Effects of Olanzapine and Haloperidol on the Metabolic Status of Healthy Men

Vidarsdottir, Solrun; Weenen, J. E. de Leeuw van; Frölich, Marijke; Roelfsema, Ferdinand; Romijn, Johannes A.; Pijl, Hanno

doi:10.1210/jc.2008-1815

Cited by 81 publications

(72 citation statements)

References 37 publications

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“…In rodent models of antipsychotic-induced glucose dysregulation, increased HGP is arguably the most commonly observed perturbation; however, whether or not this is the case in humans is unclear. Of the currently published studies in normalweight healthy volunteers treated with short-term (1-10 days) Ola (Sacher et al 2008, Vidarsdottir et al 2010a,b, Albaugh et al 2011b, Teff et al 2013, two employed the HIEC and separately assessed peripheral and hepatic insulin sensitivity, and both suggested impairments in glucose uptake, but failed to note increases in glucose production (Vidarsdottir et al 2010a, Teff et al 2013. Although these findings require replication, they suggest that if peripheral insulin sensitivity is indeed most prominently impacted by APs in humans, use of Met for patients on antipsychotic medications who develop diabetes is open to question.…”

Section: Discussionmentioning

confidence: 99%

“…However, their use is also associated with significant concerns in terms of metabolic side effects; high rates of metabolic syndrome, dyslipidemias, weight gain and glucose dysmetabolism have been reported (Goff et al(Pi-Sunyer 1993), there is growing evidence, both clinical and preclinical, indicating increased liability for glucose dysregulation independent of illness-related factors or weight increases (Ader et al 2005, Houseknecht et al 2007, Chintoh et al 2009, Vidarsdottir et al 2010a, Teff et al 2013, Hahn et al 2014. In this regard, our own work from preclinical rodent models consistently supports pronounced, direct effects on insulin sensitivity (peripheral and hepatic) following acute dosing of specific AP agents (e.g., risperidone, olanzapine (Ola) or clozapine) (Chintoh et al 2008(Chintoh et al , 2009.…”

Section: Introductionmentioning

confidence: 99%

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Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

Remington

Teo

Wilson

et al. 2015

Journal of Endocrinology

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Antipsychotics (APs) are linked to diabetes, even without weight gain. Whether anti-diabetic drugs are efficacious in reversing the direct effects of APs on glucose pathways is largely undetermined. We tested two metformin (Met) doses to prevent impairments seen following a dose of olanzapine (Ola) (3 mg/kg); glucokinetics were measured using the hyperinsulinemic-euglycemic clamp (HIEC). Met (150 mg/kg; nZ13, or 400 mg/kg; nZ11) or vehicle (Veh) (nZ11) was administered through gavage preceding an overnight fast, followed by a second dose prior to the HIEC. Eleven additional animals were gavaged with Veh and received a Veh injection during the HIEC (Veh/Veh); all others received Ola. Basal glucose was similar across treatment groups. The Met 400 group had significantly greater glucose appearance (R a ) in the basal period (i.e., before Ola, or hyperinsulinemia) vs other groups. During hyperinsulinemia, glucose infusion rate (GINF) to maintain euglycemia (reflective of whole-body insulin sensitivity) was higher in Veh/Veh vs other groups. Met 150/Ola animals demonstrated increased GINF relative to Veh/Ola during early time points of the HIEC. Glucose utilization during hyperinsulinemia, relative to basal conditions, was significantly higher in Veh/Veh vs other groups. The change in hepatic glucose production (HGP) from basal to hyperinsulinemia demonstrated significantly greater decreases in Veh/Veh and Met 150/Ola groups vs Veh/Ola. Given the increase in basal R a with Met 400, we measured serum lactate (substrate for HGP), finding increased levels in Met 400 vs Veh and Met 150. In conclusion, Met attenuates hepatic insulin resistance observed with acute Ola administration, but fails to improve peripheral insulin resistance. Use of supra-therapeutic doses of Met may mask metabolic benefits by increasing lactate.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

Remington

Teo

Wilson

et al. 2015

Journal of Endocrinology

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“…[10][11][12][13][14] Similarly, healthy humans who had been administered 1-9 days of olanzapine (and interestingly enough also aripiprazole -an agent considered to be less metabolically active) showed perturbations in glucose homeostasis before weight change. [15][16][17] This finding indicates that antipsychotics can directly affect glucose regulation separately from and in addition to their effects on weight gain.…”

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confidence: 85%

In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact

Kowalchuk¹,

Teo²,

Wilson³

et al. 2017

JPN

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“…Specifically SGAs are reported to induce acutely (<3 h) hyperglycemia in mice, whereas FGAs do not [46] - this effect could be mediated through an increased release of glucagon. As a matter of fact, in healthy men treated for 8 days with 10 mg/day of olanzapine, plasma concentrations of glucagon and prolactin increased, while treatment with haloperidol (3 mg/day) produced only an increase in prolactin [47]. Moreover, short-term treatment with olanzapine blunted the insulin-induced decline of plasma free fatty acids and triglyceride concentrations and hampered insulin action on glucose disposal in healthy men, whereas the effects of haloperidol were less clear [48].…”

Section: Discussionmentioning

confidence: 99%

Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients

Fabrazzo¹,

Monteleone²,

Prisco³

et al. 2015

Neuropsychobiology

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The effects of olanzapine and haloperidol on metabolic parameters in bipolar patients have been evaluated much less comprehensively than in schizophrenic patients. Therefore, in this study, medical records of 343 schizophrenic and bipolar patients treated with haloperidol or olanzapine for 1 year were retrospectively reviewed and metabolic outcomes were evaluated. After 12 months of follow-up, 25.9% of patients showed ≥3 metabolic abnormalities with a point prevalence of 27.2% in the bipolar and 24.9% in the schizophrenic group: 22.0% of the schizophrenic patients treated with haloperidol and 29.8% of those treated with olanzapine achieved ≥3 metabolic alterations; in bipolar patients, these percentages were 15.8% of those treated with haloperidol and 37.8% of those treated with olanzapine (p < 0.0001). Significant changes were reported over time in fasting glucose, triglycerides and cholesterol blood levels, systolic and diastolic blood pressure, body weight, and BMI. Overall, a significant number of schizophrenic and bipolar patients treated with olanzapine showed ≥3 metabolic alterations in the first month of treatment when compared to those treated with haloperidol. Moreover, the number of olanzapine-treated patients developing metabolic changes in the first month was significantly higher in both diagnostic groups when compared to those who reached metabolic abnormal values in the subsequent 11 months. These data suggest that both antipsychotics could increase the metabolic risk in schizophrenic and bipolar patients with a higher prevalence in olanzapine-treated patients. On the other hand, olanzapine-treated patients seem to achieve metabolic abnormalities faster than haloperidol-treated subjects in both diagnostic groups.

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Effects of Olanzapine and Haloperidol on the Metabolic Status of Healthy Men

Cited by 81 publications

References 37 publications

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact

Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients

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