Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: prospective data from phase 1.
BACKGROUND
The metabolic syndrome (MS) is associated with increased risk for diabetes mellitus and coronary heart disease, and is highly prevalent among schizophrenia patients. Given concerns over antipsychotic metabolic effects, this analysis explored MS status and outcomes in phase 1 of the CATIE Schizophrenia Trial.


METHODS
The change in proportion of subjects with MS and individual criteria was compared between antipsychotic treatment groups, along with mean changes for individual criteria. Primary analyses examined subjects with fasting laboratory assessments at baseline and 3 months. Other analyses examined 3-month changes in MS status, waist circumference (WC), HDL cholesterol and blood pressure in all subjects, metabolic changes at the end of phase 1 participation (EOP), and repeated measures changes in HDL, blood pressure (BP) and WC over phase 1.


RESULTS
At 3 months, there were no significant between-drug differences for the change in proportion of subjects meeting MS status or individual MS criteria in the smaller fasting cohort (n = 281) or for those meeting criteria for parameters not dependent on fasting status (BP, HDL, WC) among all subjects (n=660). Among all subjects whose MS status could be determined at 3 months (n=660), MS prevalence increased for olanzapine (from 34.8% to 43.9%), but decreased for ziprasidone (from 37.7% to 29.9%) (p=.001). Although effect sizes varied across subgroups, at 3 months olanzapine and quetiapine had the largest mean increase in waist circumference (0.7 in. for both) followed by risperidone (0.4 in.), compared to no change for ziprasidone (0.0 in.) and a decrease in waist circumference for perphenazine (-0.4 in.). Olanzapine also demonstrated significantly different changes in fasting triglycerides at 3 months (+21.5 mg/dl) compared to ziprasidone (-32.1 mg/dl). EOP exposure data was obtained, on average, nine months from baseline for all metabolic variables. Results from EOP and repeated measures analyses were consistent with those at 3 months for mean changes in WC and fasting triglycerides, but between group differences emerged for HDL and SBP.


CONCLUSIONS
This large non-industry sponsored study confirms the differential metabolic effects between antipsychotics. Clinicians are advised to monitor all metabolic parameters, including WC, HDL and serum triglycerides, during antipsychotic treatment.
Meyer
Jonathan M
JM
Department of Psychiatry, University of California, San Diego, USA. jmmeyer@ucsd.edu
Davis
Vicki G
VG
Goff
Donald C
DC
McEvoy
Joseph P
JP
Nasrallah
Henry A
HA
Davis
Sonia M
SM
Rosenheck
Robert A
RA
Daumit
Gail L
GL
Hsiao
John
J
Swartz
Marvin S
MS
Stroup
T Scott
TS
Lieberman
Jeffrey A
JA
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000378:metabolism; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000453:epidemiology* / Q000378:metabolism; D011446:Prospective Studies; D012559:Schizophrenia / Q000188:drug therapy; D049629:Waist-Hip Ratio
D014150:Antipsychotic Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL