Weight gain during treatment of bipolar I patients with olanzapine

BACKGROUND: Body weight increase during long-term treatment with olanzapine in schizophrenia patients is well documented, but weight gain and its association with other medical measures are less well evaluated in bipolar disorder patients. METHOD: We analyzed data from a 3-week, randomized, placebo-controlled trial of olanzapine for acute mania in DSM-IV bipolar I patients, followed by open continuation treatment with olanzapine up to a year. We examined factors associated with increased body mass index (BMI), including ratings of clinical change and selected physiologic measures. RESULTS: Among 113 subjects treated with olanzapine for a mean +/- SD of 28.6 +/- 19.9 weeks, BMI increased from a baseline mean of 28.8 +/- 6.2 kg/m(2), by 7.9 +/- 10.8% (p < .001), into the obese range (31.0 +/- 6.1 kg/m(2)). Initial BMI change (first 3 weeks of drug exposure) predicted final BMI increases (Spearman rank correlation r(s) = 0.32, p < .001). History of longer illness (p = .006) and lifetime substance abuse (p = .02) were associated with below-median BMI increases. BMI increased much more among 40 subjects achieving symptomatic recovery than in the 73 who did not (by 11.9 +/- 13.2% vs. 5.3 +/- 7.7%; p = .004), with correspondingly longer olanzapine exposure (44.7 +/- 11.8 vs. 19.7 +/- 17.7 weeks; p < .001) at similar doses. On average, serum cholesterol increased 4.8 times more (17.5% vs. 3.6%) and endpoint cholesterol levels were newly 240 mg/dL or greater 3.6 (95% CI = 1.5 to 8.0) times more frequently in subjects with above-median BMI gain, who also experienced significantly larger increases in systolic and diastolic blood pressure, pulse rates, and nonfasting serum glucose than low-BMI-gain subjects. CONCLUSIONS: Weight gain associated with long-term olanzapine treatment for mania was common, substantial, time-dependent, predicted by initial increases, and temporally associated with significant changes in cardiovascular and metabolic measures in bipolar I patients with prolonged illness and already-high basal BMI. An association of weight gain with favorable clinical response probably reflects longer olanzapine treatment.     

Weight gain and antipsychotic medication: differences between antipsychotic-free and treatment periods.

BACKGROUND: We performed a retrospective analysis of data involving 121 inpatients to examine the rate of weight gain during antipsychotic-free periods and during treatment with various antipsychotic drugs. METHOD: Data were analyzed to determine differences in weekly weight change during antipsychotic-free (N = 65), typical antipsychotic (N = 51), or atypical antipsychotic (N = 130) treatment periods. Atypical antipsychotic treatment periods were further subdivided into olanzapine (N = 45), clozapine (N = 47), or risperidone (N = 36) treatment periods. A paired comparison was conducted on 65 patients who had an antipsychotic-free treatment period preceding or following a neuroleptic drug treatment period. In addition, patients were classified as either non-obese (with a body mass index [BMI] < or = 29.9 kg/ml) or obese (BMI > or = 30.0 kg/m2) to test whether the rate of weight gain during treatment periods was related to initial BMI. RESULTS: Across all treatment periods, weekly weight gain was as follows: 0.89 lb/wk (0.40 kg/wk) on atypical antipsychotic medication, 0.61 lb/wk (0.27 kg/wk) on typical antipsychotic medication, and 0.21 lb/wk (0.09 kg/wk) on no antipsychotic medications. The atypical antipsychotic versus antipsychotic-free comparison was significant (F = 3.51; df = 2,231; p = .031), while the typical antipsychotic versus antipsychotic-free comparison was not. Among the individual atypical antipsychotic medications, significantly more weight gain occurred during olanzapine treatment (1.70 lb/wk) (0.76 kg/wk) than with either clozapine (0.50 lb/wk) (0.22 kg/wk) or risperidone (0.34 lb/wk) (0.15 kg/wk) treatments (F = 7.77; df = 2,117; p = .001). In the paired analysis with patients serving as their own controls, the difference between weekly weight gain during atypical antipsychotic treatment and antipsychotic-free treatment was significant (t = -3.91; df = 44; p = .001), while the difference between weight gain during typical antipsychotic treatment and antipsychotic-free treatment was not significant. With the individual drugs. treatment with both olanzapine and clozapine caused significantly higher weekly weight gain than antipsychotic-free treatment (p = .001 and p = .036, respectively). while treatment with risperidone did not. Non-obese patients (BMI < 29.9 kg/m2) and obese patients (BMI > 30.0 kg/m2) did not differ significantly in their weight gain during typical or atypical antipsychotic treatment. CONCLUSION: Treatment with atypical antipsychotics was associated with more weight gain than treatment with typical antipsychotics. Among the atypical drugs, olanzapine was associated with more weight gain than either clozapine or risperidone. The patient's admission BMI was not associated with the amount of weight gained during subsequent antipsychotic treatment.     

Weight gain over 4 months in schizophrenia patients: a comparison of olanzapine and risperidone

Weight gain frequently accompanies treatment with antipsychotics. In order to determine whether newer antipsychotic agents differ from each other with respect to weight gain, we compared two cohorts of patients with DSM-IV schizophrenia who had newly started treatment with either risperidone or olanzapine. After obtaining informed consent, data regarding body weight and height were culled from existing medical records of 100 patients (50 patients in each treatment group). Baseline body weight, close to the time of starting the new medication, and body mass index [BMI = weight (kg)/height (m) squared] were compared to the body weight and BMI following 4 months of treatment. There was no significant change in mean body weight or BMI in the group treated with risperidone (baseline weight = 83.1 kg +/- 20.5, follow-up = 82.8 kg +/- 19.9; matched pair t = 0.66, P = n.s.; baseline BMI = 29.6 +/- 9.4, follow-up = 29.5 +/- 9.1; matched pair t = 0.79, P = n.s.). However, in the group treated with olanzapine, there was a significant increase in both mean body weight and BMI (baseline weight = 84.9 kg +/- 25.0, follow-up = 87.1 kg +/- 25.1; matched pair t = 4.62, P < 0.001; baseline BMI = 29.5 +/- 7.4, follow-up = 30.3 +/- 7.5; matched pair t = 4.43, P < 0.001). In this naturalistic study, treatment with olanzapine was associated with a mean weight gain of about 2 kg from baseline, in patients with schizophrenia, while treatment with risperidone was associated with no mean weight change.     

Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: A randomized controlled trial

BACKGROUND: The purpose of this study was to compare an early behavioral intervention (EBI) with nonstructured standard physical care (routine care intervention [RCI]) in preventing antipsychotic-induced weight gain in drug-naive first-episode psychosis patients. METHOD: Sixty-one patients with a DSM-IV-diagnosed psychotic disorder were first randomly assigned to 3 different antipsychotic treatments (risperidone [N = 23], olanzapine [N = 18], and haloperidol [N = 21]) and subsequently randomly assigned to the intervention condition (EBI, N = 35) or RCI (N = 27). EBI was specifically designed to teach strategies to enhance control over factors associated with antipsychotic-induced weight gain and consisted of 8 flexible intervention modules that incorporated behavioral interventions, nutrition, and exercise. In the RCI group, patients were informed about potential weight gain and advised to increase their exercise and limit food intake. Body weight and body mass index were measured at baseline and then weekly for 3 months. In addition to change in weight and body mass index, a third outcome measure was the proportion of patients who had gained more than 7% of their body weight at 3 months. Participating patients were referred between August 2002 and September 2004. RESULTS: All 61 participants completed the study. Patients in the EBI group gained significantly less weight (mean = 4.1 kg, SD = 4.0) than those allocated to the RCI group (mean = 6.9 kg, SD = 4.5) (p < .01) during the 3-month follow-up period. Similar findings were obtained when both groups were compared on treatment-induced change in body mass index, which was significantly less in the EBI group than in the RCI group (1.40 vs. 2.39 kg/m2) (p < .01). Accordingly, significantly fewer patients in the EBI group (N = 11; 39.3%) than in the RCI group (N = 26; 78.8%) (p < .002) increased their baseline weight by more than 7%, the cutoff for clinically meaningful weight gain. CONCLUSIONS: EBI was effective in attenuating antipsychotic-induced weight gain in a drug-naive first-episode psychosis cohort. Patients displayed good adherence to this type of preventive intervention.     

Weight management program for treatment-emergent weight gain in olanzapine-treated patients with schizophrenia or schizoaffective disorder: A 12-week randomized controlled clinical trial

BACKGROUND: The main objective was to assess the efficacy of a weight management program designed for outpatients taking olanzapine for schizophrenia or schizoaffective disorder and to compare these patients with a randomized control group. The effects of the weight management program were also assessed with regard to safety and quality of life. METHOD: Forty-eight patients were enrolled in a 12-week, randomized, multicenter weight management study. Thirty-three patients were randomly allocated to an intervention group in which they received olanzapine within a weight management program. Fifteen patients were allocated to a control group in which they were given olanzapine treatment as usual outpatients. Weight, body mass index (BMI), and measurements of safety and quality of life were evaluated. The study was conducted from January 7, 2003, to September 16, 2003. RESULTS: Thirty-six patients (75%) completed this study. We found significant differences in weight (-3.94 +/- 3.63 kg vs. -1.48 +/- 1.88 kg, p = .006) and BMI (-1.50 +/- 1.34 vs. -0.59 +/- 0.73, p = .007) change from baseline to endpoint between the intervention and control groups, respectively. Significant differences in weight reduction were initially observed at week 8 (p = .040). No significant differences were found with regard to the safety outcomes. When the ratio of low-density lipoproteins to high-density lipoproteins was calculated, change from baseline was greater in the intervention group than the control group (-0.19 vs. -0.04), but the difference was not statistically significant (p = .556). After the completion of the weight management program, there was a trend toward statistical difference in the physical health score changes between the weight management and control groups (1.12 in the intervention group vs. -0.93 in the control group, p = .067). CONCLUSION: The weight management program was effective in terms of weight reduction in patients with schizophrenia or schizoaffective disorder taking olanzapine and was also found to be safe in terms of psychiatric symptoms, vital signs, and laboratory data. In addition, such a weight management program might improve quality of life in patients with schizophrenia or schizoaffective disorder with respect to their physical well-being.     

Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study

OBJECTIVE: To evaluate weight gain associated with olanzapine, risperidone, and haloperidol treatment and its clinical risk factors in adolescent patients. METHOD: The study was conducted at three adolescent psychiatric departments in two mental health centers in the Tel Aviv area. All patients were Jewish Israelis. Weight and body mass index (BMI) of hospitalized adolescents treated with olanzapine (n = 21), risperidone (n = 21), or haloperidol (n = 8) were prospectively monitored on a weekly basis for the first 12 weeks of treatment. Various clinical risk factors were tested for association with weight gain. RESULTS: The olanzapine and risperidone groups experienced significant weight gain between baseline and endpoint (p < .01), whereas the average weight of the haloperidol group did not change. Average weight gain was significantly higher for the olanzapine group (7.2 +/- 6.3 kg, 11.1% +/- 7.8%) than for the risperidone (3.9 +/- 4.8 kg, 6.6% +/- 8.6%) and haloperidol (1.1 +/- 3.3 kg, 1.5% +/- 6.0%) groups. Extreme weight gain (>7%) was recorded in 19 patients (90.5%), 9 patients (42.9%), and 1 (12.5%) patient, respectively Gender (males), low concern about gaining weight (females), low baseline BMI, and paternal BMI were positively correlated with weight gain, whereas previous neuroleptic history, neuroleptic dosage, response to treatment, and illness duration were not. CONCLUSIONS: Olanzapine and risperidone are associated with extreme weight gain in adolescents, much higher than that reported in adults. This side effect should be taken into consideration before prescribing these medications, especially in patients at high risk.     

Treatment with olanzapine, risperidone or typical antipsychotic drugs in Asian patients with schizophrenia

OBJECTIVE: To examine clinical outcomes in Asian patients with schizophrenia receiving monotherapy with olanzapine, risperidone or typical antipsychotics in naturalistic settings. METHOD: In this report, data from the first 12 months of the prospective, observational, 3-year Intercontinental Schizophrenia Outpatient Health Outcomes study are presented for patients from participating Asian countries (Korea, Taiwan and Malaysia) who were started on, or switched to, monotherapy with olanzapine (n = 484), risperidone (n = 287) or a typical antipsychotic drug (n = 127) at baseline. RESULTS: At 12 months, overall reduction in the score of Clinical Global Impressions-Severity of Illness rating scale was greatest with olanzapine (p < 0.001 vs typical agents), followed by risperidone (p = 0.007 vs typical agents) treatment. Olanzapine treatment was found to have significantly better effects than typical agents on negative and depressive symptom scores, and significantly greater improvements than risperidone on negative and cognitive symptoms. The occurrence of extrapyramidal symptoms was least likely with olanzapine (p < 0.001 vs typical agents, and p = 0.012 vs risperidone), while the estimated odds of tardive dyskinesia were greatest in the typical treatment group (p = 0.046 vs olanzapine, and p = 0.082 vs risperidone). Mean weight increase was greater for olanzapine-treated patients compared with the other agents (p = 0.030 vs typical agents and p < 0.001 vs risperidone). The risk of menstrual disturbance was relatively high with risperidone when compared with olanzapine treatment (p < 0.001). CONCLUSIONS: The results of this observational study indicate that, in Asian patients with schizophrenia, olanzapine may offer benefits when compared with typical agents or risperidone. However, the significantly greater odds of weight gain should be considered in the clinical management of olanzapine-treated patients.     

Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial

BACKGROUND: Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables. METHODS: Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment. RESULTS: The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels. CONCLUSIONS: Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.     

Weight gain induced by haloperidol, risperidone and olanzapine after 1 year: findings of a randomized clinical trial in a drug-naïve population

BACKGROUND: There is little information about weight gain induced by antipsychotics at long-term. OBJECTIVE: To quantify the weight gain induced by first (haloperidol) and second generation antipsychotics (olanzapine and risperidone) in a cohort of drug-na?ve subjects after 1 year of treatment. METHODS: This is a prospective, randomized clinical trial, including a representative sample of first episode psychotic incident cases from a population area of 555.000 people. The main outcome measures were changes in body weight and body mass index at 3 months and at 12 months. Both a per protocol analysis and an intention to treat analysis were conducted. RESULTS: A total of 164 drug-na?ve patients were included. At 12 months 144 patients were evaluated. Of them, 66% completed the protocol and 34% needed treatment switch. We found statistically significant differences in weight gain at 3 months: 3.8 kg (+/-4.1) for haloperidol, 5.9 kg (+/-5.1) for risperidone and 8.4 kg (+/-5.0) for olanzapine (F=7.045; p=0.002). After 1 year the difference in weight gain had disappeared: 9.7 kg (+/-5.7) for haloperidol, 8.9 kg (+/-8.8) for risperidone and 10.9 kg (+/-7.2) for olanzapine (F=0.817; p=0.445). CONCLUSIONS: Drug-na?ve patients experience an extraordinary weight gain after 1 year of treatment with haloperidol, olanzapine or risperidone. The main difference among these treatments is the pattern of weight gain but not the final amount of weight gain.     

Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia

BACKGROUND: Weight change and the weight-related health factors of nonfasting serum glucose, serum cholesterol, and diastolic blood pressure levels were analyzed in patients with DSM-III-R schizophrenia and related disorders who received treatment with olanzapine for up to 3 years, and comparisons were made to patients treated with haloperidol. Baseline body mass index (BBMI; kg/m2) and dose (mg/day) were investigated as predictors of long-term weight change experienced during olanzapine treatment. METHOD: This analysis retrospectively examined 573 patients receiving olanzapine and 103 patients receiving haloperidol for 39 weeks or more from a study of 1,996 patients randomly assigned 2:1 to either olanzapine, 5 to 20 mg/day, or haloperidol, 5 to 20 mg/day. After 6 weeks of acute therapy, patients continued for 1 year or more with either double-blind or open-label olanzapine therapy or double-blind haloperidol therapy. RESULTS: Mean weight gain for olanzapine-treated patients observed for a median of 2.54 years trended toward a plateau after the first 39 weeks of treatment with a last-observation-carried-forward mean weight change of 6.26 kg (13.8 lb) and a median of 5.90 kg (13.0 lb). This was significantly higher than that for haloperidol-treated patients, whose mean weight gain was 0.69 kg (1.5 lb) after 1.15 years (p < .001). Patients with higher BBMI (> 27.6) gained significantly less weight during treatment with olanzapine than their lighter counterparts (BBMI < 27.6) (p < .001). The effect of olanzapine dose on weight was not significant (p > or = . 183). Median serum glucose at endpoint was not significantly associated (p = .096) with weight change for olanzapine. Median serum cholesterol and diastolic blood pressure for olanzapine-treated patients at endpoint showed a relationship with weight change that was statistically (p < or = .001) but not clinically significant. The difference in incidence of elevated serum glucose, cholesterol, or diastolic blood pressure between olanzapine and haloperidol therapy groups was not different (p > .05). CONCLUSION: Mean weight gain during olanzapine treatment trended toward a plateau after the initial 39 weeks of treatment with no further significant gain out to 3 years. Higher BBMI was predictive of a lower long-term weight gain, while dose was not a significant predictor of greater longer term weight change. The relationship between weight change and glucose was not statistically significant. The association between weight change and changes in cholesterol as well as changes in diastolic blood pressure was statistically significant but not considered clinically relevant based on the ranges observed.     

The efficacy of mifepristone in the reduction and prevention of olanzapine-induced weight gain in rats

Atypical antipsychotics, such as olanzapine, have been associated with clinically significant weight gain. Changes to the hypothalamic pituitary adrenal axis may partially mediate this weight increase. Two experiments were conducted to test the effects of mifepristone on both mitigating and preventing olanzapine-induced weight gain. In the first experiment, adult female Sprague-Dawley rats gained significantly more weight on average when administered olanzapine for 35 days compared to vehicle controls. Subsequently, the olanzapine-treated rats were randomized to three dose levels of mifepristone (20, 60, and 200 mg/kg) in conjunction with olanzapine. Weight measurements were taken for 21 additional days. Rats receiving olanzapine plus mifepristone rapidly lost a significant portion of the weight gained during the olanzapine only phase (p = 0.0001). Rats in the 200 mg/kg dose group had significantly less abdominal fat compared to controls (p < 0.001) at study end. In the second experiment, daily mifepristone (20, 60, 200 mg/kg) initiated concomitantly with olanzapine was compared with olanzapine alone to determine if mifepristone prevented olanzapine-induced weight gain. After 21 days of treatment, mifepristone treated rats gained significantly less weight and had significantly less abdominal fat than rats administered olanzapine alone (p = 0.0002). Results suggest that mifepristone, a potent glucocorticoid antagonist, may both reduce and prevent olanzapine-induced weight gain in rats.     

G-protein ��3 Subunit Gene 825C/T Polymorphism Is Not Associated with Olanzapine-Induced Weight Gain in Korean Schizophrenic Patients

Objective

Weight gain is a possible adverse effect of the use of antipsychotics, and is an important factor for long-term health and treatment compliance. Olanzapine is an atypical antipsychotic known to cause considerable weight gain. A relationship between weight gain and the G protein β3 subunit gene (GNB3) 825C/T polymorphism has been reported. We therefore examined this possible association in a Korean schizophrenic patient group receiving olanzapine treatment.

Methods

Weight and height measurements were obtained prior to starting olanzapine and measured again after long-term treatment. Genotyping for the 825C/T polymorphism was performed using a PCR-based method.

Results

We found that long-term treatment with olanzapine resulted in mean gains in weight and body mass index (BMI) of 5.2 kg and 1.93 kg/m², respectively. There was a no significant difference in the mean body weight change from baseline to the endpoint after olanzapine treatment between the genotype groups (p=0.796). There were also no significant differences in genotype or allele frequencies between the severe weight-gain (more than 10%) and minimal weight-gain (less than 10%) groups (χ²=0.037, p=0.98; χ²=0.020, p=0.89).

Conclusion

The finding from this study thus does not support a relationship between the GNB3 825C/T polymorphism and weight gain in Korean schizophrenic patients receiving olanzapine treatment.     

Open label study of the effect of amantadine on weight gain induced by olanzapine

The purpose of the present paper was to investigate the effects of the dopamine agonist amantadine in those patients with weight gain induced by olanzapine. An open trial was conducted in those patients who gained >3 kg in weight induced by olanzapine use. All subjects were evaluated by weight, body mass index (BMI), the Brief Psychiatric Rating Scale (BPRS), and the Extrapyramidal Symptom Rating Scale (ESRS) before and after the use of amantadine in addition to olanzapine. Twenty-five of 30 enrolled patients completed the present study. Mean bodyweight and BMI was increased by 6.44 +/- 4.42 kg and 5.04 +/- 3.47 kg/m2 significantly with olanzapine alone (P < 0.001). When amantadine and olanzapine were used together, the average weight and BMI decreased by 1.07 +/- 3.19 kg and 0.84 +/- 2.5 kg/m2, but did not have statistical significance. The average values of BPRS showed a significant decrease (P < 0.001). No significant changes were present in ESRS. Amantadine did not have an effect on weight gain induced by olanzapine. Randomized placebo-controlled prospective studies are needed.     

二甲双胍对奥氮平所致精神分裂症患者体质量增加的影响

目的 验证二甲双胍预防奥氮平引起精神分裂症患者的体质量增加和糖代谢紊乱的效果.方法 将37例未服过抗精神病药的精神分裂症患者,随机分为奥氮平(15 mg/d)联合二甲双胍组(750 ms/d;A组,18例)和奥氮平(15 mg/d)联合安慰剂组(B组,19例),治疗12周.于治疗前和治疗第4周末、8周末及12周末测定空腹血糖、胰岛素(INS)、身高、体质量、腰围、臀围,计算体质量指数(BMI)、腰臀比(WHR)、胰岛素抵抗指数(IRI)及治疗12周末体质量增加大于7%的比率.用阳性症状量表(SAPS)、阴性症状量表(SANS)于治疗前和治疗12周末评定疗效.结果 治疗12周末,A、B两组的体质量、BMI、WHR及B组患者的空腹INS和IRI较治疗前均升高(P＜0.05).治疗第8,12周末,B组的体质量、BMI、空腹INS和IRI的变化值高于A组(P＜0.05).B组体质量增加大于7%的比率(63%,12例)高于A组(17%,3例;P＜0.01).A、B两组的SAPS及SANS评分均显著低于治疗前(均P＜0.05),但组间差异均无统计学意义(P＞0.05).结论 二甲双胍能有效减轻奥氮平引起的体质量增加和糖代谢紊乱.     

Weight gain associated with clozapine,olanzapine and risperidone in children and adolescents

Summary. The study was aimed at the evaluation of weight gain associated with atypical antipsychotics and its clinical risk factors in children and adolescents. Weight and body mass index (BMI) of initially hospitalised patients treated with clozapine (n = 15), olanzapine (n = 15), and risperidone (n = 15) were prospectively monitored on a weekly basis for the first 6 weeks. Different clinical risk factors were tested for their association with weight gain in the three groups. All three groups experienced significant weight gain between baseline and endpoint (p < 0.0001). For all weight measures, planned comparisons were all significant between olanzapine vs. clozapine and risperidone, respectively. Average weight gain was significantly higher for the olanzapine group (mean = 4.6 kg, SD = 1.9) than for the risperidone (mean = 2.8 kg, SD = 1.3) and clozapine (mean = 2.5 kg, SD = 2.9) groups. Olanzapine and risperidone, but not clozapine, caused a disproportionately higher weight gain in children and adolescents in comparison to adults.     

探讨复方丹参滴丸治疗奥氮平所致代谢综合征的疗效及安全性

目的初步探讨复方丹参滴丸治疗奥氮平所致代谢综合征的疗效及安全性。方法本研究采用随机、单盲、前瞻性对照研究,选取符合国际疾病分类第10版(ICD-10)中精神分裂症确诊标准的住院女患者45例。在奥氮平治疗的基础上,按照随机数字表法分为干预组(联合复方丹参滴丸治疗,n=22)和对照组(n=23),并在0、4、8和12周末进行体质量、体重指数(body max index,BMI)、血糖和胰岛素抵抗进行盲法测定和评估。结果最终37例(82.2%)完成了本研究,干预组18例,对照组19例。治疗8周末,干预组胰岛素抵抗变化值均低于对照组(0.29±0.62vs 1.03±0.64),差异均有统计学意义(P0.05)。治疗12周末,干预组体质量、BMI和胰岛素抵抗变化值低于对照组(1.87±2.81vs 5.14±3.67、0.53±0.56vs 1.92±1.03和0.22±0.66vs 1.49±0.67),差异均有统计学意义(P0.05)。2组不良反应差异无统计学意义(P0.05)。结论复方丹参滴丸一定程度上能有效减轻奥氮平所致的代谢综合征,疗效佳、安全性好,但向临床推广应用需进一步探讨。     

Behavioral treatment of obesity in patients taking antipsychotic medications

OBJECTIVE: Antipsychotic medications are associated with weight gain and metabolic dysregulation, yet little is known about the management of obesity among individuals with severe and persistent mental illness. Thus we sought to evaluate the potential utility of a behavioral weight control program for this population. METHOD: Outpatients receiving psychiatric care at a university medical center who had a body mass index (BMI; weight in kg/[height in m](2)) >or= 30 and were currently taking antipsychotic medication participated in a 12-week group behavioral weight control program. A medical chart review was conducted for each participant's body weight over the 10 months prior to beginning the program. A multiple baseline design was used to determine the impact of the intervention on BMI through 12-month posttreatment follow-up. We also assessed self-reported eating behavior, physical activity, and health-related quality of life. Data were collected from October 2000 to July 2003. RESULTS: Among 35 patients who began the program, 29 (83%) completed treatment, with mean (+/- SD) weight loss of 5.04 (+/- 7.52) pounds (p = .001) and improvements in eating, activity, and quality of life. At 3-month posttreatment follow-up (N = 27; 77%), total mean weight loss was 7.14 (+/- 11.47) pounds (p = .003). Results of a longitudinal model based on general estimating equations indicated that, relative to the pretreatment period, BMI decreased significantly during treatment and remained stable through 12-month posttreatment follow-up. CONCLUSION: Behavioral weight control is a promising approach to the treatment of obesity among outpatients taking antipsychotic medications, but longer and more robust interventions are needed.     

氟哌啶醇与奥氮平治疗精神分裂症疗效和安全性的随机对照研究

目的比较氟哌啶醇与奥氮平治疗精神分裂症的疗效及安全性。方法将符合精神分裂症诊断标准的住院患者按照1:2比例随机分为氟哌啶醇(n=120)和奥氮平治疗组(n=252),进行为期6周的治疗观察;于基线及治疗2、4、6周末评定阳性和阴性症状量表(positive and negative syndrom scale,PANSS),锥体外系副反应量表(rating scale for extrapyramdal side effects,RSESE)、静坐不能评定量表(barnes akathisia rating scale,BARS)和异常不自主运动量表(abnormal involuntary movement scale,AIMS);计算体质量指数(body mass index,BMI);基线及治疗4、6周末测定空腹血糖、血脂和肝功能等指标。结果氟哌啶醇组与奥氮平组基线PANSS总分差异无统计学意义;第6周末氟哌啶醇组PANSS总分低于奥氮平组(53.31±1.64 vs.58.05±1.02),减分率高于后者(60.63±2.86%vs.52.45±1.80%),均P<0.05;两组有效率(66.7%vs.62.7%)差异无统计学意义。第6周末氟哌啶醇组BMI较基线的变化值(0.08±0.20 kg/m2vs.0.91±0.12 kg/m2)、谷丙转氨酶异常病例数比例(16.98%vs.28.07%)均低于奥氮平组(P<0.05);第4周末氟哌啶醇组甘油三酯较基线的变化值低于奥氮平组(0.24±0.12 mmol/L vs.0.57±0.07 mmol/L),P<0.05。氟哌啶醇组锥体外系不良反应发生率(73.3%)明显高于奥氮平组(10.71%),P<0.05。结论在精神分裂症急性期,氟哌啶醇治疗有效率与奥氮平相当,对体重、血脂、转氨酶的影响较小,但锥体外系不良反应发生率较高。     

Double-blind, placebo-controlled investigation of amantadine for weight loss in subjects who gained weight with olanzapine

OBJECTIVE: This study sought to determine if amantadine affects weight gain in psychiatric patients taking olanzapine. METHOD: Twenty-one adults who had gained at least 5 lb with olanzapine were randomly assigned to receive amantadine (N=12) or placebo (N=9) in addition to olanzapine. The length of time taking olanzapine ranged from 1 to 44 months. Body mass index, psychiatric status, and fasting blood levels were assessed at baseline and 12 weeks. RESULTS: Significantly fewer subjects taking amantadine gained weight, with a mean change in body mass index of -0.07 kg/m2 for the amantadine group and 1.24 kg/m2 for the placebo group. This effect remained significant when the authors controlled for baseline body mass index and length of olanzapine treatment. No changes in fasting glucose, insulin, leptin, prolactin, and lipid levels were seen. Positive and Negative Syndrome Scale scores remained stable. CONCLUSIONS: Amantadine induced weight stabilization in subjects taking olanzapine and was well tolerated.     

Metformin for prevention of weight gain and insulin resistance with olanzapine: a double-blind placebo-controlled trial.

OBJECTIVE: To assess whether metformin prevents body weight gain (BWG) and metabolic dysfunction in patients with schizophrenia who are treated with olanzapine. METHOD: Forty patients taking olanzapine (10 mg daily) were randomly allocated to a metformin (n = 20; 850 to 1700 mg daily) or placebo (n = 20) group in a 14-week double-blind study. Waist circumference (WC), BWG, body mass index (BMI) fasting glucose, insulin, and lipids were evaluated at baseline and at Weeks 7 and 14 of treatment. RESULTS: At Week 14, BWG (kg) was similar in the metformin group (5.5 kg) and the placebo group (6.3 kg), P = 0.4. There were no differences between the changes in BMI, WC, glucose, insulin, insulin resistance index (HOMA-IR), and plasma lipid levels observed in the treatment group and the placebo group; however, glucose levels decreased significantly after metformin administration (P = 0.02). The HOMA-IR decreased significantly in both groups, but 3 subjects from the placebo group developed fasting glucose levels greater than 5 mmol/L. After taking metformin, triglyceride levels increased, but the cholesterol profile improved significantly. CONCLUSIONS: Metformin did not prevent olanzapine-induced BWG. While some lipid parameters worsened during placebo, the HOMA-IR improved in both the placebo and the metformin groups. Carbohydrate metabolism impairment was not systematically observed during short-term olanzapine administration.