Metabolic Risk with Second-Generation Antipsychotic Treatment: A Double-Blind Randomized 8-Week Trial of Risperidone and Olanzapine

Kelly, Deanna L.; Conley, Robert R.; Love, Raymond C.; Morrison, John A.; McMahon, Robert P.

doi:10.1080/10401230802017050

Cited by 22 publications

(18 citation statements)

References 26 publications

(31 reference statements)

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“…No significant difference in body mass index or weight change was observed between ENR-RIS and ENR-OLZ groups. The greater increases in triglycerides and greater decreases in prolactin observed in olanzapine-treated patients compared with risperidonetreated patients are consistent with previous findings for triglycerides (Hardy et al, 2006;Kelly et al, 2008;Meyer et al, 2008); and prolactin (Kinon et al, 2006;Konarzewska et al, 2009), but not consistent with the previously observed changes in body mass index and/or weight (Kelly et al, 2008). Somewhat surprising, though, was the observed difference in the development of treatment-emergent dyskinesia reported in nine ENRs maintained on risperidone (5.2%) compared with 1 ENR switched to olanzapine (0.6%).…”

Section: Discussionsupporting

confidence: 90%

Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

Kinon

Chen

Ascher-Svanum

et al. 2009

Neuropsychopharmacol

165

168

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Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether 'switching' early non-responders to another antipsychotic is a better strategy than 'staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as X20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2-6 mg/day or switch to olanzapine 10-20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; po001). Early response/nonresponse was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p ¼ 0.020) and in depressive symptoms (end point; p ¼ 0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatmentemergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a 'switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients.

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Section: Discussionsupporting

confidence: 90%

Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

Kinon

Chen

Ascher-Svanum

et al. 2009

Neuropsychopharmacol

165

168

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“…On the other hand, RPD did not induce an increase in food intake and body weight in both estrogen-untreated and -treated rats. This was in keeping with previous reports which revealed that RPD had a less harmful effect with regard to increases in body fats compared to OZP [9,14] . These discrepancies in the effects that the drugs produced may result from the different antagonistic actions of 5-HT2 serotonin receptors and D 2 dopamine receptors.…”

Section: Discussionsupporting

confidence: 81%

“…OZP has been reported to impair energy and glucose metabolism in nondiabetic rats and humans, but RPD does not seem to affect it [9,14] . However, the mechanism(s) by which these effects were produced have not been clearly outlined.…”

Section: Introductionmentioning

confidence: 99%

“…However, the mechanism(s) by which these effects were produced have not been clearly outlined. In addition, most studies have been performed in lean or obese nondiabetic or obese diabetic animals, and these rats have glucose intolerance, dyslipidemia and hyperinsulinemia in OZP treatment, but for them RPD is less detrimental [3,4,9,14] . Therefore, it is necessary to investigate energy and glucose metabolism in nonobese diabetic rats.…”

Section: Introductionmentioning

confidence: 99%

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Estrogen Replacement Reverses Olanzapine-Induced Weight Gain and Hepatic Insulin Resistance in Ovariectomized Diabetic Rats

Park

Hong²,

Ahn³

et al. 2010

Neuropsychobiology

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Objectives: We investigated whether estrogen replacement modulated energy and glucose metabolic changes induced by olanzapine (OZP) and risperidone (RPD) in 90% pancreatectomized diabetic rats, some of whom had also been ovariectomized (OVX) and some of whom had not (sham). Methods: OVX diabetic rats were subcutaneously injected with estrogen replacement (17β-estradiol, 30 µg/kg/day) or a vehicle. Each group was divided into 3 subgroups, and each subgroup was orally either given a placebo, RPD (0.5 mg/kg body weight/day) or OZP (2 mg/kg body weight/day) for 8 weeks. Sham rats were also divided into 3 subgroups and given drugs in the same manner as the OVX rats were. All rats were fed high-fat diets. Results: OZP increased body weight and epididymal fat pads more than the control (vehicle) in sham and OVX rats. Increased body weight in OZP-treated sham and OVX rats was due to the increment in food intake, which was associated with potentiating the phosphorylation of hypothalamic adenosine-monophosphate-activated protein kinase. At euglycemic hyperinsulinemic clamping, OZP decreased glucose infusion rates and increased hepatic glucose output in OVX diabetic rats. In sham rats, OZP increased hepatic glucose output but not as much as in OVX rats. Hepatic insulin signaling and glucose sensing were attenuated in OZP-treated OVX rats, and the attenuation increased hepatic phosphoenolpyruvate carboxykinase expression to induce gluconeogenesis. These negative and harmful effects noted among OZP-treated OVX rats were reversed by estrogen replacement treatment. However, RPD did not alter body weight and peripheral insulin sensitivity in sham and OVX rats. Conclusions: OZP treatment should be avoided when treating diabetic and schizophrenic women, especially those in their postmenopausal period.

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“…Lo que si queda claro es que los cambios metabólicos aparecen de forma temprana 131 , siendo necesaria una atención clínica desde el inicio del tratamiento con antipsicóticos.…”

Section: Control Del Riesgo Metabólico Y Cardiovascular En Los Pacienunclassified

Factores determinantes del riesgo metabólico en el tratamiento con antipsicóticos atípicos

Pato¹,

Rodríguez²,

Valverde³

2016

Psiquiatría Biológica

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Desde hace años se ha constatado que la esquizofrenia y otros trastornos psicóticos se asocian a elevadas tasas de morbimortalidad. Las causas de este incremento van desde las asociadas al uso de tratamientos específicos para esta enfermedad como a factores de salud relacionados con dicho proceso.Las principales causas de muerte en personas con enfermedad mental grave son similares a las observadas en la población general. Así, en la población general, la enfermedad cardiovascular es la principal causa de mortalidad y dicha mortalidad se ha reducido en los últimos años debido a las mejoras tratamientos y a las iniciativas de salud pública. Sin embargo, la enfermedad cardiovascular aún es alta en personas con enfermedad mental grave y en ellas no se ha visto esta reducción 1 .Los pacientes con esquizofrenia tienen una esperanza de vida un 20% menor que la población general, calculándose que mueren una media de 25 años antes 2 . Se calcula un riesgo relativo de 7,5 veces superior a la población general para la mortalidad por causas no naturales, como suicidio o muerte accidental (40% de las muertes prematuras en estos pacientes); y de 2,41 veces para la mortalidad por causas naturales, especialmente enfermedades cardiovasculares, infecciosas, respiratorias, y endocrinas 3 (60% de las muertes prematuras en estos pacientes) calculándose una mortalidad general 2-3 veces superior que en la población general 4 .En estudios que abordan específicamente las causas de muerte en la esquizofrenia frente a la población general establecen las siguientes cifras: un riesgo 2,7 veces mayor en la diabetes, un riesgo 2,3 veces mayor para enfermedades cardiovasculares, un riesgo de 3,2 veces mayor para las enfermedades respiratorias y de un 3,4 para enfermedades infecciosas 5 .En general, la mayor mortalidad cardiovascular asociada a la esquizofrenia, la depresión unipolar y el trastorno bipolar se atribuye a un riesgo relativo a presentar factores de riesgo modificables de enfermedad cardiovascular de 1 a 5 veces superior al del resto de la población 6 , tal y como se aprecia en la tabla 1.

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Metabolic Risk with Second-Generation Antipsychotic Treatment: A Double-Blind Randomized 8-Week Trial of Risperidone and Olanzapine

Abstract: The fact that significant metabolic changes occurred (both positive and negative) in eight weeks is important to clinical care. Monitoring for metabolic changes may be important within the first eight weeks of treatment, as changes can be determined very early in antipsychotic treatment.

Cited by 22 publications

References 26 publications

Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

Estrogen Replacement Reverses Olanzapine-Induced Weight Gain and Hepatic Insulin Resistance in Ovariectomized Diabetic Rats

Factores determinantes del riesgo metabólico en el tratamiento con antipsicóticos atípicos

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