Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents.
BACKGROUND
Cardiometabolic effects of second-generation antipsychotic medications are concerning but have not been sufficiently studied in pediatric and adolescent patients naive to antipsychotic medication.


OBJECTIVE
To study the association of second-generation antipsychotic medications with body composition and metabolic parameters in patients without prior antipsychotic medication exposure.


METHODS
Nonrandomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted between December 2001 and September 2007 at semi-urban, tertiary care, academic inpatient and outpatient clinics in Queens, New York, with a catchment area of 4.5-million individuals. Of 505 youth aged 4 to 19 years with 1 week or less of antipsychotic medication exposure, 338 were enrolled (66.9%). Of these patients, 272 had at least 1 postbaseline assessment (80.5%), and 205 patients [corrected] completed the study (60.7%). Patients had mood spectrum (n = 130; 47.8%), schizophrenia spectrum (n = 82; 30.1%), and disruptive or aggressive behavior spectrum (n = 60; 22.1%) disorders. Fifteen patients who refused participation or were nonadherent served as a comparison group.


METHODS
Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks.


METHODS
Weight gain and changes in lipid and metabolic parameters.


RESULTS
After a median of 10.8 weeks (interquartile range, 10.5-11.2 weeks) of treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7 kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by 4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the minimal weight change of 0.2 kg (95% CI, -1.0 to 1.4 kg) in the untreated comparison group (n = 15). With olanzapine and quetiapine, respectively, mean levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to 24.3 mg/dL] P < .001 and 9.1 mg/dL [95% CI, 0.4 to 17.7 mg/dL] P = .046), triglycerides (24.3 mg/dL [95% CI, 9.8 to 38.9 mg/dL] P = .002 and 37.0 mg/dL [95% CI, 10.1 to 63.8 mg/dL] P = .01), non-high-density lipoprotein (HDL) cholesterol (16.8 mg/dL [95% CI, 9.3 to 24.3 mg/dL] P < .001 and 9.9 mg/dL [95% CI, 1.4 to 18.4 mg/dL] P = .03), and ratio of triglycerides to HDL cholesterol (0.6 [95% CI, 0.2 to 0.9] P = .002 and (1.2 [95% CI, 0.4 to 2.0] P = .004). With risperidone, triglycerides increased significantly (mean level, 9.7 mg/dL [95% CI, 0.5 to 19.0 mg/dL]; P = .04). Metabolic baseline-to-end-point changes were not significant with aripiprazole or in the untreated comparison group.


CONCLUSIONS
First-time second-generation antipsychotic medication use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 antipsychotic medications.
Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, 75-59 263rd St, Glen Oaks, NY 11004, USA. ccorrell@lij.edu
Christoph U
CU
Correll
Peter
P
Manu
Vladimir
V
Olshanskiy
Barbara
B
Napolitano
John M
JM
Kane
Anil K
AK
Malhotra
D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D008055:Lipids; D010879:Piperazines; D015363:Quinolones; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000068180:Aripiprazole; D018967:Risperidone; D000077152:Olanzapine