Abstract: 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). 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.

Plain-language summary: Adults over 18 years of age, regardless of gender and ethnicity, with USN after stroke diagnosis measured by clinical examination or radiographically by computed tomography or magnetic resonance imaging, regardless of whether they were evaluated by any paper-and-pencil tests. We considered including people diagnosed with any type of stroke (ie, ischemic or hemorrhagic) from the acute phase (the first 24 to 72 hours) until one year after the stroke. We identified two studies involving 30 participants up to April 2015. We are uncertain as to whether comparison of different pharmacological interventions (rivastigmine, transdermal nicotine)showed an important effect on (1) the ability of people to recognize their paralyzed limb, and (2) independence in daily life functions after stroke, because results were imprecise and included studies did not report most of the predefined outcomes (ie, falls, balance, depression or anxiety, poststroke fatigue, and quality of life). We considered the quality of included studies to be reasonable. Given the small sample size and methodological limitations (participants were assigned in a successive manner in one study), no conclusions can be drawn regarding the effectiveness of pharmacological medications in USN after stroke. The quality of the evidence obtained from available randomized controlled trials was very low. The effectiveness and safety of pharmacological interventions for USN after stroke are therefore uncertain. Additional large randomized controlled trials are needed to evaluate these treatments.