title: Pharmacological interventions for unilateral spatial neglect after stroke.
abstract: BACKGROUND
  Unilateral spatial neglect (USN) is characterized by the inability to report or respond to people or objects presented on the side contralateral to the lesioned side of the brain and has been associated with poor functional outcomes and long stays in hospitals and rehabilitation centers. Pharmacological interventions (medical interventions only, use of drugs to improve the health condition), such as dopamine and noradrenergic agonists or pro-cholinergic treatment, have been used in people affected by USN after stroke, and effects of these treatments could provide new insights for health professionals and policy makers.
  
  
  OBJECTIVE
  To evaluate the effectiveness and safety of pharmacological interventions for USN after stroke.
  
  
  METHODS
  We searched the Cochrane Stroke Group Trials Register (April 2015), the Cochrane Central Register of Controlled Trials (April 2015), MEDLINE (1946 to April 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to April 2015), EMBASE (1980 to April 2015), PsycINFO (1806 to April 2015) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to April 2015). We also searched trials and research registers, screened reference lists, and contacted study authors and pharmaceutical companies (April 2015).
  
  
  METHODS
  We included randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs) of pharmacological interventions for USN after stroke.
  
  
  METHODS
  Two review authors independently assessed risk of bias in the included studies and extracted data.
  
  
  RESULTS
  We included in the review two studies with a total of 30 randomly assigned participants. We rated the quality of the evidence as very low as the result of study limitations, small numbers of events, and small sample sizes, with imprecision in the confidence interval (CI). We were not able to perform meta-analysis because of heterogeneity related to the different interventions evaluated between included studies. Very low-quality evidence from one trial (20 participants) comparing effects of rivastigmine plus rehabilitation versus rehabilitation on overall USN at discharge showed the following: Barrage (mean difference (MD) 0.30, 95% confidence interval (CI) -0.18 to 0.78); Letter Cancellation (MD 10.60, 95% CI 2.07 to 19.13); Sentence Reading (MD 0.20, 95% CI -0.69 to 1.09), and the Wundt-Jastrow Area Illusion Test (MD -4.40, 95% CI -8.28 to -0.52); no statistical significance was observed for the same outcomes at 30 days' follow-up. In another trial (10 participants), study authors showed statistically significant reduction in omissions in the three cancellation tasks under transdermal nicotine treatment (mean number of omissions 2.93 ± 0.5) compared with both baseline (4.95 ± 0.8) and placebo (5.14 ± 0.9) (main effect of treatment condition: F (2.23) = 11.06; P value < 0.0001). One major adverse event occurred in the transdermal nicotine treatment group, and treatment was discontinued in the affected participant. None of the included trials reported data on several of the prespecified outcomes (falls, balance, depression or anxiety, poststroke fatigue, and quality of life).
  
  
  CONCLUSIONS
  The quality of the evidence from available RCTs was very low. The effectiveness and safety of pharmacological interventions for USN after stroke are therefore uncertain. Additional large RCTs are needed to evaluate these treatments.
authors.affiliation: Department of Neurology, Botucatu Medical School, Universidade Estadual Paulista (UNESP), District of Rubiao Junior, Botucatu, São Paulo, Brazil.
authors.forename: Gustavo José
authors.initials: GJ
authors.lastname: Luvizutto
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bazan
authors.forename: Gabriel Pereira
authors.initials: GP
authors.lastname: Braga
authors.forename: Luiz Antônio de Lima
authors.initials: LA
authors.lastname: Resende
authors.forename: Silméia Garcia Z
authors.initials: SG
authors.lastname: Bazan
authors.forename: Regina
authors.initials: R
authors.lastname: El Dib
mesh_terms: D000279:Administration, Cutaneous; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009538:Nicotine / Q000008:administration & dosage / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010468:Perceptual Disorders / Q000188:drug therapy* / Q000534:rehabilitation; D016032:Randomized Controlled Trials as Topic; D000068836:Rivastigmine / Q000627:therapeutic use*; D020521:Stroke / Q000150:complications*; D000071939:Stroke Rehabilitation
chemical_list: D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D009538:Nicotine; D000068836:Rivastigmine