An Archival, Follow-Forward Exploration of the Metabolic Syndrome in Randomly Selected, Clozapine-Treated Patients

Richard C. Josiassen
Dawn M. Filmyer
Jessica L. Curtis
Rita A Shaughnessy
Adlai Joseph
Ronald L. Parson
Margit Kacso
Jason Fedde
Maurice D. Cornelius
Maurice Joseph
Jonathan Weinstein
Nina Skuban
Tim Victor


Objectives: Cross-sectional studies indicate that clozapine is associated with unusually high rates of the metabolic syndrome (MetS) in schizophrenia. These studies cannot address the extent to which schizophrenia or other factors are major risks for the MetS, independent of clozapine exposure. The objectives of this study were to longitudinally examine metabolic risk factors before and after clozapine initiation: 1) to determine MetS prevalence rates during firstgeneration antipsychotic (FGA) and clozapine treatment; 2) to identify metabolic changes contributing to the MetS; and, 3) to evaluate the extent to which prior treatment and subject variables contributed to increased MetS prevalence rates. Methods: Using an archival, follow-forward design, metabolic risk factors were sampled on a quarterly basis from medical records of twenty-five randomly selected inpatients. The sampling period was six years (three years of FGA and three years of clozapine). All subjects had been treated only with FGAs prior to clozapine exposure. Results: During clozapine treatment 16 of 25 (64%) subjects met MetS criteria; however, half (8 of 16) of the subjects already met MetS criteria during FGA treatment. Increased MetS prevalence with clozapine resulted from increases in fasting glucose and triglyceride levels and increased systolic BP. BMI was stable over time. Gender, age of clozapine initiation, and clozapine dose and duration may have contributed to long-term MetS risk. Conclusions: Clozapine-treated patients are at increased risk for the MetS. When observed longitudinally, however, it is clear that a significant proportion of the metabolic risk involves factors other than clozapine exposure alone.