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The effectiveness of dopamine agonists for treatment of neuropsychiatric symptoms post brain injury and stroke

Published online by Cambridge University Press:  08 April 2015

Musa Basseer Sami  and
Rafey Faruqui
Musa Basseer Sami*
Affiliation:
Canterbury and Coastal Community Mental Health Team, 41 Old Dover Road, Canterbury, Kent, CT1 3HU, UK
Rafey Faruqui
Affiliation:
Consultant Neuropsychiatrist, St Andrew’s Healthcare, Northampton, UK
*
Musa Basseer Sami, Canterbury and Coastal Community Mental Health Team, 41 Old Dover Road, Canterbury, Kent, CT1 3HU, UK. Tel: +01227 597100; Fax: +01227 597120; E-mail: musasami@doctors.org.uk
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Abstract

Objective

Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials.

Methods

We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function. Databases searched were: Medline, EMBASE, and PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP Medical database were also searched. All identified studies, were further hand-searched.

Results

We identified six studies providing data on 227 participants, 150 of whom received dopaminergic therapy. Trials were compromised by cross-over design, inadequate wash out period, small numbers and heterogeneous outcome measures. However one good quality RCT demonstrates the efficacy of amantadine in behavioural management. One further RCT shows methylphenidate-levodopa is efficacious for mood post-stroke. One study shows rotigotine to improve hemi-inattention caused by prefrontal damage.

Conclusion

Our systematic review demonstrates an evolving evidence base to suggest some benefits in agitation and aggression, mood and attentional deficits. However, there are key limitations of the studies undertaken to date involving small numbers of participants, heterogeneous outcome measures, and variable study designs. There is a need for on-going large prospective double-blind RCTs in these medications using standardised criteria and outcomes to fully understand their effectiveness in this patient group.

Keywords

agitationapathydopaminestroketraumatic brain injury
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 27 , Issue 6 , December 2015 , pp. 317 - 326
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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References

1 Murray, CJ, Vos, T, Lozano, R et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2197–2223.Google Scholar
2 Vos, T, Flaxman, AD, Naghavi, M et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2163–2196.Google Scholar
3 Roozenbeek, B, Maas, AI, Menon, DK. Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol 2013;9:231–236.Google Scholar
4 Ma, VY, Chan, L, Carruthers, KJ. Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arch Phys Med Rehabil 2014;95:986–995. e1.Google Scholar
5 Bhalerao, SU, Geurtjens, C, Thomas, GR et al. Understanding the neuropsychiatric consequences associated with significant traumatic brain injury. Brain Inj 2013;27:767–774.Google Scholar
6 Hackett, ML, Kohler, S, O’Brien, JT et al. Neuropsychiatric outcomes of stroke. Lancet Neurol 2014;13:525–534.Google Scholar
7 Brannan, T, Weinberger, J, Knott, P et al. Direct evidence of acute, massive striatal dopamine release in gerbils with unilateral strokes. Stroke 1987;18:108–110.Google Scholar
8 Kawano, T, Tsutsumi, K, Miyake, H et al. Striatal dopamine in acute cerebral ischemia of stroke-resistant rats. Stroke 1988;19:1540–1543.Google Scholar
9 Shin, SS, Bray, ER, Zhang, CQ et al. Traumatic brain injury reduces striatal tyrosine hydroxylase activity and potassium-evoked dopamine release in rats. Brain Res 2011;1369:208–215.Google Scholar
10 Bales, JW, Wagner, AK, Kline, AE et al. Persistent cognitive dysfunction after traumatic brain injury: a dopamine hypothesis. Neurosci Biobehav Rev 2009;33:981–1003.Google Scholar
11 Ruscher, K, Kuric, E, Wieloch, T. Levodopa treatment improves functional recovery after experimental stroke. Stroke 2012;43:507–513.Google Scholar
12 Kline, AE, Massucci, JL, Ma, X et al. Bromocriptine reduces lipid peroxidation and enhances spatial learning and hippocampal neuron survival in a rodent model of focal brain trauma. J Neurotrauma 2004;21:1712–1722.Google Scholar
13 Goldstein, LB. Basic and clinical studies of pharmacologic effects on recovery from brain injury. J Neural Transplant Plast 1993;4:175–192.Google Scholar
14 Donnemiller, E, Brenneis, C, Wissel, J et al. Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM. Eur J Nucl Med 2000;27:1410–1414.Google Scholar
15 Gualtieri, T, Chandler, M, Coons, TB et al. Amantadine: a new clinical profile for traumatic brain injury. Clin Neuropharmacol 1989;12:258–270.Google Scholar
16 Andersson, S, Berstad, J, Finset, A et al. Amantadine in cognitive failure in patients with traumatic head injuries. Tidsskr Nor Laegeforen 1992;112:2070–2072.Google Scholar
17 Nickels, JL, Schneider, WN, Dombovy, ML et al. Clinical use of amantadine in brain injury rehabilitation. Brain Inj 1994;8:709–718.Google Scholar
18 Kraus, MF, Maki, PM. Effect of amantadine hydrochloride on symptoms of frontal lobe dysfunction in brain injury: case studies and review. J Neuropsychiatry Clin Neurosci 1997;9:222–230.Google Scholar
19 Powell, JH, Al-Adawi, S, Morgan, J et al. Motivational deficits after brain injury: effects of bromocriptine in 11 patients. J Neurol Neurosurg Psychiatry 1996;60:416–421.Google Scholar
20 Kraus, MF, Smith, GS, Butters, M et al. Effects of the dopaminergic agent and NMDA receptor antagonist amantadine on cognitive function, cerebral glucose metabolism and D2 receptor availability in chronic traumatic brain injury: a study using positron emission tomography (PET). Brain Inj 2005;19:471–479.Google Scholar
21 Alexander, MP. Chronic akinetic mutism after mesencephalic-diencephalic infarction: remediated with dopaminergic medications. Neurorehabil Neural Repair 2001;15:151–156.Google Scholar
22 Kohno, N, Abe, S, Toyoda, G et al. Successful treatment of post-stroke apathy by the dopamine receptor agonist ropinirole. J Clin Neurosci 2010;17:804–806.Google Scholar
23 Napolitano, E, Elovic, EP, Qureshi, AI. Pharmacological stimulant treatment of neurocognitive and functional deficits after traumatic and non-traumatic brain injury. Med Sci Monit 2005;11:RA212–RA220.Google Scholar
24 Wheaton, P, Mathias, JL, Vink, R. Impact of pharmacological treatments on cognitive and behavioral outcome in the postacute stages of adult traumatic brain injury: a meta-analysis. J Clin Psychopharmacol 2011;31:745–757.Google Scholar
25 Frenette, AJ, Kanji, S, Rees, L et al. Efficacy and safety of dopamine agonists in traumatic brain injury: a systematic review of randomized controlled trials. J Neurotrauma 2012;29:1–18.Google Scholar
26 Jadad, AR, Moore, RA, Carroll, D et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12.Google Scholar
27 Delbari, A, Salman-Roghani, R, Lokk, J. Effect of methylphenidate and/or levodopa combined with physiotherapy on mood and cognition after stroke: a randomized, double-blind, placebo-controlled trial. Eur Neurol 2011;66:7–13.Google Scholar
28 Schneider, WN, Drew-Cates, J, Wong, TM et al. Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury: an initial double-blind placebo-controlled study. Brain Inj 1999;13:863–872.Google Scholar
29 Meythaler, JM, Brunner, RC, Johnson, A et al. Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial. J Head Trauma Rehabil 2002;17:300–313.Google Scholar
30 Hammond, FM, Bickett, AK, Norton, JH et al. Effectiveness of amantadine hydrochloride in the reduction of chronic traumatic brain injury irritability and aggression. J Head Trauma Rehabil 2014;29:391–399.Google Scholar
31 Whyte, J, Vaccaro, M, Grieb-Neff, P et al. The effects of bromocriptine on attention deficits after traumatic brain injury: a placebo-controlled pilot study. Am J Phys Med Rehabil 2008;87:85–99.Google Scholar
32 Gorgoraptis, N, Mah, YH, Machner, B et al. The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke. Brain 2012;135(Pt 8):2478–2491.Google Scholar
33 Leone, H, Polsonetti, BW. Amantadine for traumatic brain injury: does it improve cognition and reduce agitation? J Clin Pharm Ther 2005;30:101–104.Google Scholar
34 Fleminger, S, Greenwood, RJ, Oliver, DL. Pharmacological management for agitation and aggression in people with acquired brain injury. Cochrane Database Syst Rev 2006;4:CD003299, doi: 10.1002/14651858.CD003299.pub2.Google Scholar
35 Wheaton, P, Mathias, JL, Vink, R. Impact of early pharmacological treatment on cognitive and behavioral outcome after traumatic brain injury in adults: a meta-analysis. J Clin Psychopharmacol 2009;29:468–477.Google Scholar
36 Saniova, B, Drobny, M, Kneslova, L et al. The outcome of patients with severe head injuries treated with amantadine sulphate. J Neural Transm 2004;111:511–514.Google Scholar
37 Kant, R, Duffy, JD, Pivovarnik, A. Prevalence of apathy following head injury. Brain Inj 1998;12:87–92.Google Scholar
38 Caeiro, L, Ferro, JM, Costa, J. Apathy secondary to stroke: a systematic review and meta-analysis. Cerebrovasc Dis 2013;35:23–39.Google Scholar
39 Wass, C, Pizzo, A, Sauce, B et al. Dopamine D1 sensitivity in the prefrontal cortex predicts general cognitive abilities and is modulated by working memory training. Learn Mem 2013;20:617–627.Google Scholar
40 Scheidtmann, K, Fries, W, M¸ller, F et al. Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study. Lancet 2001;358:787–790.Google Scholar