., Buitelaar, J. K., Cormand, B., Faraone, S. V., Ginsberg, Y., Haavik, J., et al. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.08.001 · Cited by 643
“more recent estimates of persistence into young adulthood for children and adolescents diagnosed with DSM-IV combined type ADHD in Europe are much higher (up to 80%) ( Cheung et al., 2015a; van Lieshout et al., 2016b ), perhaps reflecting the severity of cases included in these studies, and/or the use of informant- ra…”
InfluentialSelf-citationvan Emmerik-van Oortmerssen, K., van de Glind, G., van den Brink, W., Smit, F., Crunelle, C. L., Swets, M., & Schoevers, R. A. (2012) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2011.12.007 · Cited by 535
“…treatment of ADHD with methylphenidate or atomoxetine is not as effective in ADHD patients with SUD compared to those without this comorbidity (Carpentier et al., 2005; Levin et al., 2006, 2007; Konstenius et al., 2010; Castells et al., 2011; Wilens et al., 2008a,b; Thurstone et al., 2010).”
Background
Metadata
- Authors
- Castells, X., Ramos-Quiroga, J. A., Rigau, D., Bosch, R., Nogueira, M., Vidal, X., & Casas, M.
- Affiliations
- Vall d'Hebron Hospital Universitari (ES)
- Universitat Autònoma de Barcelona (ES)
- Venue
- CNS Drugs
- Published
- 2011-02
- Volume
- 25
- Issue
- 2
- Pages
- 157-169
- ISSN
- 1172-7047 (ISSN-L)
- OpenAlex
- W2330451900
- Semantic Scholar
- 10b8118ac40b4e13bd9ab65989f9149be93a6f39
- Cited by
- 197
- References
- 62
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 10 · 2022: 14 · 2021: 14 · 2020: 16 · 2019: 11 · 2018: 15 · 2017: 21 · 2016: 15 · 2015: 15 · 2014: 20 · 2013: 17 · 2012: 14
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Departament de Salut, Generalitat de Catalunya
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- methylphenidate, adult ADHD, dose-response relationship, substance use disorders, ADHD symptom severity, effect modifiers, meta-regression, trial reporting quality, treatment duration, dosing regimen, confounding by comorbidity, standardized mean difference
- MeSH terms
- Adult, Attention Deficit Disorder with Hyperactivity, Delayed-Action Preparations, Dose-Response Relationship, Drug, Humans, Methylphenidate, Regression Analysis, Comorbidity, Randomized Controlled Trials as Topic, Treatment Outcome, Substance-Related Disorders, Diagnostic and Statistical Manual of Mental Disorders
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