Finally, some insight on how antipsychotics cause weight gain and metabolic syndrome
Second Generation Antipsychotics (such as olanzapine, quetiapine, etc) are a mixed bag. On one hand, some physicians view them as a god-send for the treatment of schizophrenia, bipolar disorder, and even as augmentation strategies for antidepressants. Quite a few studies show that they can upregulate neurogenesis in key areas of the brain similar to antidepressants. Their main selling point over the older antipsychotic drugs is a lower prevalence of extrapyrmidal side-effects (parkinson symptoms). But the big issue with these drugs is their ability to cause massive weight gain and insulin resistance. And in our overweight society of fast food, drugs that cause weight gain is possibly the last thing we need. This can be a particular draw back for mental health patients who probably already have issues with self-esteem (and overall health).
The following abstract provides some ideas on how these drugs might cause such weight gain. It looks like they directly affect fat cells, decreasing fat breakdown and favoring fat cell growth in addition to making the fat cells insulin resistant:
Neuropsychopharmacology. 2006 Jun 28; [Epub ahead of print]
Atypical Antipsychotic Drugs Directly Impair Insulin Action in Adipocytes: Effects on Glucose Transport, Lipogenesis, and Antilipolysis.
Vestri HS, Maianu L, Moellering DR, Garvey WT.
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
Treatment with second-generation antipsychotics (SGAs) has been associated with weight gain and the development of diabetes mellitus, although the mechanisms are unknown. We tested the hypothesis that SGAs exert direct cellular effects on insulin action and substrate metabolism in adipocytes. We utilized two cultured cell models including 3T3-L1 adipocytes and primary cultured rat adipocytes, and tested for effects of SGAs risperidone (RISP), clozapine (CLZ), olanzapine (OLZ), and quetiapine (QUE), together with conventional antipsychotic drugs butyrophenone (BUTY), and trifluoperazine (TFP), over a wide concentration range from 1 to 500 muM. The effects of antipsychotic drugs on basal and insulin-stimulated rates of glucose transport were studied at 3 h, 15 h, and 3 days. Both CLZ and OLZ (but not RISP) at doses as low as 5 muM were able to significantly decrease the maximal insulin-stimulated glucose transport rate by approximately 40% in 3T3-L1 cells, whereas CLZ and RISP reduced insulin-stimulated glucose transport rates in primary cultured rat adipocytes by approximately 50-70%. Conventional drugs (BUTY and TFP) did not affect glucose transport rates. Regarding intracellular glucose metabolism, both SGAs (OLZ, QUE, RISP) and conventional drugs (BUTY and TFP) increased basal and/or insulin-stimulated glucose oxidation rates, whereas rates of lipogenesis were increased by CLZ, OLZ, QUE, and BUTY. Finally, rates of lipolysis in response to isoproterenol were reduced by the SGAs (CLZ, OLZ, QUE, RISP), but not by BUTY or TFP. These experiments demonstrate that antipsychotic drugs can differentially affect insulin action and metabolism through direct cellular effects in adipocytes. However, only SGAs were able to impair the insulin-responsive glucose transport system and to impair lipolysis in adipocytes. Thus, SGAs directly induce insulin resistance and alter lipogenesis and lipolysis in favor of progressive lipid accumulation and adipocyte enlargement. These effects of SGAs on adipocytes could explain, in part, the association of SGAs with weight gain and diabetes.Neuropsychopharmacology advance online publication, 28 June 2006; doi:10.1038/sj.npp.1301142.
PMID: 16823387 [PubMed - as supplied by publisher]
The following abstract provides some ideas on how these drugs might cause such weight gain. It looks like they directly affect fat cells, decreasing fat breakdown and favoring fat cell growth in addition to making the fat cells insulin resistant:
Neuropsychopharmacology. 2006 Jun 28; [Epub ahead of print]
Atypical Antipsychotic Drugs Directly Impair Insulin Action in Adipocytes: Effects on Glucose Transport, Lipogenesis, and Antilipolysis.
Vestri HS, Maianu L, Moellering DR, Garvey WT.
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
Treatment with second-generation antipsychotics (SGAs) has been associated with weight gain and the development of diabetes mellitus, although the mechanisms are unknown. We tested the hypothesis that SGAs exert direct cellular effects on insulin action and substrate metabolism in adipocytes. We utilized two cultured cell models including 3T3-L1 adipocytes and primary cultured rat adipocytes, and tested for effects of SGAs risperidone (RISP), clozapine (CLZ), olanzapine (OLZ), and quetiapine (QUE), together with conventional antipsychotic drugs butyrophenone (BUTY), and trifluoperazine (TFP), over a wide concentration range from 1 to 500 muM. The effects of antipsychotic drugs on basal and insulin-stimulated rates of glucose transport were studied at 3 h, 15 h, and 3 days. Both CLZ and OLZ (but not RISP) at doses as low as 5 muM were able to significantly decrease the maximal insulin-stimulated glucose transport rate by approximately 40% in 3T3-L1 cells, whereas CLZ and RISP reduced insulin-stimulated glucose transport rates in primary cultured rat adipocytes by approximately 50-70%. Conventional drugs (BUTY and TFP) did not affect glucose transport rates. Regarding intracellular glucose metabolism, both SGAs (OLZ, QUE, RISP) and conventional drugs (BUTY and TFP) increased basal and/or insulin-stimulated glucose oxidation rates, whereas rates of lipogenesis were increased by CLZ, OLZ, QUE, and BUTY. Finally, rates of lipolysis in response to isoproterenol were reduced by the SGAs (CLZ, OLZ, QUE, RISP), but not by BUTY or TFP. These experiments demonstrate that antipsychotic drugs can differentially affect insulin action and metabolism through direct cellular effects in adipocytes. However, only SGAs were able to impair the insulin-responsive glucose transport system and to impair lipolysis in adipocytes. Thus, SGAs directly induce insulin resistance and alter lipogenesis and lipolysis in favor of progressive lipid accumulation and adipocyte enlargement. These effects of SGAs on adipocytes could explain, in part, the association of SGAs with weight gain and diabetes.Neuropsychopharmacology advance online publication, 28 June 2006; doi:10.1038/sj.npp.1301142.
PMID: 16823387 [PubMed - as supplied by publisher]
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