Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients: The CATIE-AD study

Ling Zheng, Wendy J. Mack, Karen S. Dagerman, John K. Hsiao, Barry D. Lebowitz, Constantine G Lyketsos, T. Scott Stroup, David L. Sultzer, Pierre N. Tariot, Cheryl Vigen, Lon S. Schneider

Research output: Contribution to journalArticle

Abstract

Objective: The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects. Method: The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models. Results: Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., ≥7% of body weight) was seen among patients with antipsychotic use ≤12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and >24 weeks (OR=3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides. Conclusion: Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalAmerican Journal of Psychiatry
Volume166
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

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olanzapine
Antipsychotic Agents
Alzheimer Disease
Clinical Trials
Weight Gain
Odds Ratio
HDL Cholesterol
Blood Pressure
Risperidone
Waist Circumference
Blood Glucose
Fasting
Schizophrenia
Triglycerides
Outpatients
Logistic Models
Placebos
Body Weight
Lipids
Weights and Measures

ASJC Scopus subject areas

  • Psychiatry and Mental health

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Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients : The CATIE-AD study. / Zheng, Ling; Mack, Wendy J.; Dagerman, Karen S.; Hsiao, John K.; Lebowitz, Barry D.; Lyketsos, Constantine G; Stroup, T. Scott; Sultzer, David L.; Tariot, Pierre N.; Vigen, Cheryl; Schneider, Lon S.

In: American Journal of Psychiatry, Vol. 166, No. 5, 05.2009, p. 583-590.

Research output: Contribution to journalArticle

Zheng, L, Mack, WJ, Dagerman, KS, Hsiao, JK, Lebowitz, BD, Lyketsos, CG, Stroup, TS, Sultzer, DL, Tariot, PN, Vigen, C & Schneider, LS 2009, 'Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients: The CATIE-AD study', American Journal of Psychiatry, vol. 166, no. 5, pp. 583-590. https://doi.org/10.1176/appi.ajp.2008.08081218
Zheng, Ling ; Mack, Wendy J. ; Dagerman, Karen S. ; Hsiao, John K. ; Lebowitz, Barry D. ; Lyketsos, Constantine G ; Stroup, T. Scott ; Sultzer, David L. ; Tariot, Pierre N. ; Vigen, Cheryl ; Schneider, Lon S. / Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients : The CATIE-AD study. In: American Journal of Psychiatry. 2009 ; Vol. 166, No. 5. pp. 583-590.
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abstract = "Objective: The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects. Method: The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models. Results: Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., ≥7{\%} of body weight) was seen among patients with antipsychotic use ≤12 weeks (odds ratio [OR]=1.56, 95{\%} CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95{\%} CI=0.97 to 8.64), and >24 weeks (OR=3.38, 95{\%} CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides. Conclusion: Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely.",
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T2 - The CATIE-AD study

AU - Zheng, Ling

AU - Mack, Wendy J.

AU - Dagerman, Karen S.

AU - Hsiao, John K.

AU - Lebowitz, Barry D.

AU - Lyketsos, Constantine G

AU - Stroup, T. Scott

AU - Sultzer, David L.

AU - Tariot, Pierre N.

AU - Vigen, Cheryl

AU - Schneider, Lon S.

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N2 - Objective: The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects. Method: The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models. Results: Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., ≥7% of body weight) was seen among patients with antipsychotic use ≤12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and >24 weeks (OR=3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides. Conclusion: Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely.

AB - Objective: The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects. Method: The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models. Results: Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., ≥7% of body weight) was seen among patients with antipsychotic use ≤12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and >24 weeks (OR=3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides. Conclusion: Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely.

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