A randomised double-blind, placebo-controlled crossover study of single-dose guanfacine in unilateral neglect following stroke

Abstract

Objective Unilateral neglect is a post-stroke disorder that impacts negatively on functional outcome and lacks established, effective treatment. This multi-component syndrome is characterised by a directional bias of attention away from contralesional space, together with impairments in several cognitive domains, including sustained attention and spatial working memory. This study aims to test the effects of guanfacine, a noradrenergic alpha-2A agonist, on ameliorating aspects of neglect. Methods Thirteen right hemisphere stroke patients with leftward neglect were included in a randomised double- blind, placebo-controlled proof-of-concept crossover study that examined the effects of a single dose of guanfacine. Patients were tested on a computerised, time-limited cancellation paradigm, as well as tasks that independently assessed sustained attention and spatial working memory. Results On guanfacine, there was a statistically significant improvement in the total number of targets found on the cancellation task when compared to placebo (mean improvement of 5, out of a possible 64). However, there was no evidence of a change in neglect patients' directional attention bias. Furthermore, Bayesian statistical analysis revealed reliable evidence against any effects of guanfacine on search organisation and performance on our sustained attention and spatial working memory tasks. Conclusions Guanfacine improves search in neglect by boosting the number of targets found, but had no effects on directional bias, or search organisation; nor did it improve sustained attention or working memory on independent tasks. Further work is necessary to determine whether longer-term treatment with guanfacine may be effective for some neglect patients, and whether it affects functional outcome measures.