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Currently, there is no solid evidence\u2010base for pharmacotherapy to improve cognitive functioning after ABI, nevertheless off\u2010label use is widely applied in clinical practice. This meta\u2010analysis and meta\u2010regression aims to quantitatively aggregate the available evidence for the effects of pharmacological agents used in the treatment of cognitive impairments following ABI. We conducted a comprehensive search of Embase, Medline Ovid, and Cochrane Controlled Trials Register databases for randomized controlled and crossover trials. Meta\u2010analytic effects were calculated for each pharmaceutical agent and targeted neuromodulator system. Cognitive outcome measures were aggregated across cognitive domains. Of 8,216 articles, 41 studies (4,434 patients) were included. The noradrenergic agent methylphenidate showed a small, significant positive effect on cognitive functioning in patients with traumatic brain injury (TBI;\n                    <jats:italic>k<\/jats:italic>\n                    \u2009=\u200914,\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u20090.34, 95% confidence interval: 0.12\u20130.56,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.003). Specifically, methylphenidate was found to improve cognitive functions related to executive memory, baseline speed, inhibitory control, and variability in responding. The cholinergic drug donepezil demonstrated a large effect size, albeit based on a limited number of studies (\n                    <jats:italic>k<\/jats:italic>\n                    \u2009=\u20093,\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u20091.68,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.03). No significant effects were observed for other agents. Additionally, meta\u2010regression analysis did not identify significant sources of heterogeneity in treatment response. Our meta\u2010analysis supports the use of methylphenidate for enhancing cognitive functioning in patients with TBI. Although donepezil shows potential, it warrants further research. These results could guide clinical decision making, inform practice guidelines, and direct future pharmacotherapeutic research in ABI.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3186","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T08:34:48Z","timestamp":1706690088000},"page":"971-987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacotherapy to Improve Cognitive Functioning After Acquired Brain Injury: A\u00a0Meta\u2010Analysis and Meta\u2010Regression"],"prefix":"10.1002","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2489-0947","authenticated-orcid":false,"given":"Ruud","family":"van der Veen","sequence":"first","affiliation":[{"name":"Follow Me Program &amp; Emma Neuroscience Group, Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam Amsterdam Reproduction and Development Research Institute  Amsterdam The Netherlands"},{"name":"Daan Theeuwes Center for Intensive Neurorehabilitation  Woerden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0200-0445","authenticated-orcid":false,"given":"Marsh","family":"K\u00f6nigs","sequence":"additional","affiliation":[{"name":"Follow Me Program &amp; Emma Neuroscience Group, Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam Amsterdam Reproduction and Development Research Institute  Amsterdam The Netherlands"},{"name":"Daan Theeuwes Center for Intensive Neurorehabilitation  Woerden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Bakker","sequence":"additional","affiliation":[{"name":"Reade, Amsterdam Rehabilitation Research Centre  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andries","family":"van Iperen","sequence":"additional","affiliation":[{"name":"Daan Theeuwes Center for Intensive Neurorehabilitation  Woerden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-3210","authenticated-orcid":false,"given":"Saskia","family":"Peerdeman","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6735-7379","authenticated-orcid":false,"given":"Pierre M.","family":"Bet","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0218-5630","authenticated-orcid":false,"given":"Jaap","family":"Oosterlaan","sequence":"additional","affiliation":[{"name":"Follow Me Program &amp; Emma Neuroscience Group, Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam Amsterdam Reproduction and Development Research Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2011.07.023"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3171\/2017.10.JNS17352"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00120"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005327"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-018791"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/09638288.2019.1613682"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/09602011.2015.1113996"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2013.11.004"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-015-0288-2"},{"key":"e_1_2_10_10_1","article-title":"Multi\u2010disciplinary rehabilitation for acquired brain injury in adults of working age","volume":"2015","author":"Turner\u2010Stokes L.","year":"2015","journal-title":"Cochrane Database Syst. 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