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.     

Differential effectiveness of clozapine for patients nonresponsive to or intolerant of first generation antipsychotic medications

This report examines whether the gains associated with changing to clozapine are greater for people who have been intolerant of first generation antipsychotic medications versus those who have been treatment-nonresponsive to previous agents. We examined data from an open-label, randomized trial that compared clozapine to usual care with first generation agents (n = 227). While most patients (n = 173, 76%) entered that study because they were nonresponsive to at least two first generation antipsychotic medications (treatment nonresponsive [TNR]), 24 percent (n = 54) were eligible because they experienced intolerable side effects (treatment intolerant [TI]). Significantly more TI patients discontinued their clozapine trial during the 2-year study compared to TNR patients, and TI patients taking clozapine were more likely to develop agranulocytosis or severe leukopenia. However, TI patients who remained on clozapine showed significant reductions in problematic behaviors and greater movement toward independent living situations than TNR patients. Clinicians should give serious consideration to offering clozapine and other second generation antipsychotic medications to patients who have demonstrated intolerance to first generation antipsychotic medications.     

Association of initial antipsychotic response to clozapine and long-term weight gain

OBJECTIVE: The aim of this study was to test whether the initial antipsychotic response to clozapine is related to subsequent weight change. METHOD: This study was an 8-year retrospective chart review of 96 hospitalized patients with schizophrenia. Data on monthly weight change, initial clinical response, age, gender, clozapine dose, and concomitant use of mood stabilizers and other antipsychotics were analyzed. RESULTS: Fifty-five (57.3%) of the patients received clozapine over the entire 8-year period; these subjects experienced an average weight gain of 11.7 kg (SD=1.6). Seventeen of these patients (30.9%) who had a significant initial clinical response (CGI improvement rating of 1 or 2 during the first 14 months) gained significantly more weight (13.8 kg [SD=8.4]) than did the 38 patients without a significant initial response (4.5 kg [SD=12.0]). Multiple linear regression analysis showed significant initial clinical response and lower baseline body mass index were associated with significantly more weight gain. CONCLUSIONS: The results show that initial antipsychotic response to clozapine is associated with subsequent long-term weight gain as measured over 8 years.     

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.     

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.     

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.     

Switching antipsychotics as a treatment strategy for antipsychotic-induced weight gain and dyslipidemia

Patients taking antipsychotic medications for psychiatric disorders also have many risk factors for medical comorbidities and early death. While these risk factors were present before the arrival of the newer antipsychotic medications, the overall risk factor burden is exacerbated for those high-risk patients whose antipsychotic therapy causes or aggravates obesity or dyslipidemia. Therefore, there is an urgent need for effective interventions to address problems related to the additional iatrogenic burden from weight gain and dyslipidemias caused by antipsychotic medications. For patients with schizophrenia, complete discontinuation of antipsychotic therapy is not advisable and, therefore, pharmacologic options are narrowed to dose adjustments, adding adjunctive agents to induce weight loss, discontinuation of other adjunctive agents associated with weight gain, or changing the antipsychotic medication ("switching"). This article reviews the evidence showing that relative to other possible treatment options, switching to an antipsychotic with a lower propensity to induce weight gain or dyslipidemia can be effective for reversing the weight gain and dyslipidemia caused by previous antipsychotic treatment.     

A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder

BACKGROUND: Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. METHOD: A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication. RESULTS: Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. CONCLUSION: These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.     

Topiramate in Bipolar and Schizoaffective Disorders: Weight Loss and Efficacy

BACKGROUND: Although useful in bipolar disorder, mood stabilizers, such as lithium, divalproex sodium, and carbamazepine, can cause significant weight gain. METHOD: We conducted a retrospective chart review of 5 patients with DSM-IV bipolar disorder or schizoaffective disorder who were treated with topiramate as adjunctive therapy or monotherapy. RESULTS: All 5 patients had a good response to treatment at a mean topiramate dose of 195 mg/day (range, 100-375 mg/day). All patients lost a substantial amount of weight on topiramate treatment. The average weight loss was 22 lb (10 kg; range, 8-56 lb [4-25 kg]). None of the patients discontinued topiramate because of side effects. CONCLUSION: Topiramate may represent a valuable alternative to existing mood stabilizers, either as an adjunct or as monotherapy in patients with bipolar disorder or schizoaffective disorder.     

Clozapine and hypertension: a chart review of 82 patients

OBJECTIVE: Clozapine has been linked to significant weight gain and increase in serum lipids and appears to negatively impact glucose metabolism. In this retrospective chart review study, we examine changes in systolic and diastolic blood pressure and treatment for hypertension in clozapine-treated patients. METHOD: Data on demographics and systolic and diastolic blood pressure were examined for up to 5 years (September 1987 to September 1992) in 82 patients treated with clozapine. Rates of hypertension treatment in clozapine-treated patients were compared with patients receiving conventional antipsychotics (N = 56) and other atypical antipsychotic agents (N = 102). RESULTS: The mean age of the 82 patients at the time of clozapine initiation was 36.4 +/- 7.8 years, with 22 (27%) female, 75 (91%) white, 3 (4%) black, 3 (4%) Hispanic, and 1 (1%) Asian. The baseline weight was 175.5 +/- 34.0 lb (79.0 +/- 15.3 kg) and baseline body mass index was 26.9 +/- 5.0 kg/m(2). There was a significant increase in systolic blood pressure (p =.0004) and diastolic blood pressure (p =.0001). Overall, 22 patients (27%) received treatment for hypertension following clozapine initiation. Only 2 (4%) of 56 patients in the conventional antipsychotic group and 9 (9%) of 102 patients in the other atypical antipsychotic group (olanzapine, N = 6; risperidone, N = 3) received treatment for hypertension. CONCLUSION: Our findings suggest that long-term clozapine treatment is associated with increased rates of hypertension, which may have a significant impact on medical morbidity and mortality.     

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.     

Weight gain with risperidone among patients with mental retardation: effect of calorie restriction

BACKGROUND: The atypical antipsychotics cause weight gain, which is poorly understood in terms of its mechanism and treatment. A usual recommendation for treatment of antipsychotic-induced weight gain includes calorie restriction and exercise. The authors describe their recent clinical experience with calorie restriction in adults with mental retardation treated with risperidone. METHOD: A retrospective chart review was performed on the records of 50 adult patients with mental retardation treated with risperidone while residing at a habilitation center. We assessed dose and duration of risperidone treatment, weight, changes in calorie intake, and frequency of aggressive behavior. RESULTS: Of the 50 patients, 39 had adequate data for analysis. Thirty-seven of the 39 patients gained weight with a mean of 18.8 lb (8.3 kg) over about 2 years. Twenty of the 37 patients were calorie restricted. Three of the 20 calorie-restricted patients lost weight at a rate of 0.2 lb (0.1 kg) per month. The other 17 calorie-restricted patients and the 17 patients who were not calorie restricted continued to gain weight at a rate of 0.8 lb (0.4 kg) per month over about another 2 years of treatment. The amount of weight gain was not dose related. Calorie restriction led to no deterioration in behavior. CONCLUSION: The current investigation lends support to data that note weight gain with risperidone in adults with mental retardation. It suggests that calorie restriction does not lead to weight loss or behavioral deterioration and that weight gain is not dose related.     

Incidence and costs of cardiometabolic conditions in patients with schizophrenia treated with antipsychotic medications

To examine the incidence of cardiometabolic conditions and change in care costs for patients with schizophrenia treated with antipsychotic medications, medical and pharmacy claims from the South Carolina Medicaid program were used to compare the incidence rates for five cardiometabolic conditions in 2,231 patients with schizophrenia who were newly prescribed one of seven antipsychotic medications, using a retrospective cohort design spanning three years. Incidence and cumulative prevalence (pre-existing + incident) rates for the five cardiometabolic conditions were: 10%/23.3% for Type II diabetes mellitus, 7%/13.3% for obesity/excessive weight gain, 17%/20.9% for dyslipidemia, 4.5%/7.3% for high blood pressure, and 15.6%/41.8% for hypertension. After being treated with the antipsychotic medications examined, the odds of developing obesity/excessive weight gain, Type II diabetes mellitus, or dyslipidemia were not significantly related to any specific atypical agent compared to haloperidol. Incidence rates for elevated blood pressure and clinically diagnosed hypertension were higher for patients prescribed ziprasidone (Odds Ratio [OR]=2.41, Confidence Intervals [CI]=1.20-4.85; OR=1.83, CI=1.16-2.90, respectively) relative to those prescribed haloperidol. Cost results indicate significant differences over time in medical service and pharmacy costs in the group which developed incident cardiometabolic conditions. Individuals diagnosed with schizophrenia with moderate prevalence and incidence rates for these cardiometabolic conditions demonstrated substantially decreasing medical care costs over the three years examined, perhaps indicating a widening gap in access to needed services for conditions that are known mortality risk factors.     

Novel antipsychotics: comparison of weight gain liabilities.

BACKGROUND: We performed a retrospective analysis of 122 clinical records of 92 male patients with DSM-III-R schizophrenia to examine the relative weight gain liabilities of clozapine, risperidone, olanzapine, and sertindole compared with haloperidol. We hypothesized that the unique pharmacodynamic profiles of these agents would contribute to different amounts and patterns of weight gain. METHOD: Data were analyzed to determine differences in weight gain during treatment among patients receiving 5 different drug treatments (clozapine [N = 20], olanzapine [N = 13], risperidone [N = 38], haloperidol [N = 43], and sertindole [N = 8]). Measures of maximal weight gain, final weight, and duration to maximal weight gain were calculated. RESULTS: Repeated measures analyses of variance controlling for age, treatment duration, and initial weight revealed statistically significant differences between groups on all 3 measures. Clozapine and olanzapine had the greatest maximal weight gain liability (F = 4.13, df = 4,23; p = .01). Weight gain with clozapine, but not olanzapine or risperidone, appears to persist (as reflected by final weight) despite behavioral interventions (e.g., nutritional consultation, suggested exercise regimen; F = 5.69, df = 4,23; p = .003). Clozapine- and olanzapine-treated subjects appeared to gain weight over a prolonged period of time, whereas risperidone-and sertindole-treated subjects had a more limited period of weight gain (F = 2.95, df = 4,25; p = .04). CONCLUSION: Clozapine and olanzapine caused the most weight gain, risperidone was intermediate, and sertindole had less associated weight gain than haloperidol. The relative receptor affinities of the novel antipsychotics for histamine H1 appear to be the most robust correlate of these clinical findings.     

Pharmacologic and nonpharmacologic strategies for weight gain and metabolic disturbance in patients treated with antipsychotic medications.

OBJECTIVES: To provide an overview of pharmacologic and nonpharmacologic strategies for antipsychotic-associated weight gain and metabolic disturbance, to identify important areas for future research, and to make practice recommendations based on current knowledge. METHODS: We undertook a selective review of interventions for weight gain and metabolic disturbance in the general population and in individuals treated with antipsychotic medications, focusing on randomized controlled trials in schizophrenia. RESULTS: Pharmacologic strategies include medication choice, medication dosage and formulation, choice of concomitant psychotropic medications, medication switching, medication addition to effect weight loss or prevent weight gain, and medications to increase insulin sensitivity. Medication choice and medication switching may have the most potent influence on weight and metabolic parameters. Modest short-term weight loss can occur with the addition of selective medications and (or) lifestyle interventions. However, more rigorous and longer-term studies are needed. CONCLUSIONS: Although difficult, the prevention of weight gain and the promotion of weight loss are possible for individuals treated with antipsychotic medications. Further research, including diabetes prevention studies, is required. We suggest a pathway for the management of weight gain and emerging metabolic disturbance.     

Retrospective Study of Olanzapine in Depressive and Anxious States in Primary Care

CONTEXT: Bipolar spectrum and treatment-resistant unipolar mood disorders are increasingly identified in primary care settings. Olanzapine demonstrates efficacy in the treatment of acute mania and bipolar depression and in bipolar maintenance therapy. Olanzapine-fluoxetine combination therapy shows efficacy in treatment-resistant depression. OBJECTIVE: To examine the efficacy and tolerability profile of olanzapine in various difficult-to-treat depressive and/or anxious states in primary care outpatients. METHOD: A retrospective chart review was conducted for all identifiable patients prescribed olanzapine for mood disorders (DSM-IV) during a 3-year period (July 1998-July 2001), utilizing clinician and nurse recall, sampling of general continuity clinic records, and a hand search of mood disorder clinic records. MAIN AND SECONDARY OUTCOME MEASURES: Initial and final scores on the Global Assessment of Functioning (GAF) scale, duration of therapy, and adverse effects. RESULTS: Thirty-seven patients were identified as having received treatment with olanzapine; 3 were referred to the mental health specialty sector at the time of treatment initiation, and 2 were lost to follow-up. Of the 32 patients receiving ongoing treatment by primary care clinicians, most were female (N = 23; 72%) and all were white (100%). Most were diagnosed with a mental illness in the bipolar spectrum (N = 25; 78%) and demonstrated treatment resistance with antidepressants and/or mood stabilizers (mean number of previous psychotropic medications = 3.7). In the group completing therapy (24 patients [75%]; mean duration of treatment = 242 days), GAF scores demonstrated a clinically and statistically significant improvement (mean initial GAF score = 59 +/- 9; mean final GAF score = 76 +/- 11; p < .0001). Twenty (83%) of these 24 patients demonstrated sustained improvement in their GAF scores. In the group that discontinued therapy (8 patients [25%]; mean duration of treatment = 123 days), GAF scores also demonstrated a clinically and statistically significant improvement (mean initial GAF score = 51 +/- 15; mean final GAF score = 70 +/- 11; p < .0001). Six (75%) of these 8 patients demonstrated sustained improvement in their GAF scores. For all patients, observed adverse effects included weight gain (25 patients [86%]; mean = 3.63 kg), sedation (6 patients [19%]), and dry mouth (1 patient [3%]). CONCLUSION: Olanzapine shows promise as an effective pharmacotherapeutic agent for primary care patients with mood disorders that lie along the bipolar spectrum or that are resistant to treatment with antidepressant monotherapies, but is associated with mild-to-moderate weight gain.     

Weight,lipids, glucose,and behavioral measures with ziprasidone treatment in a population with mental retardation

BACKGROUND: Atypical antipsychotics effectively reduce maladaptive behavior in individuals with mental retardation, yet bring significant weight gain and metabolic anomalies. Ziprasidone, a weight-neutral antipsychotic in patients with schizophrenia or schizoaffective disorder, has not been studied in a population with mental retardation and maladaptive behaviors. METHOD: Forty patients with mental retardation and maladaptive behaviors who had gained excessive weight or were inadequately responsive to other agents were switched to ziprasidone. Weight, total cholesterol, HDL, LDL, triglycerides, and frequency of maladaptive behavior were recorded at baseline and after 6 months of ziprasidone treatment. RESULTS: Ziprasidone treatment was associated with a significant weight loss of 8.1 lb (3.6 kg) as well as a significant reduction in total cholesterol and triglycerides (p < or =.05). The monthly frequency of the maladaptive behavior remained unchanged or improved in 72% (18/25) of the patients in whom maladaptive behavior was assessed. CONCLUSION: Ziprasidone effectively reduces the frequency of maladaptive behavior in a patient group with mental retardation without causing weight gain or metabolic disturbances.     

Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia

BACKGROUND: Patients with chronic schizophrenia (DSM-IV criteria) often receive depot antipsychotic medications to assure longer administration and better compliance with their treatment regimen. This study evaluated whether patients stabilized on depot antipsychotic medication could be successfully transitioned to oral olanzapine. METHOD: In a 3-month open-label study, 26 clinically stable patients with schizophrenia taking depot antipsychotics for over 3 years were randomly assigned to continue on their current depot dose or to switch to oral olanzapine. Clinical ratings (Positive and Negative Syndrome Scale [PANSS], Global Assessment of Functioning [GAF] scale, and Clinical Global Impressions [CGI] scale) and side effect parameters (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Scale, AMDP-5 scale, vital signs, and weight) were obtained monthly. RESULTS: Oral olanzapine patients (N = 13) demonstrated significant clinical improvement over the depot control group (N = 13) from baseline to 3-month endpoint (PANSS total, p =.012; PANSS general, p =.068; PANSS negative, p =.098; CGI-Improvement, p =.007; CGI-Severity, p =.026; GAF, p =.015). Side effect rating scales showed no statistical differences between the 2 groups (AIMS, Barnes Akathisia Scale, AMDP-5, vital signs). The depot control group showed no statistical superiority in any measure except weight change (p =.0005). After 3 months, all olanzapine patients preferred olanzapine to their previous depot medications and chose to continue on olanzapine treatment. CONCLUSION: Clinicians may expect clinical improvement when switching chronically psychotic patients from traditional depot antipsychotic drugs to oral olanzapine. Switching may be completed within a 4-week period with relative compliance being maintained and patients preferring oral olanzapine to their previous depot medications.     

Clozapine: weight gain in a pair of monozygotic twins concordant for schizophrenia and mild mental retardation

Clozapine is an atypical antipsychotic known to cause considerable weight gain. The extent to which genetic factors determine weight gain is unknown. Here we report on a pair of female monozygotic twins concordant for schizophrenia and mild mental retardation who were treated with clozapine over 5.5 years. One twin gained a total of 53.1 kg and had a weight of 107.5 kg (BMI=38.1 kg/m2) at the end of the observation period. The other twin gained a total of 48.2 kg and finally had a weight of 100.4 kg (BMI=33.8 kg/m2). Because both patients experienced considerable weight gain during treatment, our observation suggests that the antipsychotic-induced weight gain is under strong genetic control.