This study aimed to investigate whether antipsychotic medications can cause metabolic abnormalities independent of weight gain. Six hundred twenty-four patients treated with olanzapine and risperidone were enrolled. Body weight, body mass index (BMI), biochemical indicators of blood glucose and lipids, the proportion of patients who gained >
7% of their baseline weight, dyslipidemia, and dysglycemia were evaluated. The association between the prevalence of metabolic disturbances and groups was analyzed using logistic regression, adjusting confounding variables including age, sex, weight, duration and Chlorpromazine (CLO)-equivalent dosage. Assessments were conducted at baseline and 4, 8, and 24-weeks post-treatment. The rate of weight gain >
7% at 8-weeks was significantly higher than at 4-weeks in the total population (F = 49.02, p <
0.001) and in patients with abnormal metabolism (F = 29.97, p <
0.001). No significant differences were observed between follow-up time points in the 24-weeks. The proportion of abnormal blood lipids and glucose did not differ significantly between the 4-week and 8-week follow-ups. Logistic regression analyses revealed significant differences between olanzapine and risperidone groups regarding the prevalence of hypertriglyceridemia at week 4 ([adjusted odds ratio
aOR] = 1.710
95% [ confidence interval
CI] = 1.213-2.410) and week 8 ([aOR] = 1.594
95% [CI] = 0.859-2.957) and low LDL at week 4 ([aOR] = 1.772
95%[CI] = 1.014-3.097) and week 8 ([aOR] = 3.851
95%[CI] = 1.732-5.588). In conclusion, antipsychotics-induced metabolic abnormalities and weight gain are not fully synchronized, and metabolic abnormalities vary significantly across different atypical antipsychotic medication (AAP) groups, even after adjusting BMI. AAPs may have a direct effect on metabolic parameters.