Decrease of energy expenditure causes weight increase in olanzapine treatment - a case study

The aim of this study was to evaluate the mechanisms underlying weight gain induced by the atypical antipsychotic, olanzapine. We performed euglycemic, hyperinsulinemic clamp combined with indirect calorimetry on a 48-year-old male with antisocial personality disorder, alcohol dependence and paranoid ideation before and after one month of olanzapine (10 - 15 mg/day) therapy. The patient gave his informed, written consent for this study. The results were a weight gain of 6 kg and a decrease in both basal (from 1673 to 1613 kcal/24 h) and 3-hour (from 22.8 to 20.2 cal/kg fat free mass/min) energy expenditure. Serum thyroid hormone and high-density lipoprotein cholesterol levels decreased, and the triglyceride and low-density lipoprotein cholesterol levels increased. Insulin sensitivity did not change. We conclude that decreased basal energy expenditure may contribute to weight gain in olanzapine treatment.     

抗精神病药对代谢的影响比较

目的:探讨抗精神病药对体质量、血糖、血脂、胰岛素、瘦素的影响。方法:首发住院精神分裂症患者94例随机分为3组,分别服用氯氮平、利培酮、奥氮平治疗,于治疗前和治疗6周测定体质量、血清瘦素、胰岛素、胰岛素抗体、空腹血糖、糖化血红蛋白(HbA1c)、血清胆固醇(TC)及三酰甘油(TG)。结果:3组治疗前后BMI变化分别为(2.37±2.11)kg/m2、(1.32±1.77)kg/m2、(2.07±1.38)kg/m2(F=10.783,P=0.000)。治疗前3组糖化血红蛋白差异显著(F=16.412,P<0.001),初始血糖、初始TC、TG、胰岛素、瘦素水平差异无显著性(P>0.05)。治疗6周后,3组间血糖、初始TC、TG、胰岛素、瘦素水平均有显著性差异。结论:氯氮平对体质量、血糖、血脂、瘦素及胰岛素的影响大;奥氮平不良反应较小,对体质量、血脂、血浆瘦素水平影响较大;利培酮对各项代谢指标及体质量的影响较小。     

Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics

BACKGROUND: Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain. METHOD: The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002. RESULTS: Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups. CONCLUSION: Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.     

Association of olanzapine-induced weight gain with an increase in body fat

OBJECTIVE: The goal of this study was to explore the pathophysiology of weight gain during treatment with olanzapine for schizophrenia. METHOD: The authors used a prospective, controlled, open study comparing body weight, body mass index, and related biological measures in mentally and physically healthy volunteers and olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin serum levels, body mass index, and body composition were assessed over an 8-week observation period. RESULTS: A significant increase in body weight, leptin serum levels, and percentage of body fat was seen in patients treated with olanzapine, but the drug-free comparison group did not show any significant changes. The weight gain during antipsychotic treatment with olanzapine was mainly attributable to an increase in body fat; patients' lean body mass did not change. CONCLUSIONS: In addition to the original finding that an increase in body fat is mainly responsible for olanzapine-induced weight gain, these findings confirm results obtained in other studies showing increases in body weight and serum leptin levels during treatment with second-generation antipsychotics.     

Olanzapine increases plasma ghrelin level in patients with schizophrenia

OBJECTIVE: Increased appetite and weight gain are frequently reported in treatment with olanzapine. However, the mechanism behind this appetite gain remains unclear. Ghrelin is a newly discovered appetite-stimulating peptide that has a role in the regulation of feeding behavior. Ghrelin is synthesized principally in the stomach, and the concentration of circulating ghrelin is negatively correlated with leptin and body fat mass. To elucidate the mechanism of appetite and weight gain during olanzapine treatment, we investigated the circulating ghrelin levels. METHODS: Seven patients with schizophrenia were examined before and after 6-month administration of olanzapine. The concentrations of circulating ghrelin, leptin, glucose and lipid metabolic parameters were measured. RESULTS: Body fat percentage (P=0.0121) and serum leptin (P=0.0284) were significantly increased after 6-month administration of olanzapine. Both plasma total ghrelin (P=0.0188) and active ghrelin levels (P=0.0057) were significantly increased. Six of the seven patients reported increased appetite during olanzapine treatment. Other glucose and lipid parameters were not altered significantly. CONCLUSIONS: Although, the leptin level and body fat percentage were significantly increased, the concentration of circulating ghrelin was also significantly increased. Olanzapine may directly act on the secretion of ghrelin and induce appetite, resulting in weight gain.     

Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses

BACKGROUND: The aim of this study was to investigate the influence of the antipsychotic agent olanzapine on glucose-insulin homeostasis to explain possible mechanisms behind olanzapine-associated weight gain. METHOD: Fourteen patients on treatment with olanzapine (all meeting DSM-IV criteria for schizophrenia or related psychoses) were studied. Fasting blood samples for glucose, insulin, the growth hormone (GH)-dependent insulin-like growth factor I, and the insulin-dependent insulin-like growth factor binding protein-1 (IGFBP-1) were analyzed, as well as GH, leptin, and blood lipid levels and the serum concentrations of olanzapine and its metabolite N-desmethylolanzapine. In addition, body mass index (BMI) was calculated. Moreover, weight change during olanzapine treatment was determined. RESULTS: Twelve of the 14 patients reported weight gain between 1 and 10 kg during a median olanzapine treatment time of 5 months, whereas data were not available for the other 2 patients. Eight patients (57%) had BMI above the normal limit. Eleven patients were normoglycemic, and 3 showed increased blood glucose values. Most patients (10/14; 71%) had elevated insulin levels (i.e., above the normal limit). Accordingly, the median value of IGFBP-1 was significantly lower for the patients in comparison with healthy subjects. Moreover, 8 (57%) of 14 patients had hyperleptinemia, 62% (8/13) had hypertriglyceridemia, and 85% (11/13) hypercholesterolemia. Weight change correlated positively to blood glucose levels and inversely to the serum concentration level of N-desmethylolanzapine. Additionally, the levels of blood glucose, triglycerides, and cholesterol correlated inversely to the serum concentration of N-desmethylolanzapine. CONCLUSION: Olanzapine treatment was associated with weight gain and elevated levels of insulin, leptin, and blood lipids as well as insulin resistance, with 3 patients diagnosed to have diabetes mellitus. Both increased insulin secretion and hyprleptinemia may be mechanisms behind olanzapine-induced weight gain. Moreover, it is suggested that the metabolite N-desmethylolanzapine, but not olanzapine, has a normalizing effect on the metabolic abnormalities.     

Effects of chronic neuroleptic treatments on nutrient selection, body weight, and body composition in the male rat under dietary self-selection

New antipsychotic drugs often increase weight and produce metabolic disturbances in treated patients. However, the mechanisms by which neuroleptics induce these undesirable side effects in humans are not known. Studies have shown that antipsychotics can increase body weight in female but not in male rats. However, no studies investigated changes in macronutrient selection during chronic treatments with antipsychotics in male rats, and no studies investigated precisely body composition after such treatments. In the present work, we studied in male rats the effects of long-term administration of two neuroleptics: haloperidol, a classical neuroleptic which has a moderate effect on weight gain in humans, and olanzapine, an atypical neuroleptic which has a more important effect on weight gain. Treatments (both 1 mg/kg) were given orally for 6 weeks, and the animals were allowed to self-select food among carbohydrates, lipids and proteins. Food selection was measured throughout the study, and body composition was measured by dissection and weighing of the main organs and tissues. Circulating leptin, insulin and glucose were also assayed at the end of the study on blood collected at the time of carcass analysis. The results show that none of the neuroleptic treatments modified caloric intake, food selection, body weight, and body composition. Olanzapine produced a statistically non-significant increase in subcutaneous fat tissue. It is concluded that a 6-week olanzapine or haloperidol treatment in male rats under dietary macronutrient selection does not significantly affect energy regulation.     

抗精神病药治疗与体质量和血脂等的关系

目的：探讨引起住院精神分裂症患者体质量增加的相关因素。方法：首发住院精神分裂症患者72例分别于治疗前和治疗6周末测定体质量、血清瘦素、胰岛素、胰岛素抗体、糖化血红蛋白（HbA1c）、空腹血糖、血清胆固醇（T-CHO）及三酰甘油（TG）。结果：服抗精神病药后体质量有显著性增高（t=7．865，P=0．000）。体质量变化与服药种类（γ=-0．400，P〈0．01）等有关。结论：影响住院精神分裂症患者体质量变化最主要的3个因素为：服用精神药物种类、初始三酰甘油及瘦素变化量。     

Olanzapine induces insulin resistance: results from a prospective study

BACKGROUND: The aim of this study was to compare glucose metabolism in patients with schizophrenia receiving olanzapine with that in control subjects. METHOD: We conducted a prospective, controlled, open study comparing body weight, fat mass, and indices of insulin resistance/ sensitivity in 10 olanzapine-treated patients with ICD-10 schizophrenia (olanzapine dose range, 7.5-20 mg/day) with those of a group of 10 mentally and physically healthy volunteers. Weight, fat mass, and indices of insulin resistance/sensitivity were assessed over individual 8-week observation periods from November 1997 to October 1999. RESULTS: Fasting serum glucose and fasting serum insulin increased significantly in the olanzapine-treated patients (p =.008 for glucose and p =.006 for insulin). The homeostasis model assessment (HOMA) index for beta cell function did not change significantly in the olanzapine-treated patients, whereas the HOMA index for insulin resistance did increase (p =.006). In the control group, these parameters were stable. A significant increase in body weight (p =.001) and body fat (p =.004) was seen in patients treated with olanzapine, while the control group showed no significant changes. CONCLUSION: This study indicates that the disturbances in glucose homeostasis during antipsychotic treatment with olanzapine are mainly due to insulin resistance. However, beta cell function remains unaltered in olanzapine-treated patients. We conclude that treatment with some second-generation antipsychotic drugs may lead to insulin resistance.     

Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment

Although antipsychotics are established drugs in schizophrenia treatment, they are admittedly known to induce side effects favoring the onset of obesity and worsening its complications. Despite potential involvement of histamine receptor antagonism, or of other neurotransmitter systems, the mechanism by which antipsychotic drugs increase body weight is not elucidated. The aim of the present study was to investigate whether chronic antipsychotic treatments can directly alter the regulation of two main functions of white adipose tissue: lipolysis and glucose utilization. The influence of a classical antipsychotic (haloperidol) was compared to that of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (ziprasidone). Cell size, lipolytic capacity and glucose transport activity were determined in white adipocytes of rats subjected to 5-week oral treatment with these antipsychotics. Gene expression of adipocyte proteins involved in glucose transport or fat storage and mobilization, such as glucose transporters (GLUT1 and GLUT4), leptin, matrix metallo-proteinase-9 (MMP9), hormone-sensitive lipase (HSL) and fatty acid synthase (FAS) was also evaluated. Adipocytes from chronic olanzapine-treated rats exhibited decreased lipolytic activity, lowered HSL expression and increased FAS expression. These changes were concomitant to enlarged fat deposition and adipocyte size. Alterations were observed in adipocytes from olanzapine-treated rats whereas the other antipsychotics did not induce any notable disorder. Our results therefore show evidence of an effect of chronic antipsychotic treatment on rat adipocyte metabolism. Thus, impairment of fat cell lipolysis should be considered as a side effect of certain antipsychotics, leading, along with the already documented hyperphagia, to the excessive weight gain observed in patients under prolonged treatment..     

奥氮平诱导C57BL/6J 雄性小鼠能量失衡和糖代谢紊乱的机制

目的 观察奥氮平对雄性小鼠能量消耗和糖代谢的影响及可能机制.方法 将10只C57BL/6J雄性小鼠随机分为两组,分别奥氮平及其溶剂灌胃2周,观察小鼠摄食、体质量、空腹血糖、糖耐量和胰岛素耐量的变化,监测24 h能量代谢,并比较肝脏糖代谢相关基因的表达.结果 小鼠奥氮平给药后出现胰岛素抵抗和高血糖;白天能量消耗明显下降,呼吸商趋势性下降,氧化底物由葡萄糖向脂肪转移;肝内糖异生关键酶磷酸烯醇式丙酮酸羟激酶(PEPCK)和葡萄糖-6-磷酸酶(G-6-pase)的基因表达明显升高.结论 奥氮平诱导的高血糖可不依赖于摄食和体质量增加;奥氮平可直接诱导胰岛素抵抗并促进肝糖异生.     

Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine

OBJECTIVE: The authors studied weight gain mechanisms and energy balance in patients treated with olanzapine. METHOD: The body mass index of male schizophrenic adolescent inpatients treated with olanzapine (N=10) and of 10 matched patients treated with haloperidol (N=10) were measured at baseline and after 4 weeks of treatment. For the patients treated with olanzapine, caloric intake, resting energy expenditure, and physical activity (determined through accelerometry and heart rate monitoring) were assessed at baseline and after 4 weeks of treatment. RESULTS: Body mass index significantly increased in those treated with olanzapine but not in those given haloperidol. The increase in body mass index was due to an increase in caloric intake without change in diet composition. Olanzapine had no significant effect on resting energy expenditure. Daily energy expenditure was very low before and after treatment. CONCLUSIONS: Olanzapine-induced weight gain is associated with a general increase in caloric intake.     

Decreased levels of ghrelin, cortisol, and fasting blood sugar, but not n-octanoylated ghrelin, in Japanese schizophrenic inpatients treated with olanzapine

The mechanism by which chronic administration of olanzapine induces a marked weight gain in patients with schizophrenia remains unknown. We examined the influence of long-term treatment with olanzapine on plasma levels of hormones regulating food intake and energy homeostasis in schizophrenia. In this study, olanzapine was administered to 28 Japanese inpatients for 16 weeks after switching from typical antipsychotic drugs or risperidone. At endpoint, no significant changes in body weight or body mass index were found. There was a significant decrease in the plasma levels of ghrelin without any accompanying change in active, n-octanoylated ghrelin. Serum levels of leptin tended to be increased and a significant reduction in plasma cortisol levels was found. In addition, the levels of fasting blood sugar as well as free fatty acid were significantly decreased. Furthermore, we did not confirm any marked weight gain induced by chronic administration of olanzapine as previously reported. The reason for this discrepancy may be due to differences in subjects and treatment settings. Based on these findings, it is unlikely that the decrease in plasma ghrelin levels by chronic administration of olanzapine affects weight gain. Further studies examining the effect of chronic olanzapine administration on weight and energy homeostasis in inpatients are required.     

四种抗精神病药对糖代谢及脂代谢的不良影响

目的研究4种抗精神病药对糖代谢、脂代谢的不良影响。方法112例精神分裂症患者根据临床治疗需要分为氯氮平组（30例）、奥氮平组（24例）、利培酮组（29例）和舒必利组（29例），均治疗观察4周。每组患者于治疗前后测空腹血糖、甘油三酯、胆固醇、胰岛素、C肽，量身高、体质量、腰围、臀围，并计算体质量指数（BMI）及胰岛素抵抗指数（IR）。结果（1）治疗后4组患者的空腹胰岛素、C肽及IR均升高，与治疗前的差异有统计学意义（P〈0．05）；治疗后氯氮平组和奥氮平组患者的甘油三酯及胆固醇均明显高于治疗前（P〈0．05）。（2）治疗后BMI的升高程度为：氯氮平〉奥氮平〉舒必利〉利培酮，差异均有统计学意义（P〈0．05）。空腹胰岛素、C肽、甘油三酯、胆固醇及IR的升高程度为：氯氮平和奥氮平〉舒必利和利培酮，差异均有统计学意义（P〈0．05）。（3）氯氮平组、奥氮平组的甘油三酯及IR升高程度均为男性大于女性，胆固醇升高程度为女性大于男性；舒必利组的变化则相反。结论氯氮平和奥氮平对糖代谢及脂代谢的影响大于利培酮和舒必利，并存在性别差异。     

抗精神病药物治疗急性期体脂分布特征及其与血脂代谢相关性研究

目的　探讨抗精神病药物治疗急性期体脂分布特征及其与血脂代谢的关系。方法　对 4 6例入选患者采用自身配对设计 ,给予单一抗精神病药物 (APS)治疗 10周 ,检测患者治疗前后体重、体重指数 (BMI)和血脂 ,并采用结构核磁共振测定其中 4 0例患者治疗前后体脂指标 ,包括腹部皮下脂肪 (SUB)和内脏脂肪 (IAF)。结果　APS治疗前后患者体重指标差异有显著性 (P <0 0 5～P <0 0 0 0 1) ,体脂指标差异有显著性 (PSUB<0 0 5、PIAF<0 0 0 1) ,男性体脂指标变化值明显高于女性 ;血脂指标治疗前后差异有显著性 (P <0 0 1～P <0 0 0 0 1) ;治疗后体重指数(BMI)与甘油三酯 (TG)呈正相关 (r=0 391;P =0 0 14 ) ;体脂指标中IAF与低密度脂蛋白 (LDL)呈正相关 (r =0 4 38;P =0 0 1)。结论　APS治疗急性期体脂分布具腹型肥胖特征 ,男性更明显 ,并伴有血脂增高     

The time-dependent change of insulin secretion in schizophrenic patients treated with olanzapine

The second generation antipsychotic drugs (SGAs) are effective in treating patients with schizophrenia and have been considered as the first line therapy. Recently, increasing attention has been drawn to the potential diabetogenic effect of these novel antipsychotics. The goal of this study was to evaluate the time-dependent effects of olanzapine treatment on pancreatic beta cell function in SGA-naïve schizophrenic patients. Forty-two schizophrenic subjects received olanzapine therapy for 8 weeks and thirty-three of them completed the trial. Of whom 33 completers (21 male, mean ± SD age: 37.6 ± 8.0 years) were inpatients and unexposed to SGA. The metabolic parameters were quantitatively assessed at weeks 0, 2, 4, and 8 by the intravenous glucose tolerance test. After 56-day olanzapine treatment, subjects had significant increases in body weight and as well as in the levels of triglyceride, total cholesterol, and low-density lipoprotein. Insulin secretion significantly decreased at week 2, returned to baseline at week 4, and significantly increased at week 8. Of the total samples, 18.2% and 33.3% of them met the criteria for significant weight gain and metabolic syndrome after 8-week olanzapine treatment, respectively. This study indicates that olanzapine-treated schizophrenic patients displayed biphasic changes in insulin secretion to a hyperglycemic challenge. The results of this study support that olanzapine might directly influence pancreatic beta cell function.     

Plasma nitric oxide and leptin values in patients with olanzapine-induced weight gain

We previously investigated leptin levels in antipsychotic-induced weight gain and found that atypical antipsychotic, especially clozapine and olanzapine-induced weight gain is related to increased levels of leptin. It has been suggested that nitric oxide (NO) is a potential regulator of leptin-induced lipolysis. To explore the pathophysiology of weight gain during atypical antipsychotic treatment, we planned to investigate olanzapine's influence on leptin and NO levels and weight gain. The study comprised 21 patients with schizophrenia who were enrolled in olanzapine monotherapy, and 21 healthy controls. The fasting plasma NO and leptin levels were measured in both patients and controls at baseline. The patients were also evaluated at sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, serum leptin and NO levels. At baseline, the mean leptin level in the olanzapine group was not different compared to that in controls after BMI or age adjustment. A significant increase in leptin levels by means of olanzapine use was seen (P<0.01). Higher plasma NO levels were observed in patients with schizophrenia compared with the control group at baseline (P<0.01). At the evaluation of week 6, a significant decrease in the mean plasma NO level was found in the olanzapine group (P<0.05). The changes in total PANSS scores were correlated with change in leptin levels (r=0.58, P<0.05), and with the change in weight (r=0.54, P<0.05). In addition, there was a severe significant negative correlation between the changes in leptin levels and NO levels (r=0.73, P<0.01). The results confirmed that leptin and NO might be associated with olanzapine-induced weight gain.     

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

BACKGROUND: Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment. METHODS: A Medline search was performed for papers published from January 1999 to January 2007 using key words antipsychotic, atypical antipsychotic, and individual atypical antipsychotic drug names cross-referenced with leptin, ghrelin, and adiponectin. RESULTS: The bulk of the published work focused on changes in body weight and serum leptin, with far less data on ghrelin, and adiponectin, and nonweight metabolic changes. Leptin changes were directly related to a medication's weight gain liability, with no added antipsychotic effects on leptin signaling. Conflicting results emerged for the other markers, but all three long-term studies on ghrelin showed increased levels in patients on atypical antipsychotics with weight gain liabilities. CONCLUSIONS: Leptin increases during antipsychotic treatment are a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology. Preliminary long-term data show increased ghrelin levels, but this finding must be replicated. The association with antipsychotic effects on glucose and lipid metabolism and these hormones remains virtually unstudied. Future research should indicate whether ghrelin and other peptide hormones may be useful predictors of weight gain or metabolic changes in patients on antipsychotics.     

Neural changes associated with appetite information processing in schizophrenic patients after 16 weeks of olanzapine treatment

There is evidence that some atypical antipsychotics, including olanzapine, can produce unwanted metabolic side effects, weight gain and diabetes. However, neuronal correlates of change related to food information processing have not been investigated with these medications. We studied the effect of a pharmacological manipulation with an antipsychotic known to cause weight gain on metabolites, cognitive tasks and neural correlates related to food regulation. We used functional magnetic resonance imaging in conjunction with a task requiring visual processing of appetitive stimuli in schizophrenic patients and healthy controls before and after 16 weeks of antipsychotic medication with olanzapine. In patients, the psychological and neuronal changes associated following the treatment correlated with appetite control measures and metabolite levels in fasting blood samples. After 16 weeks of olanzapine treatment, the patients gained weight, increased their waist circumference, had fewer positive schizophrenia symptoms, a reduced ghrelin plasma concentration and an increased concentration of triglycerides, insulin and leptin. In premotor area, somatosensory cortices as well as bilaterally in the fusiform gyri, the olanzapine treatment increased the neural activity related to appetitive information in schizophrenic patients to similar levels relative to healthy individuals. However, a higher increase in sensitivity to appetitive stimuli after the treatment was observed in insular cortices, amygdala and cerebellum in schizophrenic patients as compared with healthy controls. Furthermore, these changes in neuronal activity correlated with changes in some metabolites and cognitive measurements related to appetite regulation.     

Rapid leptin elevation after initiation of olanzapine?

Weight gain is a common adverse effect associated with olanzapine treatment. Another side effect of olanzapine treatment is a significant increase in circulating leptin levels. This preliminary study monitored the changes in leptin levels for 2 weeks after olanzapine treatment had been initiated. The relationship between the changes in circulating leptin levels and alterations in body weight in 9 patients with schizophrenia who received olanzapine was examined. The results showed that olanzapine may cause a surge in circulating leptin levels before weight gain is manifested. Moreover, higher pretreatment circulating leptin levels predicted lower weight gains after olanzapine treatments (r = -0.93; p < 0.05) after controlling for the effect of sex.