Children and youths who were treated with “atypical antipsychotic medications” (aripiprazole, olanzapine, quetiapine, or risperidone) gained substantial weight and had changes in their metabolism in a study reported by Christoph Correll and colleagues in the Journal of the American Medical Association. The drugs, which are used to treat childhood schizophrenia, bipolar disorder, and (sometimes) Autism, also caused changes in blood lipids.
The medications, which are also known as second generation antipsychotics, are marketed under the names shown in the table at the right.
On average, the children’s weight gains differed across the different medications, ranging from 8.5 kg with olanzapine to 4.4 kg with aripiprazole. For better than half of the children, the gains amounted to more than 7% of their body weight. Changes in the children’s metabolism varied by drug, too; olanzapine caused the largest problems and aripiprazole caused no changes in metabolism (e.g., cholesterol).
the study by Dr. Correll and colleagues extends other research. In particular, they studied only children who had not previously taken an anti-psychotic medication. This feature eliminates the possibility that changes observed with the medications could be attributed to them specifically, not to a combination of them and other factors.
In a commentary, Drs. Christopher Varley and Jon McClellan raise questions about the usefullness of these medications. Based on concerns about the research undergirding the effects of the medications. Dr. Correll and colleagues ended their article with this conclusion:
Our results, together with data from first-episode studies, suggest that guidelines for antipsychotic medication exposure for vulnerable pediatric and adolescent patients naive to antipsychotic medication should consider more frequent (eg, biannual) cardiometabolic monitoring after the first 3 months of treatment. Finally, in view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medications must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management.
Here’s the abstract of the study:
Context 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.
Design, Setting, and Patients 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 who 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.
Intervention Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks.
Main Outcome Measures 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.
Correll, C. U., Manu, P., Olshanskiy, V., Napolitano, B., Kane, J. M., & Malhotra, A. K. (2009). Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. Journal of the American Medical Association, 302, 1765-1773.
Varley, C. K., & McClellan, J. (2009). Implications of marked weight gain associated with atypical antipsychotic medications in children and adolescents Journal of American Medical Association, 302, 1811-1812.