Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis - PubMed (original) (raw)
Meta-Analysis
Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis
Xavier Castells et al. CNS Drugs. 2011 Feb.
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.
Similar articles
- Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.
Epstein T, Patsopoulos NA, Weiser M. Epstein T, et al. Cochrane Database Syst Rev. 2014 Sep 18;(9):CD005041. doi: 10.1002/14651858.CD005041.pub2. Cochrane Database Syst Rev. 2014. PMID: 25230710 Updated. Review. - Randomized, Double-Blind, Placebo-Controlled Acute Comparator Trials of Lisdexamfetamine and Extended-Release Methylphenidate in Adolescents With Attention-Deficit/Hyperactivity Disorder.
Newcorn JH, Nagy P, Childress AC, Frick G, Yan B, Pliszka S. Newcorn JH, et al. CNS Drugs. 2017 Nov;31(11):999-1014. doi: 10.1007/s40263-017-0468-2. CNS Drugs. 2017. PMID: 28980198 Free PMC article. - Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults.
Castells X, Blanco-Silvente L, Cunill R. Castells X, et al. Cochrane Database Syst Rev. 2018 Aug 9;8(8):CD007813. doi: 10.1002/14651858.CD007813.pub3. Cochrane Database Syst Rev. 2018. PMID: 30091808 Free PMC article. - Substance use disorders in association with attention-deficit/hyperactivity disorder, co-morbid mental disorders, and medication in a nationwide sample.
Steinhausen HC, Bisgaard C. Steinhausen HC, et al. Eur Neuropsychopharmacol. 2014 Feb;24(2):232-41. doi: 10.1016/j.euroneuro.2013.11.003. Epub 2013 Nov 18. Eur Neuropsychopharmacol. 2014. PMID: 24314850 - Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder and Substance Use Disorders.
Simon N, Rolland B, Karila L. Simon N, et al. Curr Pharm Des. 2015;21(23):3359-66. doi: 10.2174/1381612821666150619093254. Curr Pharm Des. 2015. PMID: 26088112 Review.
Cited by
- From attention-deficit hyperactivity disorder to sporadic Alzheimer's disease-Wnt/mTOR pathways hypothesis.
Grünblatt E, Homolak J, Babic Perhoc A, Davor V, Knezovic A, Osmanovic Barilar J, Riederer P, Walitza S, Tackenberg C, Salkovic-Petrisic M. Grünblatt E, et al. Front Neurosci. 2023 Feb 16;17:1104985. doi: 10.3389/fnins.2023.1104985. eCollection 2023. Front Neurosci. 2023. PMID: 36875654 Free PMC article. - Developmental nicotine exposure precipitates multigenerational maternal transmission of nicotine preference and ADHD-like behavioral, rhythmometric, neuropharmacological, and epigenetic anomalies in adolescent mice.
Buck JM, Sanders KN, Wageman CR, Knopik VS, Stitzel JA, O'Neill HC. Buck JM, et al. Neuropharmacology. 2019 May 1;149:66-82. doi: 10.1016/j.neuropharm.2019.02.006. Epub 2019 Feb 8. Neuropharmacology. 2019. PMID: 30742847 Free PMC article. - Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer's Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients.
Blanco-Silvente L, Castells X, Saez M, Barceló MA, Garre-Olmo J, Vilalta-Franch J, Capellà D. Blanco-Silvente L, et al. Int J Neuropsychopharmacol. 2017 Jul 1;20(7):519-528. doi: 10.1093/ijnp/pyx012. Int J Neuropsychopharmacol. 2017. PMID: 28201726 Free PMC article. Review. - Effects of Methylphenidate on the Dopamine Transporter and Beyond.
Zetterström TSC, Quansah E, Grootveld M. Zetterström TSC, et al. Curr Top Behav Neurosci. 2022;57:127-157. doi: 10.1007/7854_2022_333. Curr Top Behav Neurosci. 2022. PMID: 35507284 - The South African Society of Psychiatrists/Psychiatry Management Group management guidelines for adult attention-deficit/hyperactivity disorder.
Schoeman R, Liebenberg R. Schoeman R, et al. S Afr J Psychiatr. 2017 Apr 25;23:1060. doi: 10.4102/sajpsychiatry.v23i0.1060. eCollection 2017. S Afr J Psychiatr. 2017. PMID: 30263194 Free PMC article.
References
- J Clin Pharmacol. 2000 Apr;40(4):379-88 - PubMed
- Clin Neuropharmacol. 1985;8(4):343-56 - PubMed
- Psychopharmacology (Berl). 2008 Mar;197(1):1-11 - PubMed
- J Atten Disord. 2002 Sep;6(2):49-60 - PubMed
- Clin Pharmacol Ther. 1999 Sep;66(3):295-305 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical