Body Weight Gain after Administration of Antipsychotic Drugs: Correlation with Leptin, Insulin and Reproductive hormones

Abstract

Excessive body weight gain, hyperprolactinemia and low gonadal steroid serum levels are often observed during chronic administration of antipsychotic drugs (AP). Clinical and experimental findings suggest that leptin, the peptidic hormone involved in long-term body weight regulation, and reproductive hormones are interrelated. Therefore, we assessed circulating leptin levels in healthy, lean women (n = 12) and men (n = 7) before and after short-term administration of the AP sulpiride (SUL, 200 mg/day). In addition, we studied psychotic obese (n = 9) and lean women (n = 13) under chronic treatment with diverse AP. No significant weight changes were observed after SUL administration in healthy women--initial weight: 54.9+/-2.6 Kg; final weight: 55.04+/-2.6, NS. Leptin levels did not change either: 11.9+/-1.5 ng/ml. vs. 10.6+/-1.3, NS. By contrast, a small, but significant weight gain was found in SUL-treated men--60.6+/-1.9 Kg. vs. 61.3+/-2.1, p = 0.004. Leptin and insulin levels were significantly higher after SUL administration--leptin: 2.77+/-0.22 ng/ml. vs. 13.9+/-2.5, p=0.035; insulin: 3.59+/-0.17 mIU/ml vs. 8.81+/-0.81, p = 0.0001. In these subjects, leptin levels positively correlated with body weight change (p = 0.006), and serum prolactin change (p = 0.001). Obese psychotic women (Body Mass Index, BMI, Kg/m2 = 31.5+/-1.03) displayed higher leptin levels than non-obese psychotic women (BMI = 25.5+/-0.52): 26.8+/-4.8, vs. 12.8+/-3.4 ng/ml, p = 0.006. In these women, a significant positive correlation was found between leptin levels and BMI (p = 0.0001), and between leptin and basal insulin levels (p = 0.001). These results show that the expected circulating leptin elevation which is observed when body weight raises, is preserved in people treated with AP drugs.

Ghrelin and leptin levels in relation to puberty and reproductive function in patients with beta-thalassemia

“…34 A positive correlation between leptin and BMI was detected only in the female control group, a finding in agreement with previous reports. 35 Since the BMI of the patients is lower than that of the gender matched control group, it could be concluded that adipose tissue is unable to maintain adequate leptin production when a higher leptin secretion is required, suggesting that the inappropriately low leptin secretion or decreased leptin/ghrelin ratio could contribute to the relevant pathology, namely the irregular menses or amenorrhea of the thalassemic females. Obviously, more data are needed for a valid interpretation of our findings, which may have relevance to other forms of irregular menses or amenorrhea.…”

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

“…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). One cross-sectional study in bipolar subjects also found no correlation between any glucose or lipid parameter and leptin levels (Gergerlioglu et al, 2006), although a small number reported significant correlations between leptin and serum insulin (Baptista et al, 2000;Melkersson et al, 2000;Melkersson and Hulting, 2001), glucose (Wang et al, 2006) and serum triglycerides (Atmaca et al, 2003c); however, most of the authors reporting significant correlations did not control for BMI.…”

“…Numerous subsequent prospective trials of olanzapine-treated patients (Eder et al, 2001;Graham et al, 2005b;Ebenbichler et al, 2005;Murashita et al, 2005;Hosojima et al, 2006) and clozapine-treated patients (Monteleone et al, 2002;Kivircik et al, 2003;Sporn et al, 2005;Theisen et al, 2005) confirmed the association between use of these medications, weight gain, and increased serum leptin levels. For agents with less weight gain liability, such as high potency typicals (Hagg et al, 2001;Atmaca et al, 2003a;Atmaca et al, 2003c), sulpiride (Baptista et al, 2000), quetiapine (Atmaca et al, 2003c), or risperidone (Fitzgerald et al, 2003;McIntyre et al, 2003;Martin et al, 2004;Chiu et al, 2006), comparative trials noted modest weight gain and leptin changes, while olanzapine and clozapine exposed subjects experienced marked increases in adiposity, weight and serum leptin. A few prospective trials which examined the effect of pharmacological weight-modifying strategies using adjunctive amantadine (Graham et al, 2005a) or nizatidine (Atmaca et al, 2003b;Atmaca et al, 2004) found positive effects of the adjunctive medication, with proportional differences in leptin levels compared to those treated with antipsychotic alone.…”

“…When studied prospectively, this gender discrepancy was gradually effaced as men demonstrated greater increases in serum leptin during several trials (Baptista et al, 2000;Hagg et al, 2001;Zhang et al, 2003). Data from for one long-term clozapinetreated study found that leptin changes were independent of gender and proportional to weight gain (Monteleone et al, 2002), but other analyses which examined both weight and fat depots still found significant effects of gender (Zhang et al, 2004).…”

Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine

“…On the other hand, drugs that block dopamine D2 receptors increase appetite and result in significant weight gain. Healthy subjects treated with antipsychotic drugs (dopamine antagonists) gain weight (3). Furthermore, of particular interest is the recent report that dopamine deficiency in obese individuals may perpetuate pathological eating and strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals (4).…”