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.     

-759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment

5-HT2C receptor gene is viewed as an important candidate gene in pharmacogenetic studies of antipsychotic drug-induced weight gain. However, inconsistent results have been obtained in different populations. We investigated the association between the -759C/T polymorphism of the 5-HT2C receptor gene with early phase (after 4 weeks of treatment) weight gain induced by antipsychotic treatment in Korean schizophrenia patients. The study subjects were eighty-four in-patients receiving monotherapy with one of six antipsychotic drugs. Patients with the variant allele (-759T) were found to be less likely to have substantial (> 5%) weight gain (Fisher's exact test, p=0.030), and this association (t=1.91, df=75, p=0.030) was supported by the repeated measures analysis after controlling for possible confounding effects, i.e., age, sex, baseline BMI, and the type of antipsychotic medicine administered. The variant allele also appeared to have a protective effect against weight gain in a subgroup of patients receiving risperidone. These results support the involvement of the -759C/T polymorphism of the 5-HT2C receptor gene in antipsychotics-induced weight gain in the Korean population.     

Leptin concentrations are increased in subjects treated with clozapine or conventional antipsychotics.

BACKGROUND: Overweight is a considerable clinical problem in patients treated with antipsychotic agents. Recent results suggest that insulin resistance with increased insulin levels is also associated with treatment with the atypical antipsychotic agent clozapine. Leptin is important for the control of body weight and has been proposed to be a link between obesity and the insulin resistance syndrome. This study examined if clozapine-treated subjects and subjects treated with conventional antipsychotics had increased leptin levels compared with the general population and whether there was a gender difference in this respect. METHOD: Clozapine-treated patients (N = 41), patients treated with conventional antipsychotic drugs (N = 62), and healthy subjects from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) project (N = 189) were investigated with a cross-sectional study design. Weight, body mass index (BMI), and plasma leptin concentrations were measured, and all study subjects were investigated for the presence of diabetes mellitus. Drug treatment, health status, and smoking habits were registered. RESULTS: After adjustment for gender, BMI, smoking habits, age, and diabetes, hyperleptinemia was independently (p < .001) associated with clozapine treatment and with treatment with conventional antipsychotics (p < .005) within a multiple regression analysis. In separate multiple regression analyses, leptin levels were significantly associated with clozapine treatment in men (p = .002) and women (p =.023) and with conventional antipsychotic treatment in men (p = .027) but not in women. CONCLUSION: Treatment with clozapine as well as with conventional antipsychotics is associated with increased levels of circulating leptin. Hyperleptinemia can be an important link in the development of overweight and the insulin resistance syndrome in subjects receiving antipsychotic drugs, especially atypical agents like clozapine.     

Prevalence of overweight and obesity in bipolar patients

BACKGROUND: Patients who receive pharmacologic treatment for bipolar illness frequently gain weight. This study evaluated the prevalence of overweight and obesity in an unselected group of bipolar patients and matched reference subjects. METHOD: The prevalence of overweight, obesity, and central adiposity was evaluated in 89 euthymic bipolar (DSM-IV) patients and 445 reference subjects, matched for age and sex, using a cross-sectional study design. RESULTS: Female patients were more often overweight and obese than female reference subjects (chi2 = 9.18, df = 2, p = .01). The frequency of overweight was similar in male patients and male reference subjects, but male patients were more likely to be obese. Patients were more centrally obese than the general population in women (chi2 = 32.21, df = 1, p = <.001) and in men (chi2= 8.81, df = 1, p = .003). Patients treated with antipsychotic drugs were more obese than patients not receiving these drugs (chi2= 4.7, df = 1, p = .03). CONCLUSION: Body fat is more centrally distributed in pharmacologically treated bipolar patients than in matched population controls. Obesity is more prevalent in patients than in the general population. Obesity prevalence is clearly related to the administration of antipsychotic drugs.     

Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone

OBJECTIVE: Clinical factors predicting weight change in patients with schizophrenia and related disorders during acute treatment with the antipsychotic drugs olanzapine, risperidone, and haloperidol were sought through retrospective analyses. METHOD: Six-week body-weight data from 2 trials, study 1 comparing olanzapine and haloperidol (N = 1,369) and study 2 olanzapine and risperidone (N = 268), were analyzed. Effects of 8 clinically relevant covariates--therapy, clinical outcome (Brief Psychiatric Rating Scale), baseline body mass index (BBMI), increased appetite, age, gender, race, and dose--on weight were compared. RESULTS: In study 1, olanzapine (vs. haloperidol) therapy, better clinical outcome, lower BBMI, and nonwhite race significantly affected weight gain. Effects of increased appetite and male gender on weight gain were significant for olanzapine but not for haloperidol. In study 2, better clinical outcome, lower BBMI, and younger age significantly affected weight gain. Increased appetite was more frequent during olanzapine treatment than during haloperidol, but not significantly different from risperidone. Significant differences in effect on weight change were found between olanzapine and haloperidol but not between olanzapine and risperidone. No evidence was found that lower antipsychotic drug doses were associated with lower weight gain. CONCLUSION: This report identifies predictive factors of acute weight change in patients with schizophrenia. Similar factors across antipsychotic drugs in predicting greater weight gain included better clinical outcome, low BBMI, and nonwhite race. Factors differing between conventional (haloperidol) and atypical (olanzapine) agents included increased appetite and gender. Choice of atypical antipsychotic drug (olanzapine vs. risperidone) was of minor importance with regard to influence on acute weight gain.     

Newer antipsychotic drugs and obesity in children and adolescents. How should we assess drug‐associated weight gain?

OBJECTIVE: Antipsychotic drugs may contribute to weight gain in children and adolescents. METHOD: We used Medline's PubMed in the pediatric age using key words 'weight gain' and 'obesity', for each newer antipsychotic drug. RESULTS: We found 21 articles linking weight gain and obesity with newer antipsychotic drugs among youths. Risperidone was the most commonly cited agent. Weight gain from olanzapine was the largest among the more commonly prescribed newer agents. All studies reported absolute weight gain. Only a few studies used the better measure of body mass index (BMI). None incorporated growth charts to allow for changes in weight and height over time because of growth. CONCLUSION: Weight gain may be a major problem when prescribing newer antipsychotic drugs in the pediatric population. Risperidone is associated with less weight gain than olanzapine. Published reports and studies have not utilized state-of-the-art techniques using BMI with readily available growth charts.     

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.     

Weight gain and increase of body mass index among children and adolescents treated with antipsychotics: a critical review

We performed an updated review of the available literature on weight gain and increase of body mass index (BMI) among children and adolescents treated with antipsychotic medications. A PubMed search was conducted specifying the following MeSH terms: (antipsychotic agents) hedged with (weight gain) or (body mass index). We selected 127 reports, including 71 intervention trials, 42 observational studies and 14 literature reviews. Second-generation antipsychotics (SGAs), in comparison with first-generation antipsychotics, are associated with a greater risk for antipsychotic-induced weight gain although this oversimplification should be clarified by distinguishing across different antipsychotic drugs. Among SGAs, olanzapine appears to cause the most significant weight gain, while ziprasidone seems to cause the least. Antipsychotic-induced BMI increase appears to remain regardless of the specific psychotropic co-treatment. Children and adolescents seem to be at a greater risk than adults for antipsychotic-induced weight gain; and the younger the child, the higher the risk. Genetic or environmental factors related to antipsychotic-induced weight gain among children and adolescents are mostly unknown, although certain genetic factors related to serotonin receptors or hormones such as leptin, adiponectin or melanocortin may be involved. Strategies to reduce this antipsychotic side effect include switching to another antipsychotic drug, lowering the dosage or initiating treatment with metformin or topiramate, as well as non-pharmacological interventions. Future research should avoid some methodological limitations such as not accounting for age- and sex-adjusted BMI (zBMI), small sample size, short period of treatment, great heterogeneity of diagnoses and confounding by indication.     

Metabolic effects associated with atypical antipsychotic treatment in the developmentally disabled

OBJECTIVE: Atypical antipsychotics, especially clozapine and olanzapine, have been increasingly associated with weight gain and other adverse metabolic events (diabetes mellitus, hyperlipidemia) in non-mentally retarded populations. This report explores the incidence of this phenomenon in an institution-dwelling population of individuals with developmental disabilities. METHOD: A retrospective longitudinal analysis was performed for a sample of 41 adults with developmental disabilities and comorbid psychiatric and/or behavioral syndromes for whom treatment was converted from typical antipsychotics to olanzapine or risperidone for a minimum period of 2 years. Data were collected from October 1998 to September 2002. Among parameters analyzed were chlorpromazine equivalent dosage of antipsychotic, metabolic parameters, body mass index (BMI), level of concurrent medications, and concomitant dietary restrictions. RESULTS: Thirty-two study subjects (78.0%) were men. The mean age of the study subjects was 43.6 years (at the end of the study). Thirty-seven (90.2%) had severe-to-profound mental retardation. Eight (19.5%) were on a restricted diet. Twenty-three subjects (56.1%) were switched from a typical antipsychotic to olanzapine, and 18 subjects (43.9%) were switched from a typical antipsychotic to risperidone. Of the subsample of subjects who were switched from a typical antipsychotic to risperidone, 12 (66.7%) went on to be switched to olanzapine because of either emergent side effects or lack of efficacy. For the overall sample (N = 41), there was a 19.3% increase in chlorpromazine-equivalent antipsychotic dosage from baseline to the 2-year endpoint along with a 5.6% decrease in fasting blood glucose from baseline to the 2-year endpoint. There were no significant differences between baseline and endpoint values for BMI, total cholesterol, low-density lipoprotein cholesterol, or triglycerides. CONCLUSION: The findings of this 2-year evaluation suggest that clinically or statistically significant BMI increases as well as blood glucose and lipid elevations are not unavoidably correlated with the use of the atypical antipsychotic agents olanzapine and risperi-done and may be minimized by careful monitoring, a regimen of dietary control, and a moderate activity level in a residential population of individuals with mental retardation.     

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.     

Influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia: comparison of middle-aged and older adults.

OBJECTIVE: The authors investigated the influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia. METHODS: Subjects were 86 inpatients (mean age: 61.4 years) who had been receiving treatment with conventional antipsychotic drugs and who met DSM-IV criteria for schizophrenia. Their antipsychotic medication was changed from conventional antipsychotics to one of four atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, or risperidone). Patients were grouped by age (older or younger than 65 years). Subjective sleep quality and psychopathology were assessed twice: 1) at baseline, and 2) 8 weeks after switching to the atypical antipsychotic drugs. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the Positive and Negative Syndrome Scale (PANSS) was used to measure psychopathology. RESULTS: The proportion of the patients who experienced improved subjective sleep quality was significantly higher in the elderly than in the middle-aged group. Logistic-regression analysis revealed that the improvement in subjective sleep quality through administration of atypical antipsychotic drugs was predicted by increased age, daytime dysfunction, and longer sleep latency at baseline. CONCLUSION: These results demonstrate that atypical antipsychotic drugs are beneficial to the quality of sleep in elderly patients with schizophrenia.     

Weight gain with clozapine compared to first generation antipsychotic medications

Few studies have examined gender differences in the propensity to gain weight on clozapine. Weight gain increases risk for many medical illnesses and is of particular concern for people with schizophrenia who are more overweight than the general population. Long-stay patients in Connecticut state hospitals were randomly assigned to switch to open-label treatment with clozapine (n = 138) or to continue receiving first generation (conventional) antipsychotic medications (n = 89). Using survival and random regression models, we examined percentage of body weight gained during 2 years for patients assigned to clozapine versus those who continued taking first generation antipsychotic medications. We also examined the impact of gender on weight gain. Patients who switched to clozapine gained a greater percentage of weight (13 pounds, 7%) than did patients remaining on first generation medications (5 pounds, 4%) at the end of 2 years. Normal-weight patients on clozapine were more likely to become obese (body mass index [BMI] > or = 30). Patients gained weight whether they switched to clozapine or remained on first generation antipsychotic medications, but weight gain was significantly greater (1 BMI unit) in the clozapine-treated group, particularly among women.     

Relationship between obesity and antipsychotic drug use in the adult population: a longitudinal, retrospective claim database study in Primary Care settings

OBJECTIVE: To describe the association between obesity and the use of antipsychotic drugs (APDs) in adult outpatients followed-up on in five Primary Care settings. METHODS: A longitudinal, retrospective design study carried out between July 2004 and June 2005, in patients who were included in a claim database and for whom an APD treatment had been registered. A body mass index (BMI) <30 kg/m(2) was defined as obesity. The main measurements were: use of APDs, demographics, medical background and co-morbidities, and clinical parameters. Logistic regression analysis and ANCOVA with Bonferroni adjustment were applied to correct the model. RESULTS: A total of 42,437 subjects (mean age: 50.8 (18.4) years; women: 54.5%; obesity: 27.3% [95% confidence intervals (CI), 26.9%-27.7%]) were analyzed. A total of 1.3% of the patients were receiving APDs, without statistical differences in distribution by type of drug (typical: 48.8%; atypical: 51.2%). Obesity was associated with the use of APDs [OR = 1.5 (CI: 1.3-1.8)], hypertension [OR = 2.4 (CI: 2.2-2.5)], diabetes [OR = 1.4 (CI: 1.3-1.5)] and dyslipidemia [OR = 1.3 (CI: 1.2-1.4)], p < 0.0001 in all cases. BMI was significantly higher in subjects on APDs; 28.8 vs. 27.3 kg/m(2), p = 0.002, and remained higher after adjusting by age and sex (mean difference 0.4 (CI: 0.1-0.7), p < 0.01). After adjusting by age, sex and the Charlson index, obese subjects generated higher average annual total costs than nonobese subjects; 811 (CI: 787-835) vs. 694 (CI: 679-709), respectively, p < 0.001. CONCLUSIONS: Obesity was associated with the use of APDs, regardless of the type of drug, and with the presence of hypertension, diabetes and dyslipidemia. Obesity was also associated with substantially higher health care costs.     

Weight gain and metabolic effects of mood stabilizers and antipsychotics in pediatric bipolar disorder: a systematic review and pooled analysis of short-term trials

OBJECTIVE: To review weight and metabolic effects of mood-stabilizing treatments in pediatric bipolar disorder. METHOD: Systematic PubMed/Medline search of studies reporting on change in weight and/or glucose/lipid values with mood-stabilizing drugs in at least nine pediatric patients with bipolar disorder. RESULTS: Nineteen studies, including 24 medication trials in 684 patients (mean age, 12.3 +/- 2.9 years) were included. Youngsters received lithium, antiepileptics, or their combinations (n = 459), or second-generation antipsychotics, alone or combined with lithium or divalproex (n = 225), for 4 to 48 (mean, 15.4 +/- 12.7) weeks. Weight increase was significant/clinically relevant in 18 (75.0%) trials. Weight loss was significant with topiramate (2 studies, 38 subjects) and present with aripiprazole (1 study, 14 subjects). In trials lasting < or =12 weeks, weight gain was greater with second-generation antipsychotics plus mood stabilizers (5.5 +/- 1.8 kg) compared to mood-stabilizer monotherapy (1.2 +/- 1.9 kg, p <.05, Cohen's d = 2.33) or mood-stabilizer cotreatment (2.1 +/- 1.3 kg, p <.05, Cohen's d = 2.17), but not compared to antipsychotic monotherapy (3.4 +/- 1.3 kg, p >.05, Cohen's d = 1.34). Nonfasting glucose/lipid changes were nonsignificant in two second-generation antipsychotic trials (n = 61, 8.9%). CONCLUSIONS: Data are sparse regarding body composition effects and lacking for fasting metabolic effects of mood stabilizers in pediatric bipolar disorder. Combining antipsychotics with mood stabilizers seems to lead to greater weight gain than treatment with one or two mood stabilizers.     

Prevalence of and risk factors for tardive dyskinesia in a Xhosa population in the Eastern Cape of South Africa

OBJECTIVE: Despite prolonged use of antipsychotic drug treatment, the prevalence of tardive dyskinesia (TD) in a Xhosa population has not been evaluated. This study was undertaken to assess the prevalence and identify possible factors, including antioxidant intake and smoking history, which may increase or reduce the risk of TD. METHOD: One hundred two subjects who had been exposed to typical antipsychotic drugs for at least 6 months and were currently on an antipsychotic were screened for abnormal movements using the Abnormal Involuntary Movement Scale (AIMS) rating scale. Data about current and past antipsychotic therapy, diagnoses, smoking history, and dietary factors were gathered from the patient and from chart view. RESULT: Twenty-eight and four-tenths percent of subjects met criteria for tardive dyskinesia. Years of treatment and total cumulative antipsychotic dose were significant predictors of TD. Subjects with higher total consumption of foods containing antioxidants had lower rates of TD, but only consumption of onions was significantly associated with reduced prevalence. TD was less prevalent in smokers, but this difference did not reach statistical significance. Age, sex, and psychiatric diagnosis did not predict presence of TD. CONCLUSION: The result of this study indicate that TD in this population is more prevalent than previously believed within this local clinical context. Prolonged treatment and total antipsychotic drug exposure are important risk factors for TD in this population. Further study of the role of concurrent medications and dietary factors is indicated.     

Metabolic abnormalities in an early psychosis service: a retrospective, naturalistic cross-sectional study

Aim: There is an increasing recognition of the impact of weight gain on the development of metabolic abnormalities in young people receiving atypical antipsychotic drugs for first‐episode psychosis. This study examined the prevalence of such abnormalities in a specialist early‐intervention community mental health team. Methods: A retrospective case record audit of 85 patients 16–27 years old attending the Early Psychosis Service between October 2006 and June 2008, who had at least one metabolic measure defined as: weight, body mass index (BMI), waist circumference, blood pressure, and fasting blood glucose and lipids. Metabolic syndrome identified by the International Diabetes Federation (IDF) criteria. Results: Fifty‐five percent of males and 42% of females were overweight or obese at a median treatment duration of 8 months. Duration of antipsychotic therapy was associated with higher BMI (r = 0.28, P < 0.01). More than 40% of the total sample had high waist circumference. Of the 64 subjects with complete metabolic data, eight (12.5%) met full IDF criteria for metabolic syndrome, and another 21 (32.8%) had either increased waist with one metabolic abnormality or normal waist and two metabolic abnormalities. Conclusion: Over a third of young patients being treated for their first episode of psychosis either had metabolic syndrome or showed metabolic abnormalities. Treatment duration related to higher BMI and greater prevalence of metabolic syndrome. Detection of metabolic complications after treatment instigation in patients with first‐episode psychosis will permit early intervention with lifestyle or drug interventions in those at risk of significant physical health morbidity.     

Long-term topiramate treatment of psychotropic drug-induced weight gain: a retrospective chart review

OBJECTIVE: The objective of this study was to determine the efficacy and tolerability of long-term topiramate treatment of psychotropic drug-induced weight gain. METHOD: We conducted a retrospective review of the charts of patients treated with add-on topiramate in order to control weight gain induced by psychotropic drugs (antipsychotic drugs, lithium or valproate). RESULTS: The case series consisted of 100 patients. The mean final dose of topiramate was 186.8+/-138.3 mg/day, whereas the median dose was 200 mg/day for a total treatment duration of 41+/-38 weeks. Adverse events led to topiramate discontinuation in 22% of the sample. A significant reduction in body mass index was observed between the first and last measures, from 29.7+/-3.6 to 28+/-3.3 (t=5.82, P<.0005). The reduction in body mass index was greater in patients treated with antipsychotic drugs than in those treated with lithium or valproate alone. No difference was found between subjects with and those without comorbid active substance abuse or dependence. CONCLUSIONS: In this retrospective case series, topiramate was found to be effective in reversing weight gain associated with antipsychotic drugs, lithium or valproate. Tolerability of topiramate was an issue in some patients.     

Weight gain occurs after onset of bipolar illness in overweight bipolar patients.

BACKGROUND: Bipolar patients appear to have a risk of weight gain and obesity higher than the general population. This has traditionally been attributed to medication and disease variables, but there have not been any studies that have investigated this directly. METHODS: We examined 32 consecutive bipolar subjects and 32 matched controls for weight, BMI, fat content, and historic weight at age 18. RESULTS: Bipolar patients were heavier (193.1 +/- 55.6 vs. 165.6 +/- 37.8 lbs., P = 0.03), with greater BMI (30.3 +/- 8.8 vs. 24.3 +/- 4.0, P = 0.001), and higher fat content (33.3 +/- 9.9 vs. 19.1 +/- 9.9%, P < 0.0001) than psychiatrically well controls. A larger fraction of bipolar subjects were obese (BMI > 30, 50% vs. 9.7%, z = 3.88, P < 0.01). However, weight at age 18 was not statistically different (143.0 +/- 35.8 for bipolar subjects vs. 152.8 +/- 42.7 lbs., P = 0.3). CONCLUSIONS: This is the first controlled study examining weight gain in bipolar illness and the first demonstration that premorbid weight is in the normal range for bipolar subjects. Subsequent weight gain is probably related to illness and treatment variables.     

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.     

Obesity as a risk factor for antipsychotic noncompliance

OBJECTIVE: Weight gain is a common side effect of antipsychotic medications and is of particular concern with most of the newer "atypical" antipsychotics. It is, therefore, increasingly important to understand the impact of obesity and perceived weight problems on compliance with these medications. METHODS: A survey of treatment and health issues was mailed to local chapters of the National Alliance for the Mentally Ill (NAMI) and National Mental Health Association (NMHA), who distributed them to people with schizophrenia. Noncompliance was defined as a self-report of missing any antipsychotic medication in the previous month. The primary independent variables were (1) body mass index (BMI; weight [kg]/height [m2])-categorized as normal (< 25, n = 73), overweight (25-30, n = 104), or obese (> 30, n = 100)-and (2) subjective distress over weight gain. Other independent variables included demographics, medication attitudes, and treatment satisfaction. RESULT: BMI status and subjective distress from weight gain were predictors of noncompliance. Obese individuals were more than twice as likely as those with a normal BMI to report missing their medication (OR = 2.5; CI 1.1-5.5). A comprehensive model suggested that the primary mediator of noncompliance was distress over weight gain. CONCLUSIONS: There appears to be a significant, positive association between obesity and subjective distress from weight gain and medication noncompliance, even when accounting for other possible confounding factors.