Endocrine and Metabolic Abnormalities Involved in Obesity [nl]Associated with Typical Antipsychotic Drug Administration

Abstract

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.

Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin

“…These studies indicate conclusively that, when matched appropriately with nonpsychiatric subjects, patients with schizophrenia do not exhibit greater than expected serum leptin levels regardless of antipsychotic drug exposure (Baptista et al, 2001;Eder et al, 2001;Herran et al, 2001;Hagg et al, 2001;Zhang et al, 2003;Arranz et al, 2004;Sporn et al, 2005;Haupt et al, 2005;Gergerlioglu et al, 2006;Atmaca et al, 2007). The one controlled comparative study of medication-treated bipolar patients vs. matched controls also reported no significant difference in leptin levels between the psychiatric patients and their peers (Gergerlioglu et al, 2006).…”

“…Several antipsychotic studies measured metabolic outcomes along with serum leptin levels, but did not specifically calculate correlation coefficients between leptin and other parameters (Baptista et al, 2001;Eder et al, 2001;Atmaca et al, 2003a;Melkersson and Dahl, 2003;Graham et al, 2005a;Graham et al, 2005b;Smith et al, 2005;Sporn et al, 2005;Chiu et al, 2006;Hosojima et al, 2006;Atmaca et al, 2007). Nonetheless, in many instances leptin levels increased significantly without significant changes in serum insulin, other glycemic or lipid measures (Zhang et al, 2004;Murashita et al, 2005;Sporn et al, 2005;Chiu et al, 2006;Hosojima et al, 2006;Atmaca et al, 2007).…”

Metabolic Dysregulation With Atypical Antipsychotics Occurs in the Absence of Underlying Disease A Placebo-Controlled Study of Olanzapine and Risperidone in Dogs

“…Moreover, this study used a minimal (3-day) washout period before OLZ treatment for the large number of subjects with prior treatment history with other antipsychotics. Induction of central obesity by atypical antipsychotics has also been inferred from cross-sectional studies (44,45) reporting waist-to-hip ratios. Clearly, the present studies are unique in that they provide the first accurate measures of adiposity during antipsychotic treatment and support the idea that adiposity may be increased considerably more than is reflected in body weight alone.…”

A comparative study of the effects of risperidone and olanzapine on metabolic parameters of schizophrenic patients

“…This fall in HDL levels after these drugs is in concordance with majority of the studies. [27][28][29] When comparing the number of subjects fulfilling the criteria for raised HDL-C (as per MS-IDF) criteria, it was found that in olanzapine group, 3 subjects met the criteria before intervention and the number increased to 10. On the other hand in risperidone group, the number of subjects fulfilling the raised HDL-C criteria increased from 4 to 7.…”