Successful antipsychotic dose tapering leading to better cognition in patients with remitted psychosis: Results of Guided Antipsychotic Reduction to Reach Minimum Effective Dose (GARMED) trial

In patients with remitted psychosis, the dosage of antipsychotics can be lowered without increased risk of relapse. Whether dose tapering can lead to improved cognition is unclear. We compared changes in cognitive performance between patients undergoing dose tapering and those receiving a fixed maintenance dose. A 2-year prospective trial of patients with stable schizophrenia-related psychotic disorders was conducted: one group received guided dose reduction (GDR) and one group received maintenance treatment. Cognitive function was assessed using the Wechsler Adult Intelligence Scale-Third Edition, Mandarin Chinese version, at baseline, 1, and 2 years. The relations between the ratio of reduced dose and the extent of cognitive improvement were examined by Spearman's correlation coefficient. We also examined cognitive performance between aripiprazole (ARI) users and non-ARI users. GDR patients exhibited significantly greater improvements in total intellectual quotient (IQ), particularly working memory, and information and arithmetic subtest scores, with no significant difference in relapse rates between groups. Statistically significant dose-response correlations were found between the degree of dose reduction and improvements in total IQ (n = 72, r = 0.242, p = 0.041), Working Memory Index (n = 72, r = 0.284, p = 0.016), and Arithmetic subtest (n = 72, r = 0.295, p = 0.012). There were no differences in cognitive changes between ARI users and non-users. Lowering antipsychotic dosage may ameliorate patient performance in several cognitive domains. This finding is worthy of consideration while evaluating the risk-to-benefit ratio of tapering antipsychotics in patients with remitted psychosis.