Associations between second-generation antipsychotics and metabolic outcomes in patients with schizophrenia and metabolic abnormalities

Second-generation antipsychotics (SGAs) were found to have varying metabolic side-effects for patients with schizophrenia, while no studies have examined the associations between adding or switching low-risk SGAs and metabolic outcomes. This real-world observational study aimed to examine the association of adding or switching to low-risk SGAs with metabolic syndrome and metabolic abnormalities for patients with schizophrenia from 25 healthcare organizations across Zhejiang Province, China. Participants were dichotomized into the low-risk SGAs group and the high/intermediate SGAs group according to whether adding or switching to low-risk SGAs. A 1:1 propensity score matching (PSM) using a nearest-neighbor method was conducted to balance the baseline characteristics between groups. The mean [standard deviation (SD)] age of included patients was 50.0 (12.4) years, and 288 (37.7%) were women. The PSM yielded 223 matched pairs, with no between-group differences in baseline characteristics. Compared to the high/intermediate SGAs group, the low-risk SGAs group showed consistent decreases in the proportion of participants with metabolic syndrome [e.g., at 6 months: risk differences = 19.28%, 95% confidence interval (CI) = -28.19% to -10.38%; odds ratio = 0.47, 95% CI = 0.30 to 0.72] and the number of metabolic abnormalities [e.g., at 6 months: mean difference (MD) = -0.52, 95% CI = -0.75 to -0.29; relative risk = 0.79, 95% CI = 0.71 to 0.87]. The low-risk SGAs group presented significant improvement in metabolic parameters, including lower levels of weight, glucose and triglyceride (e.g., for triglycerise, (MD = -0.41 mmol/L, 95% CI = -0.61 to -0.21 mmol/L at 6 months), compared to the high/intermediate risk SGAs group. These assocaitions were more pronounced in those with no comorbid physical conditions, lower BMI, shorter duration and reporting smoking or drinking. Adding or switching to low-risk antipsychotics was associated with a decrease in metabolic outcomes, which can be considered as an appropriate secondary prevention strategy for patients with both schizophrenia and metabolic abnormalities.