A Comparison of the Effects of Olanzapine and Risperidone Versus Placebo on Eating Behaviors

North Dakota State University, Fargo, North Dakota, United States
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 11/2005; 25(5):413-8. DOI: 10.1097/
Source: PubMed


To thoroughly investigate the phenomenon of atypical antipsychotic associated weight gain, a feeding laboratory paradigm was developed. This study is a randomized, double-blind, parallel group trial comparing the tolerability and effects of a two-week exposure to olanzapine, risperidone or placebo on weight, resting energy expenditure (REE), and eating behaviors in 48 healthy human subjects. Subjects were randomized to receive olanzapine, risperidone, or placebo and titrated over four days to 10 mg/d, or 4 mg/d, respectively. The mean dose at endpoint was 8.75 mg/day for the olanzapine group and 2.88 mg/d risperidone group. Weight changes were significantly different between groups at midpoint (F = 5.477, df = 2, 44, P = .0001). The olanzapine group demonstrated a significant increase in weight at midpoint (1.59 + 1.80 kg, P = .002) and endpoint (2.25 + 1.62 kg, P = .0001) compared to placebo and at endpoint compared to risperidone (1.05 + 1.15 kg, P = .015). Resting energy expenditures corrected for fat free mass did not reveal any differences between groups. Olanzapine subjects demonstrated significantly more dry mouth and sedation versus placebo while risperidone subjects experienced significantly more sedation, dry mouth, dizziness stuffy nose and restlessness than placebo and more dizziness and stuffy nose versus olanzapine subjects. Thus, a human feeding lab paradigm utilizing a brief exposure to atypical antipsychotics functions as a method to investigate pharmacologically induced weight gain.

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    • "patients, it would be expected to result in reduced REE. However, clinical studies failed to observe any reductions in REE (Gothelf et al., 2002; Graham et al., 2005; Roerig et al., 2005; Vidarsdottir et al., 2010) and one study even reported an increase in REE (Fountaine et al., 2010). This suggests that, if olanzapine does reduce thermogenesis in humans, any resulting reduction in REE is either negligible, or compensated for by a different process that increases REE. "
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    ABSTRACT: The second-generation antipsychotic drug olanzapine has become a widely prescribed drug in the treatment of schizophrenia and bipolar disorder. Unfortunately, its therapeutic benefits are partly outweighed by significant weight gain and other metabolic side effects, which increase the risk for diabetes and cardiovascular disease. Because olanzapine remains superior to other antipsychotic drugs that show less weight gain liability, insight into the mechanisms responsible for olanzapine-induced weight gain is crucial if it is to be effectively addressed. Over the past few decades, several groups have investigated the effects of olanzapine on energy balance using rat models. Unfortunately, results from different studies have not always been consistent and it remains to be determined which paradigms should be used in order to model olanzapine-induced weight gain most accurately. This review summarizes the effects of olanzapine on energy balance observed in different rat models and discusses some of the factors that appear to contribute to the inconsistencies in observed effects. In addition it compares the effects reported in rats with clinical findings to determine the predictive validity of different paradigms.
    The International Journal of Neuropsychopharmacology 10/2013; 17(01):1-18. DOI:10.1017/S146114571300093X · 4.01 Impact Factor
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    • "The surge in studies of dopamine and the role of its transport and receptor genes in feeding and other reward-driven behaviors such as ethanol consumption , gambling, drug-taking, and obesity strongly points to evidence of reward-related phenotypes (Noble, St. Jeor, et al., 1994). Support for the role of dopamine in human feeding behavior is evidenced in part by the anorexigenic action of dopamine agonists (Goldfield, Lorello, & Doucet, 2007; Leddy et al., 2004; Schertz, Adesman, Alfieri, & Bienkowski, 1996) and by the orexigenic action of dopamine antagonists (Roerig et al., 2005; Ruetsch, Viala, Bardou, Martin, & Vacheron, 2005). Dopamine is also involved in motor control and motivation (Salamone, Correa, Mingote, & Weber, 2005), and there is a body of evidence to suggest that dopaminergic activity in the brain is related to voluntary physical activity (for review see Knab and Lightfoot (2010)). "
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    ABSTRACT: Introduction: Polymorphisms of the dopamine receptor D2 (DRD2) gene have been associated with obesity phenotypes. Our aim was to examine if the genotype of TaqIA Restriction Fragment Length Polymorphism (RFPL) was related to an attenuated weight loss response or to changes in energy expenditure (EE) and food preference before and after weight loss. methods: Obese post-menopausal women (age=57.1 ± 4.6 yr, weight=85.4 ± 15.4 kg and BMI=32.8 ± 4.5 kg/m(2)) were genotyped for TaqIA (n=127) by using PCR-RFLP analysis and categorized as possessing at least one copy of the A1 allele (A1(+)) or no copy (A1(-)). Women were randomized into two groups, caloric restriction (CR) and caloric restriction+resistance training (CRRT) and in this study were further classified as follows: A1(+)CR, A1(+)CRRT, A1-(-)CR and (-)A1(-)CRRT. Body composition, total daily EE, physical activity EE, Resting EE (REE), and energy intake were obtained at baseline and post-intervention using DXA, doubly-labeled water, indirect calorimetry, and 3-day dietary records, respectively. Results: Overall, all of the anthropometric variables and REE significantly decreased post-intervention (p<0.001). Women in the CRRT group lost significantly more fat mass (FM) than the CR women (p<0.05). There were significant time by group by allele interactions for attenuated body weight (BW), BMI, and FM loss for A1(+) (vs. A1(-)) in CRRT (p<0.05) and for increased % carbohydrate intake (p<0.01). Conclusion: TaqIA genotype was associated with body weight loss post-intervention; more specifically, carriers of the A1 allele lost significantly less BW and FM than the A1(-) and had increased carbohydrate intake in the CRRT group.
    Appetite 09/2012; 60(1). DOI:10.1016/j.appet.2012.09.010 · 2.69 Impact Factor
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    • "It has been demonstrated that olanzapine administration increased acute intake during a test meal in healthy volunteers (Roerig, et al., 2005) and self-reported daily intake in patients (Eder, et al., 2001; Gothelf, et al., 2002). Roerig, et al. (2005) also reported that acute hyperphagia following olanzapine was a consequence of heightened hunger – as indicated by changes from pre-meal subjective rating scale values. "
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    ABSTRACT: Olanzapine is a novel antipsychotic drug known to induce clinically significant weight gain. Although the cause of such weight gain is not fully known, drug-induced changes in appetite and food intake are likely to play a significant role together with other possible mechanisms enhancing weight and/or adiposity. We assessed acute drug effects on 1 hour intake and behavioural expression in female rats. Low doses of olanzapine (0.5 and 1 mg/kg) enhanced acute mash intake. Marked drug effects were seen on a number of behaviours following olanzapine over a range of doses. These effects included dose-related reductions in activity and exploratory behaviours and associated substantial dose-related increases in resting behaviour. Behavioural data were also used to plot drug effects over time, including behavioural satiety sequence (BSS) profiles, to evaluate whether olanzapine's hyperphagic effects might be a consequence of altered satiety development. BSS profiles reflected enhanced eating behaviour at low doses (0.5 and 1 mg/kg) but showed dose-related increases in resting, indicative of drug-induced sedation, which meant that it was impossible to fully discern olanzapine's effects on satiety. Acute olanzapine induces both hyperphagia and sedation, both of which may promote weight gain and adiposity, but which interact competitively.
    Journal of Psychopharmacology 04/2009; 24(7):1069-78. DOI:10.1177/0269881109102543 · 3.59 Impact Factor
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