olanzapine and Overweight

Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain. Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Of these, four studies (n= 105) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index (BMI). Weighted mean difference (WMD) for body weight was 5.02 (95% CI 3.93, 6.10) kg lower with metformin as compared with placebo at 12 weeks. For waist circumference, the test for heterogeneity was significant (P= 0.00002, I(2) = 85.1%). Therefore, a random effects model was used to calculate WMD, which was 1.42 (95% CI 0.29, 3.13) cm lower with metformin as compared with placebo at 12 weeks. For BMI, WMD was 1.82 (95% CI 1.44, 2.19) kg m(-2) lower with metformin as compared with placebo at 12 weeks. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Humans; Hypoglycemic Agents; Metformin; Olanzapine; Overweight; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain

Schizophrenia is associated with a lowered bone mineral density. The antidiabetic and body weight lowering glucagon-like peptide-1 receptor agonist liraglutide has shown to mitigate overweight and impaired glucose tolerance associated with olanzapine and clozapine. As liraglutide has been proposed to affect bone metabolism, we evaluated the effect of liraglutide on bone turnover markers (BTM) in patients with prediabetes and schizophrenia treated with olanzapine or clozapine. Patients diagnosed with a schizophrenia spectrum disorder treated with the antipsychotic compounds clozapine and/or olanzapine, having prediabetes and a BMI above 27 kg/m

Topics: Adult; Antipsychotic Agents; Biomarkers; Body Weight; Bone and Bones; Bone Density; Bone Remodeling; Clozapine; Collagen Type I; Fasting; Humans; Hypoglycemic Agents; Liraglutide; Male; Middle Aged; Olanzapine; Overweight; Prediabetic State; Schizophrenia

Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16-week intervention were sustained beyond the intervention period.. One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide, and lipids comparing 1-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels.. From end of treatment to the 1-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI: -7.3 to -0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide.. The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Blood Glucose; Body Weight; C-Peptide; Clozapine; Denmark; Fasting; Female; Follow-Up Studies; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Lipid Metabolism; Liraglutide; Male; Middle Aged; Obesity; Olanzapine; Overweight; Placebos; Prediabetic State; Schizophrenia; Young Adult

Compared with the general population, patients with schizophrenia have a 2- to 3-fold higher mortality rate primarily caused by cardiovascular disease. Previous interventions designed to counteract antipsychotic-induced weight gain and cardiometabolic disturbances reported limited effects.. To determine the effects of the glucagon-like peptide-1 receptor agonist liraglutide added to clozapine or olanzapine treatment of schizophrenia spectrum disorders.. This randomized clinical double-blind trial enrolled participants at 2 clinical sites in Denmark. Of 214 eligible participants with a schizophrenia spectrum disorder, 103 were randomized to liraglutide or placebo. Participants received stable treatment with clozapine or olanzapine, were overweight or obese, and had prediabetes. Data were collected from May 1, 2013, through February 25, 2016.. Treatment for 16 weeks with once-daily subcutaneous injection of liraglutide or placebo. Trial drug therapy was titrated during the first 2 weeks of the study.. The primary end point was change in glucose tolerance estimated by a 75-g oral glucose tolerance test result. Secondary end points included change in body weight and cardiometabolic parameters.. Of the 103 patients undergoing randomization (60 men [58.3%] and 43 women [41.7%]), 97 were included in the efficacy analysis, with a mean (SD) age of 42.5 (10.5) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 33.8 (5.9). The liraglutide and placebo groups had comparable characteristics (mean [SD] age, 42.1 [10.7] vs 43.0 [10.5] years; 30 men in each group; mean [SD] body mass index, 33.7 [5.1] vs 33.9 [6.6]). A total of 96 randomized participants (93.2%) completed the trial. Glucose tolerance improved in the liraglutide group compared with the placebo group (P < .001). Altogether, 30 liraglutide-treated participants (63.8%) developed normal glucose tolerance compared with 8 placebo-treated participants (16.0%) (P < .001; number needed to treat, 2). Body weight decreased with liraglutide compared with placebo (-5.3 kg; 95% CI, -7.0 to -3.7 kg). Reductions in waist circumference (-4.1 cm; 95% CI, -6.0 to -2.3 cm), systolic blood pressure (-4.9 mm Hg; 95% CI, -9.5 to -0.3 mm Hg), visceral fat (-250.19 g; 95% CI, -459.9 to -40.5 g), and low-density lipoprotein levels (-15.4 mg/dL; 95% CI, -23.2 to -7.7 mg/dL) occurred with liraglutide compared with placebo. Adverse events with liraglutide affected mainly the gastrointestinal tract.. Liraglutide significantly improved glucose tolerance, body weight, and cardiometabolic disturbances in patients with schizophrenia spectrum disorders treated with clozapine or olanzapine.. clinicaltrials.gov Identifier: NCT01845259.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Female; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Liraglutide; Male; Middle Aged; Obesity; Olanzapine; Outcome Assessment, Health Care; Overweight; Prediabetic State; Schizophrenia

Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side effects as well as adjunctive treatments to inhibit these has been of major interest. The aim of this study was to investigate in healthy male volunteers (age: 36 ± 11 years; BW: 84 ± 12 kg; BMI=25.5 ± 2.5) whether adjunctive topiramate (TPM) administration opposes OLZ-induced weight gain over the course of 14 days treatment. In addition, we investigated behavioral, endocrine and metabolic characteristics as underlying and potentially predictive factors for weight regulation and/or metabolic derangements associated with OLZ and TPM treatment. While adjunctive TPM indeed reduced OLZ-induced weight gain (P<0.05, Mann-Whitney U), behavioral/metabolic/endocrine characteristics of OLZ treatment were not affected by TPM. Using multiple regression analysis, BW gain was the key factor explaining metabolic disturbances (e.g., plasma insulin- LDL interaction: P<0.01, R(2)=.320), and cumulative food intake during treatment was the best denominator of BW gain (P<0.01, R(2)=.534). Neither TPM treatment, nor its circulating levels, contributed to variation observed in ΔBW. In a second multiple regression analysis, we observed that a low baseline thyrotropin profile (TSHAUC) before the start of drug treatment was associated with an increase in ΔBW over the course of drug treatment (P<0.05, R(2)=.195). Adding TSHAUC as covariate revealed that adjunctive TPM treatment did attenuate OLZ induced BW gain (P<0.05, ANCOVA). Further exploration of the circulating thyroid hormones revealed that individuals with a low plasma TSH profile were also those that were most sensitive to adjunctive TPM treatment blocking OLZ-induced ΔBW gain. Others have shown that OLZ-induced BW gain is associated with improvement in brief psychiatric rating scores (BPRS); adjunctive TPM treatment may be a solution specifically for those subjects susceptible to OLZ-induced rapid weight gain who-on a therapeutic level-benefit most of OLZ treatment.

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Down-Regulation; Drug Antagonism; Fructose; Healthy Volunteers; Humans; Male; Middle Aged; Olanzapine; Overweight; Prognosis; Thyrotropin; Topiramate; Weight Gain; Young Adult

The primary aim of the present study was to assess the possible associations between dopaminergic, serotonergic, and glutamatergic system-related genes and adverse events after antipsychotic treatment in paranoid schizophrenia patients. The second aim of the study was to compare the intensity of these symptoms between atypical (ziprasidone and olanzapine) and typical (perazine) antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT, MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of side effects (changes in body weights and extrapyramidal symptoms (EPS)) was measured at baseline and after 12 weeks of antipsychotic treatment. After 3 months of therapy, the weight increase was the greatest in the group treated with olanzapine and the least in the group treated with ziprasidone. None of the examined gene polymorphisms was associated with the body weight changes. Perazine treatment was associated with the significantly highest intensity of EPS. None of the examined polymorphisms was associated with the changes in extrapyramidal adverse events after antipsychotic treatment. The selected polymorphisms are not primarily involved in changes in body weights and EPS related to antipsychotic treatment in paranoid schizophrenia patients.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Catechol O-Methyltransferase; Dopamine Plasma Membrane Transport Proteins; Female; Genotype; GluK3 Kainate Receptor; Humans; Male; Middle Aged; Monoamine Oxidase; Olanzapine; Overweight; Perazine; Piperazines; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Receptors, Kainic Acid; Schizophrenia, Paranoid; Serotonin Plasma Membrane Transport Proteins; Thiazoles; Weight Gain; Young Adult

Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Colon; Constipation; Cross-Sectional Studies; Diarrhea; Double-Blind Method; Finland; Humans; Incidence; Lactones; Laxatives; Obesity; Olanzapine; Orlistat; Overweight; Patient Dropouts; Prevalence; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Weight Loss

Olanzapine treatment has been associated with clinically meaningful weight increases, hypertriglyceridemia, insulin resistance, and diabetes mellitus. There are few options for olanzapine responders who fail other antipsychotic agents. Aripiprazole is a potent (high-affinity) partial agonist at D2 and 5-HT1A receptors and a potent antagonist at 5-HT2A receptor and is associated with less weight gain than olanzapine. We report the results of a 10-week placebo-controlled, double-blind crossover study that examined 15 mg/d aripiprazole's effects on weight, lipids, glucose metabolism, and psychopathology in overweight and obese schizophrenia and schizoaffective disorder subjects treated with a stable dose of olanzapine. During the 4 weeks of aripiprazole treatment, there were significant decreases in weight (P = 0.003) and body mass index (P = 0.004) compared with placebo. Total serum cholesterol (P = 0.208), high-density lipoprotein cholesterol (HDL-C; P = 0.99), HDL-2 (P = 0.08), HDL-3 (P = 0.495), and low-density lipoprotein cholesterol (P = 0.665) did not change significantly comparing aripiprazole treatment to placebo treatment. However, total serum triglycerides (P = 0.001), total very low-density lipoprotein cholesterol (VLDL-C; P = 0.01), and VLDL-1C and VLDL-2C (P = 0.012) decreased significantly during the aripiprazole treatment phase. The VLDL-3C tended lower during aripiprazole, but the decrease was not significant (P = 0.062). There was a decrease in C-reactive protein comparing aripiprazole treatment to placebo, although it did not reach significance (P = 0.087). The addition of aripiprazole to a stable dose of olanzapine was well tolerated and resulted in significant improvements on several outcome measures that predict risk for medical morbidity.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; C-Reactive Protein; Cholesterol; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Glucose; Humans; Male; Middle Aged; Obesity; Olanzapine; Overweight; Piperazines; Quinolones; Schizophrenia; Schizophrenic Psychology; Triglycerides

Major mental disorders are associated with an increased risk for obesity-related cardiovascular mortality, leading to interest in risk-reduction approaches that target weight and risk-related plasma lipids, including use of antipsychotic agents with low metabolic risk. This multicenter, randomized, double-blind study compared the metabolic effects of aripiprazole versus olanzapine in overweight persons with schizophrenia or schizoaffective disorder who were previously on olanzapine treatment.. In total, 173 subjects with DSM-IV-TR-defined schizophrenia or schizoaffective disorder were randomly assigned to receive aripiprazole (N = 88) or olanzapine (N = 85) for 16 weeks in a study conducted from March 30, 2004, to August 8, 2006. Primary and secondary endpoints were mean weight change from baseline and percentage change from baseline in fasting triglyceride levels, respectively.. At week 16, weight decreased significantly with aripiprazole versus olanzapine (-1.8 vs. +1.41 kg; p < .001). Significant differences in percentage change in triglyceride levels were observed with aripiprazole (decreases) versus olanzapine (increases) at all time-points. In addition, significantly more subjects receiving aripiprazole had clinically relevant (> or = 7%) weight loss versus olanzapine (11.1% vs. 2.6%; p = .038), and a lower percentage of subjects receiving aripiprazole had clinically relevant weight gain (2.5% vs. 9.1%; p = .082). Mean percentage changes in fasting total cholesterol and high-density lipoprotein cholesterol at week 16 were significantly different with aripiprazole versus olanzapine, with no significant effects on glycemic laboratory measures. Mean Clinical Global Impressions-Improvement (CGI-I) scores for both groups were in the range of "no change" to "minimal improvement." CGI-I endpoint scores were statistically significantly better with olanzapine (mean +/- SE = 3.09 +/- 0.16) versus aripiprazole (mean +/- SE = 3.74 +/- 0.15; p < .001), and more subjects discontinued aripiprazole (N = 32/88; 36%) than olanzapine (N = 22/85; 26%).. Significant improvements in weight and lipids observed during discontinuation of olanzapine and switch to aripiprazole treatment occurred with limited evidence of negative psychiatric effects, relative to uninterrupted continuation of olanzapine treatment. The results suggest that the potential value of therapeutic substitutions involving specific antipsychotic medications should be considered in overall efforts to reduce cardiovascular risk in this population.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Administration Schedule; Electrocardiography; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Obesity; Olanzapine; Overweight; Piperazines; Psychotic Disorders; Quinolones; Schizophrenia; Triglycerides

To investigate the long-term weight loss outcomes during usual clinical practice after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT).. In this open-label prospective study, 26 patients with schizophrenia who were clinically stable on olanzapine SOT treatment were switched to olanzapine ODT. All other aspects of treatment remained constant. Weight was recorded at 3, 6, and 12 months.. Patients incurred an average weight loss of 2.7 +/- 0.7 kg (p = 0.001) after switching patients from olanzapine SOT to olanzapine ODT at 12 months. Peak weight loss was observed at 6 months; however, significant weight loss was achieved as early as 3 months. The majority (81.9%) of patients lost weight, while 18.1% had no weight change or weight gain. Body mass index (BMI) significantly decreased by 1.0 +/- 0.3 kg/m(2) (p = 0.001). Interestingly, patients treated with higher doses of olanzapine (> or = 20 mg) incurred a greater weight loss of their body weight (5.6%), compared to those treated with lower doses (< 20 mg), who lost 1.9% of their body weight (p = 0.04).. This study demonstrated that, in usual clinical practice, switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained over 12 months.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Chemistry, Pharmaceutical; Chronic Disease; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Overweight; Prospective Studies; Psychotic Disorders; Schizophrenia; Weight Loss

Undesirable metabolic effects of modern antipsychotics, especially clozapine and olanzapine, merit development of new weight-control strategies, including pharmacologic ones. We investigated the feasibility of treatment with orlistat, a weight-control drug with no central effects, for overweight/obesity in clozapine- or olanzapine-treated male and female patients.. Add-on orlistat was prescribed for 16 weeks in a randomized, double-blind, placebo-controlled clinical trial to patients who were receiving stable clozapine or olanzapine medication and were aged 18 to 65 years, with no compliance with nonpharmacologic programs or hypocaloric diet required. The primary efficacy variable was body weight change. The study was conducted from 2004 through 2005.. Of 71 randomly assigned subjects, 63 were eligible for modified intent-to-treat analysis. While no statistically significant effect was observed in the whole population, male (but not female) patients benefited from treatment with orlistat (-2.36 kg vs. 0.62 kg on placebo, p = .011). There were 5 responders (16.1%) (those with >or= 5% weight loss) that received orlistat versus 2 responders (6.3%) that received placebo (number needed to treat = 11), but the difference was not statistically significant.. Without a hypocaloric diet, the effect of orlistat in overweight/obese clozapine-or olanzapine-treated patients is modest and may only be seen in men. More studies should define the optimal length of treatment and feasibility of combination of orlistat with behavioral programs in this population.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Obesity; Olanzapine; Orlistat; Overweight; Psychotic Disorders

Patients with schizophrenia have an increased prevalence of metabolic disturbances compared with the general population. However, the mechanisms underlying the metabolic side effects of antipsychotics are unknown. The aim of the present study was to compare the levels of high-density lipoprotein (HDL)-cholesterol in Japanese schizophrenia patients medicated with olanzapine, risperidone, or aripiprazole monotherapy.. This study was a post-hoc analysis of a nationwide survey, which included 433 Japanese outpatients with schizophrenia and 674 inpatients. A brief questionnaire was compiled that covered demographic data, systolic blood pressure, diastolic blood pressure, and HDL-cholesterol after reviewing the relevant literature and guidelines. To compare demographic and clinical characteristics, analysis of variance was performed for continuous variables and the chi-square test was performed for categorical variables. For comparisons of HDL-cholesterol levels among the three antipsychotic groups, analysis of covariance was carried out with age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference as confounding variables after stratification by body mass index (BMI) for each outpatient group and inpatient group.. This study reveals a difference in HDL-cholesterol levels in overweight Japanese inpatients with schizophrenia resulting from the use of different antipsychotics. In the post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group. Further studies incorporating more detailed evaluations, including diet and physical activity, are needed to clarify the differences in HDL-cholesterol according to antipsychotic use.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Body Mass Index; Cholesterol, HDL; Correlation of Data; Female; Humans; Japan; Male; Middle Aged; Olanzapine; Overweight; Prevalence; Risperidone; Schizophrenia; Surveys and Questionnaires; Waist Circumference

Topics: Antipsychotic Agents; Clozapine; Humans; Liraglutide; Obesity; Olanzapine; Overweight; Prediabetic State; Schizophrenia; Weight Gain

Antipsychotics frequently cause changes in glucose metabolism followed by development of weight gain and/or diabetes. Recent findings from our group indicated an influence of glucose-related genes on this serious side effect. With this study, we aimed to extend previous research and performed a comprehensive study on the peroxisome proliferator-activated receptor gamma (PPARG) and the adiponectin (ADIPOQ) genes. In 216 schizophrenic patients receiving antipsychotics for up to 14 weeks, we investigated single-nucleotide polymorphisms in or near PPARG (N=24) and ADIPOQ (N=18). Statistical analysis was done using ANCOVA in SPSS. Haplotype analysis was performed in UNPHASED 3.1.4 and Haploview 4.2. None of the PPARG or ADIPOQ variants showed significant association with antipsychotic-induced weight gain in our combined sample or in a refined subsample of patients of European ancestry treated with clozapine or olanzapine after correction for multiple testing. Similarly, no haplotype association could withstand multiple test correction. Although we could not find a significant influence of ADIPOQ and PPARG on antipsychotic-induced weight gain, our comprehensive examination of these two genes contributes to understanding the biology of this serious side effect. More research on glucose metabolism genes is warranted to elucidate their role in metabolic changes during antipsychotic treatment.

Topics: Adiponectin; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Haplotypes; Humans; Male; Middle Aged; Olanzapine; Overweight; Polymorphism, Single Nucleotide; PPAR gamma; Psychotic Disorders; Weight Gain; White People; Young Adult

The aim was to explore weight and body mass index (BMI) changes by baseline BMI in patients completing three years of monotherapy with various first- and second-generation antipsychotics in a large cohort in a post hoc analysis of three-year observational data. Data were analyzed by antipsychotic and three baseline BMI bands: underweight/normal weight (BMI <25 kg/m²), overweight (25-30 kg/m²) and obese (>30 kg/m²). Baseline BMI was associated with subsequent weight change irrespective of the antipsychotic given. Specifically, a smaller proportion of patients gained ≥7% baseline bodyweight, and a greater proportion of patients lost ≥7% baseline bodyweight with increasing baseline BMI. For olanzapine (the antipsychotic associated with highest mean weight gain in the total drug cohort), the percentage of patients gaining ≥7% baseline weight was 45% (95% CI: 43-48) in the underweight/normal weight BMI cohort and 20% (95% CI: 15-27) in the obese BMI cohort; 7% (95% CI: 6-8) of the underweight/normal cohort and 19% (95% CI: 13-27) of the obese cohort lost ≥7% baseline weight. BMI has an association with the likelihood of weight gain or loss and should be considered in analyses of antipsychotic weight change.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cohort Studies; Databases, Factual; Female; Global Health; Humans; Longitudinal Studies; Male; Middle Aged; Obesity; Olanzapine; Overweight; Prospective Studies; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Thinness; Weight Gain; Weight Loss

Numerous studies have demonstrated an association between bipolar disorder (BD) and obesity. However, these reports are limited by retrospective or cross-sectional designs, and the assessment of patients with lengthy illnesses. Prospective data, and data on weight gain early in the course of BD, are lacking.. We prospectively measured weight gain and laboratory metabolic indices over 12 months in 47 patients with BD receiving maintenance treatment following their first manic episode, and in 24 age- and gender-matched healthy subjects.. Although approximately two-thirds of patients had experienced previous depressive or hypomanic episodes, there was no difference between patients and healthy subjects in mean body mass index or rates of overweight or obesity at recovery from the first mania. Mean weight gain over 12 months was 4.76kg in patients and 1.50kg in healthy subjects (p=0.047). Combined rates of overweight and obesity at 6 months and 12 months exceeded 50% in patients, and were almost double those of healthy subjects. Logistic regression demonstrated that weight gain in the first 6 months was significantly associated with male gender and prescription of olanzapine or risperidone. Patients who were obese at 6 months and/or 12 months had significantly greater mean serum triglyceride levels and fasting glucose levels than non-obese patients.. This was a naturalistic study.. Even in patients with previous depressions and hypomanias, clinically significant weight gain in BD begins following the first manic episode, suggesting that it is primarily related to treatment with mood stabilizers and second-generation antipsychotics. However, the very small number of patients in our sample who were medication-free precludes a meaningful analysis of the degree to which weight gain might be an inherent feature of post-manic BD.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Cholesterol; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Insulin; Lithium Carbonate; Male; Obesity; Olanzapine; Overweight; Prospective Studies; Quetiapine Fumarate; Risperidone; Triglycerides; Valproic Acid; Weight Gain; Young Adult

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Child, Preschool; Dibenzothiazepines; Humans; Olanzapine; Overweight; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Weight Gain

Topics: Adult; Benzodiazepines; Birth Weight; Cohort Studies; Female; Follow-Up Studies; Humans; Infant, Newborn; Olanzapine; Overweight; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Young Adult

To investigate the feasibility of switching overweight schizophrenic patients to aripiprazole and to assess the impact of 12 months of aripiprazole treatment on weight in routine practice.. This was a non-controlled cohort study in overweight schizophrenic patients. Data were collected before treatment with aripiprazole was started and at 12-month follow-up.. A total of 53 patients were included; of these 55% continued using aripiprazole for 12 months. Aripiprazole treatment for 12 months (P = 0.027) and stopping clozapine or olanzapine treatment (P = 0.038) predicted weight loss (> or =3 kg). Patients receiving aripiprazole monotherapy (n = 16, mean -3.0 kg) had similar weight loss than patients receiving aripiprazole in addition to another antipsychotic drug (n = 13, mean -4.4 kg).. In routine practice once aripiprazole treatment was started, more than half of the patients remained on aripiprazole and most of them lost weight. Adding aripiprazole to clozapine gave similar weight loss as monotherapy with aripiprazole.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Cohort Studies; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Netherlands; Olanzapine; Overweight; Piperazines; Quinolones; Schizophrenia

A sample included 61 patients, 53 men and 8 women, with ICD-10 episodic schizophrenia in the remission after treatment with atypical neuroleptics (risperidon, olanzapine, clozapine). All patients were featured by therapeutically caused excess of body mass (obesity of different degrees) that hampered the further treatment. In 31 cases (the main group) atypical neuroleptics were substituted for traditional drugs that exerted lesser influence on body mass. Haloperidol (mean dosage 4,1 mg daily) was administered to 17 patients and trifluoperazine (mean dosage 7,1 mg daily) to 14 patients. Other 30 patients (a control group) continued to receive atypical neuroleptics. Between group differences of patient's mental and somatic state were assessed using quantitative scales. It was shown that the substitution of atypical neuroleptics for traditional neuroleptic drugs allowed to stop further body mass gain and even decreased it without significant influence on psychopathological symptoms and other side-effects in patients with excess of body mass.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Drug Prescriptions; Female; Follow-Up Studies; Haloperidol; Humans; Male; Mental Status Schedule; Olanzapine; Overweight; Risperidone; Schizophrenia; Treatment Outcome; Trifluoperazine

To assess the perceptions of clinicians in the psychiatric community about pharmacotherapy and its impact on weight gain and adverse metabolic effects in patients with bipolar disorder.. In November 2005, self-administered questionnaires were sent to 7000 psychiatrists who treat bipolar disorder in their clinical practice. An additional mailing of these questionnaires was sent in January 2006 to a different group of 7000 psychiatrists who treat bipolar disorder in their clinical practice. The first 298 completed surveys were analyzed.. Almost half of the respondents (48%) were psychiatrists in individual private practice and 32% were in community mental health centers. About two-thirds of respondents reported that 30-60% of their bipolar patients were overweight. Thirty-eight percent of respondents reported metabolic syndrome present in 20-40% of their patients. Almost all respondents (96%) reported a 20 lb increase in patients' weight as a troublesome potential adverse event associated with the use of some agents. After initiating a new medication, more than 80% of respondents monitored their patients' weight, fasting plasma glucose level, and fasting lipid profile at regular intervals. However, 80% did not monitor waist circumference. Overall, respondents viewed several agents (aripiprazole, ziprasidone, carbamazepine, and lamotrigine) as not (or minimally) problematic in terms of weight gain and adverse metabolic concerns. Clozapine and olanzapine were viewed as highly problematic due to their propensity to induce weight gain and negatively influence lipid and glucose metabolism. Other agents considered to be minimally to moderately problematic in terms of weight gain and metabolic issues were quetiapine, risperidone, lithium, and valproate. Respondents reported that the profile of a bipolar agent in terms of weight gain and adverse metabolic effects was an important consideration in the management of bipolar disorder.. Although the study is limited by a low response rate and self-selection of respondents, clinicians who did respond were concerned about the risks of weight gain and metabolic disturbances in their patients treated with bipolar agents. For most parameters, such concerns were being integrated into clinical care. However, it appears that there is a need to increase clinicians' appreciation of the importance of abdominal obesity and the need to monitor waist circumference. A growing recognition of the differences in weight-gain potential and adverse metabolic effects among agents appears to have had a definite impact on prescribing patterns in the management of bipolar disorder.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Clozapine; Female; Humans; Lipids; Male; Metabolic Syndrome; Olanzapine; Overweight; Perception; Practice Patterns, Physicians'; Weight Gain

Second generation antipsychotics (SGA) are obesitogenic and diabetogenic. Role of ghrelin (RIA), resistin and TNF-alpha (ELISA) in weight gain and insulin resistance (fasting plasma insulin, HOMA, ELISA) was studied in Hungarian psychiatryic patients (n=60) treated with SGA (clozapine, olanzapine, risperidone, quetiapine, 15 each). After 1 year, 80% of patients became overweight/obese (BMI > 27/30) and 35% (n= 21/60) presented impaired glucose tolerance (13/60) or diabetes (8/60). Ghrelin (1.3 +/- 0.6 ng/ml), resistin (9.8 +/- 3.7 ng/ml), TNF-alpha (5.8 +/- 1.7 pg/ml), insulin (10.4 +/- 7.6 U/ml, HOMA A: 2.5 +/- 1.8, HOMA B: 133 +/- 62.5) were significantly higher in patients than in healthy matched controls. Resistin and TNF-alpha positively correlated with each other, insulin, HOMA, and negatively with ghrelin. Ghrelin contributes to weight gain, resistin and TNF-alpha to insulin resistance. A negative feedback regulation may exist between adipocytokines and ghrelin production. SGA drugs enhance ghrelin production despite the suppressive effect of adipocytokines. All four SGA drugs are equally obesitogenic and diabetogenic.

Topics: Antipsychotic Agents; Benzodiazepines; Carbohydrate Metabolism; Case-Control Studies; Clozapine; Dibenzothiazepines; Female; Ghrelin; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Obesity; Olanzapine; Overweight; Peptide Hormones; Quetiapine Fumarate; Resistin; Risperidone; Tumor Necrosis Factor-alpha; Weight Gain