Effects of the First Exposure of Antipsychotics on Serum Albumin in Adolescents and Young Adults With First-Episode Schizophrenia
Cardiometabolic risk caused by antipsychotics is clinically concerning.1–3 In the early stage of antipsychotic treatment, weight gain and increased lipid metabolic risk are commonly seen; however, findings concerning glucose metabolism have been controversially reported,1,4–7 and few studies have reported the effects of antipsychotics on protein metabolism, for example, the serum albumin level.1,5,7
In a natural real-world drug-naive first-episode schizophrenia (FES) inpatient cohort, we reported that levels of fasting glucose, serum albumin, and urea nitrogen were significantly decreased after short-term antipsychotics exposure.7 However, widely distributed age intervals of that cohort (13–60 years) as an important confounding factor would have physiologically affected the metabolic indices. Hence, we analyzed the effects of first exposure to antipsychotics on metabolism by combining an independent cohort (99 cases) of drug-naive FES inpatients collected by the Adolescents Psychotic Division of the First Affiliated Hospital of Zhengzhou University with our previous drug-naive FES cases of 14- to 24-year-old (243 cases).7 The diagnosis was made by 2 experienced psychiatrists trained to use the Chinese version of the International Classification of Diseases, 10th Revision, and confirmed by the third senior psychiatrist. Clinical treatment followed the Psychotic Disorder Treatment Guideline (China, the first edition), which is a national standard guideline in China. The research protocol has been approved by the ethics committees of the above hospitals. The inclusion criteria, the exclusion criteria, and detailed data collection process were described before.7
Serum and plasma samples were collected between 6:00 and 7:00 AM following an overnight fast. All the samples were sent to the clinical laboratory center of the hospital for testing on the same day of blood withdrawal. All these parameters were routinely measured by a technician blind to the clinical situation using the Automatic Biochemical Analyzer (Beckman Coulter AU5811; Beckman Coulter, Inc, Indianapolis, IN). The detailed methods for serum biochemistry metabolic indicators are listed below: albumin (bromocresol green [BCG]), total protein (biuret), triglyceride (glycerol lipase oxidase [GPO-PAP]), total cholesterol (the enzymatic cholesterol oxidase, paminophenazone, peroxidase [CHOD-PAP]), low-density lipoprotein cholesterol (surfactant direct eliminating [SUR]), high-density lipoprotein cholesterol (HDL-C; catalase eliminating [CAT]).
Categorical and continuous metabolic variables were compared between baseline and after treatment, using χ2 test and paired t test, as appropriate. Correlation between changes (Δ: value after exposure − value at baseline) in lipid indicators and albumin was examined by bivariate correlation (Pearson correlation coefficients) analysis. Statistical analysis was conducted using the Statistical Package for Social Sciences (SPSS version 17.0; Chicago, IL). Statistical significance was defined as P < 0.05.
A total of 342 drug-naive FES inpatients 14 to 24 years old, including 145 male (42.4%), were included. The average age was 18.9 (SD, 2.7) years, with a median of 18.0 years. The mean illness duration was 6.0 (SD, 8.0) months, with a median of 2 months. For the effects on body mass index (BMI) and blood pressure, antipsychotic exposure duration was defined as the in-hospital stay period, which was 46.1 ± 23.5 days (median, 44.5 days). For the effects on blood metabolic measurements, antipsychotic exposure period was upon the duration between the baseline and the second blood draw, which was 22.4 ± 10.8 days (median, 20.0 days). Among all the inpatients, cases (42.7%) received polypharmacy. Comedications consisted mainly of antipsychotics (12.6%), antidepressants (15.0%), and mood stabilizers (22.0%).
Upon the earliest stage of antipsychotic/treatment exposure, the lipid metabolic indicators (the mean levels of triglycerides, triglycerides–to–HDL-C ratio, and the prevalence of dyslipidemia) and BMI significantly increased as expected. Meanwhile, patients had modestly but statistically significantly lower levels of fasting glucose, serum total proteins, albumin, and urea nitrogen than those at baseline (see Table 1). No patients had clinically identified hypoalbuminemia (albumin < 35 g/L).