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In addition, the mean 55 ms improvement in CPT reaction time for the risperidone + guanfacine group showed a trend difference from the placebo + risperidone group (U 12, p .1) (Figure 3 ). While the combination of risperidone and guanfacine produced an improvement of 5 words on serial learning and 1.5 words on delayed recall from the RAVLT, and a mean 40 s improvement on the Trails B test, these improvements were not different in magnitude from that associated with the risperidone and placebo combination. Finally, no improvement on verbal fluency or digit span distraction test performance was associated with the guanfacine and risperidone combination.

Study selection Randomised controlled trials comparing dual blockers of the renin angiotensin system with monotherapy, reporting data on either long term efficacy (1 year) or safety events (4 weeks), and with a sample size of at least 50. Analysis was stratified by trials with patients with heart failure versus patients without heart failure.Results 33 randomised controlled trials with 68405 patients (mean age 61 years, 71% men) and mean duration of 52 weeks were included. Dual blockade of the renin angiotensin system was not associated with any significant benefit for all cause mortality (relative risk 0.97, 95% confidence interval 0.89 to 1.06) and cardiovascular mortality (0.96, 0.88 to 1.05) compared with monotherapy.

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