title: Metabolic syndrome and obesity among users of second generation antipsychotics: A global challenge for modern psychopharmacology.
abstract: Second generation antipsychotics (SGAs), such as clozapine, olanzapine, risperidone and quetiapine, are among the most effective therapies to stabilize symptoms schizophrenia (SZ) spectrum disorders. In fact, clozapine, olanzapine and risperidone have improved the quality of life of billions SZ patients worldwide. Based on the broad spectrum of efficacy and low risk of extrapyramidal symptoms displayed by SGAs, some regulatory agencies approved the use of SGAs in non-schizophrenic adults, children and adolescents suffering from a range of neuropsychiatric disorders. However, increasing number of reports have shown that SGAs are strongly associated with accelerated weight gain, insulin resistance, diabetes, dyslipidemia, and increased cardiovascular risk. These metabolic alterations can develop in as short as six months after the initiation of pharmacotherapy, which is now a controversial fact in public disclosure. Although the percentage of schizophrenic patients, the main target group of SGAs, is estimated in only 1% of the population, during the past ten years there was an exponential increase in the number of SGAs users, including millions of non-SZ patients. The scientific bases of SGAs metabolic side effects are not yet elucidated, but the evidence shows that the activation of transcriptional factor SRBP1c, the D1/D2 dopamine, GABA2 and 5HT neurotransmitions are implicated in the SGAs cardiovascular toxicity. Polypharmacological interventions are either non- or modestly effective in maintaining low cardiovascular risk in SGAs users. In this review we critically discuss the clinical and molecular evidence on metabolic alterations induced by SGAs, the evidence on the efficacy of classical antidiabetic drugs and the emerging concept of antidiabetic polyphenols as potential coadjutants in SGA-induced metabolic disorders.
authors.affiliation: Facultad de Ciencias de la Salud, Universidad Arturo Prat, Av. Arturo Prat N°2120, Iquique, Chile. Electronic address: leonelrojoc@gmail.com.
authors.forename: Leonel E
authors.initials: LE
authors.lastname: Rojo
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Psychiatry, Clinical Hospital of the University of Chile, Chile.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Gaspar
authors.affiliation: Department of Psychiatry, Clinical Hospital of the University of Chile, Chile.
authors.forename: H
authors.initials: H
authors.lastname: Silva
authors.affiliation: Department of Psychiatry, Clinical Hospital of the University of Chile, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Risco
authors.affiliation: Facultad de Ciencias de la Salud, Universidad Arturo Prat, Av. Arturo Prat N°2120, Iquique, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Arena
authors.affiliation: Facultad de Ciencias de la Salud, Universidad Arturo Prat, Av. Arturo Prat N°2120, Iquique, Chile.
authors.forename: Karen
authors.initials: K
authors.lastname: Cubillos-Robles
authors.affiliation: Facultad de Ciencias de la Salud, Universidad Arturo Prat, Av. Arturo Prat N°2120, Iquique, Chile.
authors.forename: Belen
authors.initials: B
authors.lastname: Jara
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D002648:Child; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D008954:Models, Biological; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D059808:Polyphenols / Q000627:therapeutic use; D011600:Psychopharmacology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D007004:Hypoglycemic Agents; D059808:Polyphenols
keywords: Diabetes; Insulin resistance; Metabolic syndrome; Obesity; Schizophrenia; Second generation antipsychotics