Differences in outcomes following an intensive upper-limb rehabilitation program for patients with common central nervous system-acting drug prescriptions
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Abstract
Background: Difficulty using the upper-limb is a major barrier to independence for many patients post-stroke or brain injury. High dose rehabilitation can result in clinically significant improvements in function even years after the incident; however, there is still high variability in patient responsiveness to such interventions that cannot be explained by age, sex, or time since stroke. Methods: This retrospective study investigated whether patients prescribed certain classes of central nervous system-acting drugs—γ-aminobutyric acid (GABA) agonists, antiepileptics, and antidepressants—differed in their outcomes on the three-week intensive Queen Square Upper-Limb program. For 277 stroke or brain injury patients (167 male, median age 52 years (IQR: 21), median time since incident 20 months (IQR: 26)) upper-limb impairment and activity was assessed at admission to the program and at six months post-discharge, using the upper limb component of the Fugl-Meyer, Action Research Arm Test, and Chedoke Arm and Hand Activity Inventory. Drug prescriptions were obtained from primary care physicians at referral. Specification curve analysis was used to protect against selective reporting results and add robustness to the conclusions of this retrospective study. Results: Patients with GABA agonist prescriptions had significantly worse upper-limb scores at admission but no evidence for a significant difference in program-induced improvements was found. Additionally, no evidence of significant differences in patients with or without antiepileptic drug prescriptions on either admission to, or improvement on, the program was found in this study. Although no evidence was found for differences in admission scores, patients with antidepressant prescriptions experienced reduced improvement in upper-limb function, even when accounting for anxiety and depression scores. Conclusions: These results demonstrate that, when prescribed typically, there was no evidence that patients prescribed GABA agonists performed worse on this high-intensity rehabilitation program. Patients prescribed antidepressants, however, performed poorer than expected on the Queen Square Upper-Limb rehabilitation program. While the reasons for these differences are unclear, identifying these patients prior to admission may allow for better accommodation of differences in their rehabilitation needs.
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Cites
Feigin, V. L., Forouzanfar, M. H., Krishnamurthi, R., Mensah, G. A., Connor, M., Bennett, D. A., Moran, A. E., Sacco, R. L., Anderson, L., Truelsen, T., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61953-4 · Cited by 3,899 · see citing works
The association between adolescent well-being and digital technology use
Orben, A., & Przybylski, A. K. (2019) · Nature Human Behaviour · doi:10.1038/s41562-018-0506-1 · Cited by 1,500 · see citing works
Hackett, M. L., & Pickles, K. (2014) · International Journal of Stroke · doi:10.1111/ijs.12357 · Cited by 1,140 · see citing works
Ayerbe, L., Ayis, S., Wolfe, C. D. A., & Rudd, A. G. (2013) · British Journal of Psychiatry · doi:10.1192/bjp.bp.111.107664 · Cited by 980 · see citing works
Chollet, F., Tardy, J., Albucher, J.-F., Thalamas, C., Berard, E., Lamy, C., Bejot, Y., Deltour, S., Jaillard, A., Niclot, P., et al. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70314-8 · Cited by 925 · see citing works
The antidepressant fluoxetine restores plasticity in the adult visual cortex
Vetencourt, J. F. M., Sale, A., Viegi, A., Baroncelli, L., De Pasquale, R., F. O'Leary, O., Castrén, E., & Maffei, L. (2008) · Science · doi:10.1126/science.1150516 · Cited by 890 · see citing works
Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke
Clarkson, A. N., Huang, B. S., MacIsaac, S. E., Mody, I., & Carmichael, S. T. (2010) · Nature · doi:10.1038/nature09511 · Cited by 869 · see citing works
The hospital anxiety and depression scale
Stern, A. F. (2014) · Occupational Medicine · doi:10.1093/occmed/kqu024 · Cited by 728 · see citing works
Page, S. J., Fulk, G. D., & Boyne, P. (2012) · Physical Therapy · doi:10.2522/ptj.20110009 · Cited by 705 · see citing works
The long-term outcome of arm function after stroke: results of a follow-up study
Broeks, J., Lankhorst, G. J., RUMPING, K., & Prevo, A. J. H. (1999) · Disability and Rehabilitation · doi:10.1080/096382899297459 · Cited by 694 · see citing works
Getting Neurorehabilitation Right: What Can Be Learned From Animal Models?
Krakauer, J. W., Carmichael, S. T., Corbett, D., & Wittenberg, G. F. (2012) · Neurorehabilitation and Neural Repair · doi:10.1177/1545968312440745 · Cited by 591 · see citing works
van der Lee, J. H., de Groot, V., Beckerman, H., WAGENAAR, R. C., Lankhorst, G. J., & Bouter, L. M. (2001) · Archives of Physical Medicine and Rehabilitation · doi:10.1053/apmr.2001.18668 · Cited by 499 · see citing works
Social media’s enduring effect on adolescent life satisfaction
Orben, A., Dienlin, T., & Przybylski, A. K. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902058116 · Cited by 485 · see citing works
Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke
Pariente, J., Loubinoux, I., Carel, C., Albucher, J., Léger, A., MANELFE, C., Rascol, O., & Chollet, F. (2001) · Annals of Neurology · doi:10.1002/ana.1257 · Cited by 364 · see citing works
Dam, M., Tonin, P., Boni, A., Pizzolato, G., Casson, S., Ermani, M., Freo, U., Piron, L., & Battistin, L. (1996) · Stroke · doi:10.1161/01.str.27.7.1211 · Cited by 346 · see citing works
Intensive upper limb neurorehabilitation in chronic stroke: outcomes from the Queen Square programme
Ward, N., Brander, F., & Kelly, K. (2019) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2018-319954 · Cited by 345 · see citing works
Self-citationBütefisch, C. M., Weβling, M., Netz, J., Seitz, R. J., & Hömberg, V. (2007) · Neurorehabilitation and neural repair · doi:10.1177/1545968307301769 · Cited by 267 · see citing works
Recovery of function after brain damage: Severe and chronic disruption by diazepam
Schallert, T. J., Hernández, T. D., & Barth, T. M. (1986) · Brain Research · doi:10.1016/0006-8993(86)90261-1 · Cited by 258 · see citing works
Common drugs may influence motor recovery after stroke
Goldstein, L. B. (1995) · Neurology · doi:10.1212/wnl.45.5.865 · Cited by 235 · see citing works
Ipsilesional anodal tDCS enhances the functional benefits of rehabilitation in patients after stroke
Allman, C., Amadi, U., Winkler, A. M., Wilkins, L., Filippini, N., Kischka, U., Stagg, C. J., & Johansen‐Berg, H. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad5651 · Cited by 225 · see citing works
Specification Curve: Descriptive and Inferential Statistics on All Reasonable SpecificationsPreprint
Simonsohn, U., Simmons, J. P., & Nelson, L. D. (2015) · SSRN Electronic Journal · doi:10.2139/ssrn.2694998 · Cited by 199 · see citing works
Barreca, S. R., Stratford, P. W., Lambert, C. L., Masters, L. M., & Streiner, D. L. (2005) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2005.03.017 · Cited by 186 · see citing works
Potential Effects of Common Drugs on Stroke Recovery
Goldstein, L. B. (1998) · Archives of Neurology · doi:10.1001/archneur.55.4.454 · Cited by 184 · see citing works
Feyissa, A. M., Hasan, T. F., & Meschia, J. F. (2018) · European Journal of Neurology · doi:10.1111/ene.13813 · Cited by 182 · see citing works
Lundström, E., Isaksson, E., Näsman, P., Wester, P. O., Mårtensson, B., Norrving, B. G., Wallén, H., Borg, J., Dennis, M. S., Mead, G. E., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30219-2 · Cited by 157 · see citing works
Hankey, G. J., Hackett, M. L., Almeida, O. P., Flicker, L. A., Mead, G. E., Dennis, M. S., Etherton‐Beer, C., Ford, A. H., Billot, L., Jan, S., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30207-6 · Cited by 149 · see citing works
Probing Birth-Order Effects on Narrow Traits Using Specification-Curve Analysis
Rohrer, J. M., Egloff, B., & Schmukle, S. C. (2017) · Psychological Science · doi:10.1177/0956797617723726 · Cited by 146 · see citing works
Acler, M., Robol, E., Fiaschi, A., & Manganotti, P. (2009) · Journal of Neurology · doi:10.1007/s00415-009-5093-7 · Cited by 139 · see citing works
Blicher, J. U., Near, J., Næss‐Schmidt, E. T., Stagg, C. J., Johansen‐Berg, H., Nielsen, J. F., Østergaard, L., & Ho, Y.-C. L. (2014) · Neurorehabilitation and neural repair · doi:10.1177/1545968314543652 · Cited by 137 · see citing works
Citalopram Improves Dexterity in Chronic Stroke Patients
Zittel, S., Weiller, C., & Liepert, J. (2008) · Neurorehabilitation and neural repair · doi:10.1177/1545968307312173 · Cited by 127 · see citing works
Poststroke Motor Dysfunction and Spasticity
Hesse, S., & Werner, C. (2003) · CNS Drugs · doi:10.2165/00023210-200317150-00004 · Cited by 85 · see citing works
Ng, K., Gibson, E. M., Hubbard, R., Yang, J., Caffo, B. C., O’Brien, R., Krakauer, J. W., & Zeiler, S. R. (2015) · Stroke · doi:10.1161/strokeaha.115.010471 · Cited by 83 · see citing works
Kim, Y. K., Yang, E. J., Cho, K., Lim, J. Y., & Paik, N. (2014) · Neurorehabilitation and neural repair · doi:10.1177/1545968313520411 · Cited by 70 · see citing works
Fleming, M. K., Smejka, T., Slater, D. H., van Gils, V., Garratt, E., Kara, E. Y., & Johansen‐Berg, H. (2020) · Neurorehabilitation and neural repair · doi:10.1177/1545968320929669 · Cited by 64 · see citing works
Wang, Z.-F., Fessler, E. B., & Chuang, D. (2011) · Acta Pharmacologica Sinica · doi:10.1038/aps.2011.140 · Cited by 57 · see citing works
Investigating post-stroke fatigue: An individual participant data meta-analysis
Cumming, T. B., Yeo, A. B., Marquez, J. L., Churilov, L. P., Annoni, J., Badaru, U. M., Ghotbi, N., Harbison, J., Kwakkel, G., Lerdal, A., et al. (2018) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2018.08.006 · Cited by 57 · see citing works
Pushing the Rehabilitation Boundaries: Hand Motor Impairment Can Be Reduced in Chronic Stroke
Mawase, F., Cherry‐Allen, K. M., Xu, J., Anaya, M. A., Uehara, S., & Celnik, P. A. (2020) · Neurorehabilitation and neural repair · doi:10.1177/1545968320939563 · Cited by 56 · see citing works
Noradrenergic modulation of hemiplegia: Facilitation and maintenance of recovery
Feeney, D. M., Smet, A. M. D., & Rai, S. (2004) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-2004-00274 · Cited by 34 · see citing works
Fluoxetine to improve functional outcomes in patients after acute stroke: the FOCUS RCT
Dennis, M. S., Forbes, J., Graham, C., Hackett, M. L., Hankey, G. J., House, A. O., Lewis, S. C., Lundström, E., Sandercock, P. A., & Mead, G. E. (2020) · Health Technology Assessment · doi:10.3310/hta24220 · Cited by 22 · see citing works
A single, clinically relevant dose of the GABAB agonist baclofen impairs visuomotor learning
Johnstone, A., Grigoras, I., Petitet, P., Capitão, L. P., & Stagg, C. J. (2020) · The Journal of Physiology · doi:10.1113/jp280378 · Cited by 15 · see citing works
Self-citationTime for the next stage of stroke recovery trials
Kwakkel, G., Meskers, C. G. M., & Ward, N. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30218-0 · Cited by 14 · see citing works
Self-citationNadeau, S. E., Lu, X., Dobkin, B. H., Wu, S. S., Dai, Y. E., Duncan, P. W., & and LEAPS Investigative Team (2012) · International Journal of Stroke · doi:10.1111/j.1747-4949.2012.00920.x · Cited by 13 · see citing works
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An integrated measure of GABA to characterize post-stroke plasticity
Paparella, I., Vandewalle, G., Stagg, C. J., & Maquet, P. (2023) · NeuroImage Clinical · doi:10.1016/j.nicl.2023.103463 · Cited by 28 · see citing works
Reducing disability after stroke
Markus, H. S. (2022) · International Journal of Stroke · doi:10.1177/17474930221080904 · Cited by 23 · see citing works
Harnessing cortical plasticity via gabapentinoid administration promotes recovery after stroke
Tedeschi, A., Larson, M. J. E., Zouridakis, A., Mo, L., Bordbar, A., Myers, J. M., Qin, H. Y., Rodocker, H. I., Fan, F., Lannutti, J. J., et al. (2022) · Brain · doi:10.1093/brain/awac103 · Cited by 23 · see citing works
Grigoras, I., Geist, E., Johnstone, A., Clarke, W. T., Emir, U. E., Nettekoven, C., Levenstein, J. M., Capitão, L. P., & Stagg, C. J. (2025) · Imaging Neuroscience · doi:10.1162/imag.a.979 · Cited by 1 · see citing works
Self-citationRehabilitation von Menschen mit einem Schlaganfall
Frommelt, P., & Meinhart, M. (2024) · Springer eBooks · doi:10.1007/978-3-662-66957-0_29
- Authors
- Johnstone, A., Brander, F., Kelly, K., Bestmann, S., & Ward, N.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- Corresponding author
- Johnstone, Ainslie
- Venue
- International Journal of Stroke
- Publisher
- SAGE Publications
- Published
- 2021-04-09
- Volume
- 17
- Issue
- 3
- Pages
- 269-281
- ISSN
- 1747-4930 (ISSN-L)
- 1747-4949
- PMC
- PMC8864335
- OpenAlex
- W3136752353
- Cited by
- 5
- References
- 42
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Stroke (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Dunhill Medical Trust (550660)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Medical Practices and Rehabilitation
- Health Sciences › Medicine › Neurology › Botulinum Toxin and Related Neurological Disorders
- Keywords
- stroke, brain injury, antidepressants, GABA agonists, antiepileptic drugs, upper limb function, Fugl-Meyer Assessment, Chedoke Arm and Hand Activity Inventory, Action Research Arm Test
- MeSH terms
- Stroke Rehabilitation, Aftercare, Central Nervous System, Humans, Male, Middle Aged, Patient Discharge, Drug Prescriptions, Retrospective Studies, Treatment Outcome, Recovery of Function, Stroke, Upper Extremity
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