Efficacy of Methylphenidate for Adults with Attention-Deficit Hyperactivity Disorder: A Meta-Regression Analysis

Castells, Xavier; Ramos-Quiroga, Josep Antoni; Rigau, David; Bosch, Rosa; Nogueira, Mariana; Vidal, Xavier; Casas, Miguel

doi:10.2165/11539440-000000000-00000

Cited by 197Attention Deficit Hyperactivity DisorderSchizophrenia research and treatmentSubstance Abuse Treatment and Outcomes

Efficacy of Methylphenidate for Adults with Attention-Deficit Hyperactivity Disorder: A Meta-Regression Analysis

Castells, Xavier, Ramos-Quiroga, Josep Antoni, Rigau, David, Bosch, Rosa, Nogueira, Mariana, Vidal, Xavier, Casas, Miguel·2011·CNS Drugs

DOI 10.2165/11539440-000000000-00000

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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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Psychostimulants including methylphenidate, dextroamphetamine, and mixed amphetamine salts are efficacious in the treatment of ADHD in children, adolescents, and adults.
“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]
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.
“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

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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)
ORCID: Bosch, Rosa
Vidal, Xavier
Casas, Miguel
Venue: CNS Drugs
Publisher: Springer Science and Business Media LLC
Published: 2011-02
Volume: 25
Issue: 2
Pages: 157-169
ISSN: 1172-7047 (ISSN-L)
DOI: 10.2165/11539440-000000000-00000
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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Efficacy of Methylphenidate for Adults with Attention-Deficit Hyperactivity Disorder: A Meta-Regression Analysis

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