A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients
Abstract
The lack of head-to-head clinical studies powered to compare atomoxetine and osmotic release oral system (OROS) methylphenidate necessitates treatment comparison by methods that include indirect evidence such as network meta-analysis (NMA). A NMA assessing the relative treatment effects of atomoxetine and OROS methylphenidate in adults with attention-deficit/hyperactivity disorder (ADHD) was conducted. Studies were identified by systematic literature review. Analyses summarised improvements in efficacy, measured by ADHD-specific scales, using Cohen'sdto calculate the standardised mean difference (SMD), and all cause discontinuations. Results showed effect sizes (SMD, 95% credible interval (CrI)) relative to placebo that did not differ significantly between atomoxetine (0.46, 0.36-0.56) and OROS methylphenidate (0.51, 0.40-0.63) in clinical studies of up to 12 weeks' duration (SMD, 95% CrI for atomoxetine versus OROS methylphenidate: -0.05, -0.18-0.08). Patients treated with these medications responded better than those given placebo across all analyses. There was also no significant difference in discontinuation rates between atomoxetine and OROS methylphenidate (odds ratio, 95% CrI: 0.85, 0.53-1.35). Between-study heterogeneity was low overall. Results of this NMA suggest that the efficacy of atomoxetine and OROS methylphenidate in adults does not differ significantly. Clinical guidelines may require amendment to reflect these recent data.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous network meta-analyses in ADHD have focused on either children and adolescents or adults only, have typically compared only a few drugs, or have addressed exclusively the safety of treatments.
“Previous network meta-analyses in ADHD have focused on either children and adolescents19, 20, 21, 22, 23, 24 or adults only,25, 26, 27, 28 have typically compared only a few drugs,24, 25, 27, 29 or have addressed exclusively the safety of treatments.26”
Cites
KESSLER, R. C., ADLER, L., AMES, M., DEMLER, O., FARAONE, S., HIRIPI, E., HOWES, M. J., JIN, R., SECNIK, K., SPENCER, T., et al. (2005) · Psychological Medicine · doi:10.1017/s0033291704002892 · Cited by 3,452 · see citing works
Leucht, S., Cipriani, A., Spineli, L., Mavridis, D., Örey, D., Richter, F., Samara, M., Barbui, C., Engel, R. R., Geddes, J. R., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60733-3 · Cited by 2,561 · see citing works
Molecular genetics of attention-deficit/hyperactivity disorder
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., & Sklar, P. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.024 · Cited by 2,357 · see citing works
Metan: fixed- and random-effects meta-analysis
Harris, R. J., Deeks, J. J., Altman, D. G., Bradburn, M. J., Harbord, R. M., & Sterne, J. A. C. (2008) · The Stata Journal: Promoting communications on statistics and Stata · doi:10.1177/1536867x0800800102 · Cited by 1,027 · see citing works
Kooij, S. J., Bejerot, S., Blackwell, A., Caci, H., Casas-Brugué, M., Carpentier, P. J., Edvinsson, D., Fayyad, J., Foeken, K., Fitzgerald, M., et al. (2010) · BMC Psychiatry · doi:10.1186/1471-244x-10-67 · Cited by 928 · cited 4× · see citing works
“Older guidelines such as National Institute for Health and Clinical Excellence (NICE) guidelines (NICE, 2008) and European consensus (Kooij et al., 2010) guidelines recommend methylphenidate as first-line treatment for adults with ADHD, although they acknowledge the lack of head-to-head clinical…”
BackgroundInfluentialMolecular Genetics of Attention Deficit Hyperactivity Disorder
Faraone, S. V., & Mick, E. (2010) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2009.12.004 · Cited by 411 · see citing works
Faraone, S. V., & Glatt, S. J. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.08m04902pur · Cited by 387 · see citing works
Jansen, J. P., Trikalinos, T., Cappelleri, J. C., Daw, J., Andes, S., Eldessouki, R., & Salanti, G. (2014) · Value in Health · doi:10.1016/j.jval.2014.01.004 · Cited by 319 · see citing works
Biederman, J., Mick, E., Surman, C., Doyle, R., Hammerness, P., Harpold, T., Dunkel, S., Dougherty, M., Aleardi, M., & Spencer, T. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.011 · Cited by 267 · see citing works
Castells, X., Ramos-Quiroga, J. A., Rigau, D., Bosch, R., Nogueira, M., Vidal, X., & Casas, M. (2011) · CNS Drugs · doi:10.2165/11539440-000000000-00000 · Cited by 197 · see citing works
Medori, R., Ramos-Quiroga, J. A., Casas, M., Kooij, J. J. S., Niemelä, A., Trott, G.-E., Lee, E., & Buitelaar, J. K. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.11.008 · Cited by 186 · see citing works
Adler, L. A., Liebowitz, M., Kronenberger, W., Qiao, M., Rubin, R., Hollandbeck, M., Deldar, A., Schuh, K., & Durell, T. (2009) · Depression and Anxiety · doi:10.1002/da.20549 · Cited by 176 · see citing works
Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders
Wilens, T. E., Adler, L. A., Weiss, M. D., Michelson, D., Ramsey, J. L., Moore, R. J., Renard, D., Brady, K. T., Trzepacz, P. T., Schuh, L. M., et al. (2008) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2008.02.009 · Cited by 171 · see citing works
on behalf of the study group, Rösler, M., Fischer, R., Ammer, R., Ose, C., & Retz, W. (2009) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-008-0845-4 · Cited by 155 · see citing works
Koesters, M., Becker, T., Kilian, R., Fegert, J., & Weinmann, S. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881108092338 · Cited by 142 · see citing works
Cunill, R., Castells, X., Tobias, A., & Capellà, D. (2013) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.3473 · Cited by 70 · see citing works
Durell, T. M., Adler, L. A., Williams, D. W., Deldar, A., McGough, J. J., Glaser, P. E., Rubin, R. L., Pigott, T. A., Sarkis, E. H., & Fox, B. K. (2013) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31827d8a23 · Cited by 64 · see citing works
Roskell, N. S., Setyawan, J., Zimovetz, E. A., & Hodgkins, P. (2014) · Current Medical Research and Opinion · doi:10.1185/03007995.2014.904772 · Cited by 42 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cortese, S., Adamo, N., Del Giovane, C., Mohr-Jensen, C., Hayes, A. J., Carucci, S., Atkinson, L. Z., Tessari, L., Banaschewski, T., Coghill, D., et al. (2018) · The Lancet Psychiatry · doi:10.1016/s2215-0366(18)30269-4 · Cited by 1,402 · see citing works
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 · see citing works
“studies providing robust comparative analysis of efficacy differences [221].”
BackgroundPharmacological and non-pharmacological treatment of adults with ADHD: A meta-review
De Crescenzo, F., Cortese, S., Adamo, N., & Janiri, L. (2017) · Evidence Based Mental Health · doi:10.1136/eb-2016-102415 · Cited by 150 · see citing works
“63).(16) Methylphenidate, regardless of the type of formulation, has also been found to be significantly more efficacious than placebo in reducing executive dysfunctions that are often associated with ADHD (response inhibition: SMD 0.”
BackgroundResultInfluentialElliott, J., Johnston, A., Husereau, D., Kelly, S., Eagles, C., Charach, A., Hsieh, S., Bai, Z., Hossain, A., Skidmore, B., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0240584 · Cited by 93 · see citing works
Zhu, Y., Evans, E., Mooney, L. J., Saxon, A. J., Kelleghan, A., Yoo, C. K., & Hser, Y. (2018) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-018-9801-x · Cited by 71 · see citing works
Effects of cannabinoid administration for pain: A meta-analysis and meta-regression.
Yanes, J. A., McKinnell, Z. E., Reid, M. A., Busler, J. N., Michel, J. S., Pangelinan, M. M., Sutherland, M. T., Younger, J., González, R., & Robinson, J. L. (2019) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000281 · Cited by 67 · see citing works
“Regarding pharmacologic manipulations, pooled effect sizes are used to characterize cross-study drug administration effects on specific end-points (Wilkinson et al., 2018), or to make comparisons between two (or more) drug administration conditions (Bushe et al., 2016).”
BackgroundClemow, D. B., Bushe, C., Mancini, M., Ossipov, M. H., & Upadhyaya, H. P. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s115707 · Cited by 59 · see citing works
“28,39,40 42 Data from recent longer-term studies that incorporate current ADHD trial design concepts also show that there is equivalent efficacy for atomoxetine and methylphenidate, both in adults and children, 43,44 including data from the most recent updated network meta-analysis.”
Self-citationTemperament correlates in adult ADHD: A systematic review★★
Pinzone, V., Rossi, P. D., Trabucchi, G., Lester, D., Girardi, P., & Pompili, M. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.04.006 · Cited by 40 · see citing works
Pievsky, M. A., & McGrath, R. E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.05.012 · Cited by 43 · see citing works
Cortese, S., Adamo, N., Jensen, C. M., Hayes, A. J., Bhatti, S., Carucci, S., Giovane, C. D., Atkinson, L. Z., Banaschewski, T., Simonoff, E. A., et al. (2017) · BMJ Open · doi:10.1136/bmjopen-2016-013967 · Cited by 45 · see citing works
Liu, Q., Zhang, H., Fang, Q., & Qin, L. (2017) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2016.1273320 · Cited by 24 · see citing works
“Then, several meta-analyses have compared the efficiency of MPH and ATX (C. Bushe et al., 2016; C. J. Bushe & Savill, 2013; Hanwella, Senanayake, & de Silva, 2011; Hazell et al., 2011).”
BackgroundResultInfluentialLow, A.-M., le Sommer, J., Vangkilde, S., Fagerlund, B., Glenthoj, B. Y., Sonuga-Barke, E. J. S., Habekost, T., & Jepsen, J. R. M. (2018) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyy070 · Cited by 20 · see citing works
“Methylphenidate, a dopamine reuptake inhibitor, is recommended as a first line treatment for adult ADHD (Bushe et al., 2016).”
BackgroundLow, A.-M., Vangkilde, S., le Sommer, J., Fagerlund, B., Glenthoj, B. Y., Jepsen, J. R. M., Bundesen, C., Petersen, A., & Habekost, T. (2018) · Psychological Medicine · doi:10.1017/s0033291718003628 · Cited by 33 · see citing works
“Methylphenidate is recommended as the first-line treatment for ADHD in international guidelines, and reduces symptoms of ADHD in adults effectively (Bushe et al., 2016).”
BackgroundSafety of Treatments for ADHD in Adults: Pairwise and Network Meta-Analyses
Chierrito de Oliveira, D., Guerrero de Sousa, P., Borges dos Reis, C., Tonin, F. S., Maria Steimbach, L., Virtuoso, S., Fernandez-Llimos, F., Pontarolo, R., & Cristina Conegero Sanches, A. (2019) · Journal of Attention Disorders · doi:10.1177/1087054717696773 · Cited by 14 · see citing works
Current nonstimulant medications for adults with attention-deficit/hyperactivity disorder
Brancati, G. E., Magnesa, A., Acierno, D., Carli, M., Rosa, U. D., Froli, A., Gemignani, S., Ventura, L., Weiss, F., & Perugi, G. (2024) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2024.2370346 · Cited by 13 · see citing works
“In addition, a network meta-analysis comparing ATX and OROS MPH revealed comparable effect sizes relative to placebo for both medications, with no significant differences in terms of efficacy and discontinuation rates [34].”
Shim, S.-H., Woo, Y., Kim, J. S., Heo, I. S., Yoon, H.-J., Sung, H., Lee, J., & Bahk, W. (2022) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2022.20.1.143 · Cited by 9 · see citing works
“Moreover, the efficacy of ATX and OROS MPH in adults did not differ significantly [37].”
BackgroundImmediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults
Cândido, R. C. F., de Padua, C. A. M., Golder, S., & Junqueira, D. R. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013011.pub2 · Cited by 33 · see citing works
“[DOI: 10.1176/ ajp.94.3.577] Bushe 2016 Bushe C, Day K, Reed V, Karlsdotter K, Berggren L, Pitcher A, et al. A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients.”
BackgroundInfluentialBrancati, G. E., Dominicis, F. D., Petrucci, A., Pallucchini, A., Carli, M., Medda, P., Schiavi, E., Rossi, P. D., Vicari, S., & Perugi, G. (2023) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2023.2168750 · Cited by 5 · see citing works
Low, A.-M., Vangkilde, S., le Sommer, J., Fagerlund, B., Glenthoj, B. Y., Jepsen, J. R. M., & Habekost, T. (2022) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2022.2080253 · Cited by 7 · see citing works
“Methylphenidate is recommended as the first line treatment for adult ADHD patients in national and international guidelines [7,8].”
BackgroundAlopecia reversible secundaria a metilfenidato OROS
Núñez-Garces, M., Sánchez-Gayango, A., & Romero-Pérez, C. (2020) · doi:10.1016/j.rcp.2018.09.003 · Cited by 5
Crescenzo, F. D., Зиганшина, Л. Е., Yudina, E. V., Kaplan, Y. C., Ciabattini, M., Wei, Y., & Hoyle, C. H. V. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013044 · Cited by 6 · see citing works
Eto, A., Endo, A., Yoshida, T., Seki, Y., Taguchi, K., Hongo, M., Takahashi, K., Shiko, Y., Hirano, Y., & Shimizu, E. (2025) · Psychotherapy and Psychosomatics · doi:10.1159/000546539 · Cited by 6 · see citing works
“Similarly, atomoxetine showed an average improvement of − 15.3, which was signi fi cantly greater than that of the placebo group [45].”
InfluentialSchein, J. R., Cloutier, M., Gauthier‐Loiselle, M., Catillon, M., Xu, C., Qu, A., Lee, F., & Childress, A. C. (2024) · Journal of Comparative Effectiveness Research · doi:10.57264/cer-2024-0089 · Cited by 6 · see citing works
To Prescribe or Not? Pharmacological Options in Adult Attention-Deficit/Hyperactivity Disorder
Aoshima-Kilroy, A., Banu, S., Udoetuk, S., Shah, A. A., & Moukaddam, N. (2017) · Psychiatric Annals · doi:10.3928/00485713-20170510-01 · Cited by 1 · see citing works
Nurkhametova, D., Yudina, E. V., Wei, Y., Abakumova, T. R., & Зиганшина, Л. Е. (2026) · International Journal of Risk & Safety in Medicine · doi:10.1177/09246479261461033
Why not try a non-stimulant to treat ADHD?
Kripalani, M. (2023) · Annals of Pharmacology and Pharmaceutical Sciences · doi:10.52338/apps.2023.1023
Reversible alopecia secondary to OROS methylphenidate
Núñez-Garces, M., Sánchez-Gayango, A., & Romero-Pérez, C. (2020) · doi:10.1016/j.rcpeng.2018.09.003
- Authors
- Bushe, C., Day, K., Reed, V., Karlsdotter, K., Berggren, L., Pitcher, A., Televantou, F., & Haynes, V.
- Affiliations
- Eli Lilly, Windlesham, UK
- Eli Lilly (United States) (US)
- Eli Lilly (Germany) (DE)
- IQVIA (United States) (US)
- Corresponding author
- Bushe, Chris
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2016-03-22
- Volume
- 30
- Issue
- 5
- Pages
- 444-458
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2320331035
- Cited by
- 31
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 8 · 2017: 5 · 2016: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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
- atomoxetine, attention deficit hyperactivity disorder, adult ADHD, stimulant medication, drug efficacy comparison, treatment discontinuation, placebo response
- MeSH terms
- Atomoxetine Hydrochloride, Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Humans, Methylphenidate, Adrenergic Uptake Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
