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A comparison of the effects of olanzapine and risperidone versus placebo on ghrelin plasma levels.
J Clin Psychopharmacol. 2008 Feb; 28(1):21-6.JC

Abstract

To thoroughly investigate the phenomenon of atypical antipsychotic-associated weight gain, a feeding laboratory paradigm was developed that included obtaining plasma levels of the orexigenic peptide ghrelin that is associated with appetite and eating. This study is a randomized, double-blind, parallel group trial comparing the effects of a 2-week exposure to olanzapine, risperidone, or placebo on plasma ghrelin area under the plasma-time curve (AUC) in 28 healthy human subjects. Subjects were randomized to receive olanzapine, risperidone, or placebo and titrated over 4 days to 10 mg/d or 4 mg/d, respectively. The mean dose at end point was 8.6 + 1.8 mg/d for the olanzapine group and 2.8 + 0.8 mg/d for the risperidone group. Weight changes were significantly different between groups at end point (F2,44 = 10.193; P = 0.0001). The olanzapine group demonstrated a significant increase in weight at end point (2.25 + 1.84 kg) compared with placebo (0.13 + 1.05 kg; P = 0.007). Because of the small subject number, the comparisons between olanzapine and risperidone and risperidone and placebo did not reach statistical significance, although olanzapine's mean weight gain was numerically greater than that of risperidone (2.25 + 1.84 kg vs 1.10 + 0.99 kg) and risperidone's mean weight gain was numerically larger than placebo (1.10 + 0.99 kg vs 0.13 + 1.05 kg). The baseline adjusted Bonferroni corrected contrast of end point ghrelin AUC demonstrated a significant difference between groups (F2,24 = 4.40; P = 0.024), and the post hoc analysis revealed a significant decrease in ghrelin AUC for the olanzapine group in comparison with the risperidone group (P = 0.021) but not between risperidone and placebo or olanzapine and placebo. Ghrelin AUC values did not change significantly from baseline to end point in either of the other 2 groups. The difference between groups approached but did not reach significance (F2,23 = 3.299; P = 0.055) when body mass index change was included as a covariate, suggesting that the difference in ghrelin AUC change followed the change in body weight. Sedation associated with both active drugs (P = 0.006) and "stuffy nose" associated with risperidone (P = 0.020) were the only statistically different adverse reactions when compared with placebo. Thus, a human feeding laboratory paradigm using a brief exposure to atypical antipsychotics functions as a method to investigate pharmacologically induced weight gain and its association with changes in the orexigenic peptide ghrelin. This rejects the hypothesis that ghrelin levels are elevated by the antipsychotic and that this is a potential cause of the weight gain phenomenon.

Authors+Show Affiliations

Department of Clinical Neuroscience, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND, USA. jroerig@nrifargo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18204336

Citation

Roerig, James L., et al. "A Comparison of the Effects of Olanzapine and Risperidone Versus Placebo On Ghrelin Plasma Levels." Journal of Clinical Psychopharmacology, vol. 28, no. 1, 2008, pp. 21-6.
Roerig JL, Steffen KJ, Mitchell JE, et al. A comparison of the effects of olanzapine and risperidone versus placebo on ghrelin plasma levels. J Clin Psychopharmacol. 2008;28(1):21-6.
Roerig, J. L., Steffen, K. J., Mitchell, J. E., Crosby, R. D., & Gosnell, B. A. (2008). A comparison of the effects of olanzapine and risperidone versus placebo on ghrelin plasma levels. Journal of Clinical Psychopharmacology, 28(1), 21-6. https://doi.org/10.1097/jcp.0b013e3181613325
Roerig JL, et al. A Comparison of the Effects of Olanzapine and Risperidone Versus Placebo On Ghrelin Plasma Levels. J Clin Psychopharmacol. 2008;28(1):21-6. PubMed PMID: 18204336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A comparison of the effects of olanzapine and risperidone versus placebo on ghrelin plasma levels. AU - Roerig,James L, AU - Steffen,Kristine J, AU - Mitchell,James E, AU - Crosby,Ross D, AU - Gosnell,Blake A, PY - 2008/1/22/pubmed PY - 2008/3/28/medline PY - 2008/1/22/entrez SP - 21 EP - 6 JF - Journal of clinical psychopharmacology JO - J Clin Psychopharmacol VL - 28 IS - 1 N2 - To thoroughly investigate the phenomenon of atypical antipsychotic-associated weight gain, a feeding laboratory paradigm was developed that included obtaining plasma levels of the orexigenic peptide ghrelin that is associated with appetite and eating. This study is a randomized, double-blind, parallel group trial comparing the effects of a 2-week exposure to olanzapine, risperidone, or placebo on plasma ghrelin area under the plasma-time curve (AUC) in 28 healthy human subjects. Subjects were randomized to receive olanzapine, risperidone, or placebo and titrated over 4 days to 10 mg/d or 4 mg/d, respectively. The mean dose at end point was 8.6 + 1.8 mg/d for the olanzapine group and 2.8 + 0.8 mg/d for the risperidone group. Weight changes were significantly different between groups at end point (F2,44 = 10.193; P = 0.0001). The olanzapine group demonstrated a significant increase in weight at end point (2.25 + 1.84 kg) compared with placebo (0.13 + 1.05 kg; P = 0.007). Because of the small subject number, the comparisons between olanzapine and risperidone and risperidone and placebo did not reach statistical significance, although olanzapine's mean weight gain was numerically greater than that of risperidone (2.25 + 1.84 kg vs 1.10 + 0.99 kg) and risperidone's mean weight gain was numerically larger than placebo (1.10 + 0.99 kg vs 0.13 + 1.05 kg). The baseline adjusted Bonferroni corrected contrast of end point ghrelin AUC demonstrated a significant difference between groups (F2,24 = 4.40; P = 0.024), and the post hoc analysis revealed a significant decrease in ghrelin AUC for the olanzapine group in comparison with the risperidone group (P = 0.021) but not between risperidone and placebo or olanzapine and placebo. Ghrelin AUC values did not change significantly from baseline to end point in either of the other 2 groups. The difference between groups approached but did not reach significance (F2,23 = 3.299; P = 0.055) when body mass index change was included as a covariate, suggesting that the difference in ghrelin AUC change followed the change in body weight. Sedation associated with both active drugs (P = 0.006) and "stuffy nose" associated with risperidone (P = 0.020) were the only statistically different adverse reactions when compared with placebo. Thus, a human feeding laboratory paradigm using a brief exposure to atypical antipsychotics functions as a method to investigate pharmacologically induced weight gain and its association with changes in the orexigenic peptide ghrelin. This rejects the hypothesis that ghrelin levels are elevated by the antipsychotic and that this is a potential cause of the weight gain phenomenon. SN - 0271-0749 UR - https://www.unboundmedicine.com/medline/citation/18204336/A_comparison_of_the_effects_of_olanzapine_and_risperidone_versus_placebo_on_ghrelin_plasma_levels_ L2 - http://dx.doi.org/10.1097/jcp.0b013e3181613325 DB - PRIME DP - Unbound Medicine ER -