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 associated with clozapine,olanzapine and risperidone in children and adolescents

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

Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment

OBJECTIVE: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. METHOD: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]). RESULTS: Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. CONCLUSIONS: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.     

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.     

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.     

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.     

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.     

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.     

Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder

OBJECTIVE: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period). RESULTS: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. CONCLUSIONS: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.     

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.     

Atypical antipsychotics and weight gain in Chinese patients: a comparison of olanzapine and risperidone

OBJECTIVE: To compare the effect of olanzapine with that of risperidone on weight change among Chinese patients in Hong Kong. METHOD: The body weight of subjects maintained on olanzapine or risperidone treatment was recorded at the outpatient clinic of a teaching hospital. Pretreatment weight of the subjects was retrieved from case records. Subjects on olanzapine treatment were matched in sex, age, and diagnosis with those on risperidone treatment, and demographic and clinical data were analyzed. The study was conducted in May and June 2002. RESULTS: Twenty-eight olanzapine-risperidone matched pairs were studied. All were diagnosed with DSM-IV schizophrenia. In patients treated with olanzapine and risperidone, respectively, mean +/- SD duration of treatment with atypical neuroleptics was 103.5 +/- 47.4 weeks and 93.2 +/- 50.6 weeks (range, 21-255 weeks), and mean doses were 12.4 +/- 6.7 mg/day and 4.5 +/- 2.8 mg/day. The mean +/- SD weight gain of subjects on treatment with olanzapine and risperidone, respectively, was 8.34 +/- 5.97 kg (18.53 +/- 13.27 lb) and 2.74 +/- 8.09 kg (6.09 +/- 17.98 lb) with a statistically significant difference at p < .005. Lower baseline body weight and body mass index were associated with greater weight gain in both olanzapine- and risperidone-treated subjects. Gender, age, mean daily dose, and duration of treatment had no effect on weight change. CONCLUSION: Treatment with olanzapine was associated with significantly greater weight gain than treatment with risperidone in Chinese schizophrenia patients in Hong Kong. The effect of adjunctive anticonvulsant treatment on weight gain requires further study.     

Olanzapine in refractory schizophrenia after failure of typical or atypical antipsychotic treatment: an open-label switch study

BACKGROUND: When patients with schizophrenia fail to respond to an atypical antipsychotic, they are sometimes switched to another atypical compound. However, the benefits of such a switch have not been adequately studied. We present an open-label prospective 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder whose treatment resistance to clozapine, olanzapine, risperidone, and haloperidol had been determined prospectively. METHOD: The subjects were 45 inpatients with DSM-IV schizophrenia or schizoaffective disorder who failed to respond to treatment during a 14-week double-blind trial comparing clozapine, olanzapine, risperidone, and haloperidol. The patients had been selected for participation in the double-blind trial on the basis of a history of suboptimal response to previous treatment. Inclusion criteria for the present study were (1) completion of at least 8 weeks of the 14-week double-blind trial, (2) treatment resistance to 1 of the 4 compounds tested as evidenced by a decrease in total PANSS score of less than 20%, and (3) total PANSS score > or = 60. Subjects were cross-titrated from the previous double-blind treatment to open-label olanzapine, 10 to 40 mg/day, and were treated for 14 weeks without concomitant psychotropic medication. Patients were evaluated weekly with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions scale, and Extrapyramidal Symptom Rating Scale. RESULTS: Open-label olanzapine treatment yielded no significant change in PANSS total, positive subscale, or negative subscale scores. There was a significant improvement for the PANSS cognitive factor (mean +/- SD change = 0.92 +/- 2.27; F = 7.5, df = 1,44; p <.009) and a marginally significant worsening for the excitement factor (mean change = -1.36 +/- 4.64; F = 4.0, df = 1,44; p < .053). Nine percent of patients (N = 4) were classified as responders using the Kane et al. criteria. The worsening in the PANSS excitement factor was significantly associated with the length of illness (t = -2.10, df = 44, p < .04). There was a nonsignificant decrease in extrapyramidal side effects and a significant increase in weight (mean increase = 3.5 +/- 6.2 kg [7.8 +/- 13.8 lb]; F = 5.29, df = 1,42; p <.0005). CONCLUSION: Our results indicate that in patients with treatment-resistant schizophrenia, a switch to olanzapine after treatment failure with an atypical agent or haloperidol may not reduce psychopathology in general, but may improve symptoms related to cognitive function.     

Service use and costs of treating schizophrenia with atypical antipsychotics

BACKGROUND: The high acquisition cost of the atypical antipsychotics has prompted their closer clinical and economic evaluation. This study aims to examine the financial implications of using atypical antipsychotics in a defined catchment area sample of patients with schizophrenia. METHOD: Service costs over a 10-month period were compared between groups of patients fulfilling DSM-IV criteria for schizophrenia who were taking different atypical antipsychotic agents. RESULTS: All patients studied were taking clozapine (N = 31). risperidone (N = 19), or olanzapine (N = 41). Clozapine was used in more chronic patients, while risperidone and olanzapine were prescribed in both chronic and recently diagnosed cases. After background group differences were controlled for, patients on risperidone treatment incurred the lowest costs. The monthly costs for the clozapine and olanzapine groups were higher than for risperidone by US $246 and US $566, respectively. CONCLUSION: Clozapine was reserved for more severe forms of schizophrenia, but its cost impact was relatively low. Risperidone, as prescribed in ordinary practice, may be more cost-effective than olanzapine.     

The effect of chronic treatment with typical and atypical antipsychotics on working memory and jaw movements in three- and eighteen-month-old rats

The effects of chronic treatment with typical and atypical antipsychotics on acquisition, working memory, motor activity, and rat tardive dyskinesia (TD) were studied in 3- and 18-month-old Sprague-Dawley rats. Acquisition and working memory were studied in eight-arm radial mazes. TD liability of antipsychotic drugs (APD) was evaluated in rat model of TD in which spontaneous repetitive jaw movements (RJM) occur during withdrawal from neuroleptic treatment. Motor behavior was assessed using the traverse beam test. D1 and D2 receptor occupancy was determined in the rat brain during treatment with typical and atypical antipsychotics. Chronic administration of clozapine, haloperidol, and risperidone impaired acquisition of the eight-arm radial maze in both young and aging rats while olanzapine had no effect. Retention tests showed that aging rats made more errors than the adults and that the antipsychotics haloperidol and risperidone significantly impaired retention in both age groups. Evaluation of motor behavior revealed that typical and atypical antipsychotics used in comparable doses in young rats had no effect on motor behavior, whereas in aging rats performance was impaired by clozapine, haloperidol, and risperidone but not by olanzapine. RJM responses were increased during washout from haloperidol treatment in young and aging rats whereas olanzapine, clozapine, and risperidone had no effect. D2 receptor occupancy in haloperidol- and risperidone-treated rats was above 70% while olanzapine and clozapine receptor occupancy was below 70%, which is the threshold for the appearance of extrapyramidal syndrome (EPS) and TD.     

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

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

EEG abnormalities during treatment with typical and atypical antipsychotics.

OBJECTIVE: Clozapine produces EEG abnormalities and dose-dependent risk of epileptic seizures. Much less is known about EEG effects of newer antipsychotics. The present study therefore examined the risk of EEG abnormalities associated with various antipsychotic drugs. METHOD: EEG recordings from 323 hospitalized psychiatric patients (293 treated with antipsychotics, 30 who did not receive any antipsychotic treatment) were graded blind to diagnosis and treatment for type and severity of EEG abnormalities. Drug type, dose, and clinical factors were evaluated for association with EEG abnormalities by multivariate logistic regression. RESULTS: EEG abnormalities occurred in 56 subjects (19.1%) treated and four (13.3%) not treated with antipsychotics. EEG abnormality risk among antipsychotic agents varied greatly (clozapine=47.1%, olanzapine=38.5%, risperidone=28.0%, typical neuroleptics=14.5%, quetiapine=0.0%). Significant risk factors in order of influence were hypertension, use of an atypical antipsychotic, bipolar diagnosis, and older age; benzodiazepine cotreatment lowered risk. Unassociated with risk were sex, treatment response, length of hospital stay, drug potency, daily dose (in mg or mg/kg), drug exposure time, or cotreatments. CONCLUSIONS: EEG abnormality risk varied widely among specific antipsychotics. Risk was particularly high with clozapine and olanzapine, moderate with risperidone and typical neuroleptics, and low with quetiapine. Comorbid hypertension, bipolarity, and older age-but not dose or clinical response-were associated with risk.     

Clinical drug monitoring in child and adolescent psychiatry: side effects of atypical neuroleptics

OBJECTIVE: The aim of this study was to improve and evaluate the practibility of a method for the assessment of drug-associated side effects, and we implemented a clinical drug monitoring for atypical neuroleptics. METHODS: Side effects of initially hospitalized patients treated with clozapine (n = 16), olanzapine (n = 16), and risperidone (n = 19) were prospectively monitored on a weekly basis for the first 3 weeks. In the case of stable medication, measurements of all variables were made every 4 weeks or upon discharge. We used the Dosage Record Treatment Emergent Symptom Scale (DOTES) in a supplemented version to measure the presence and severity of side effects. RESULTS: Drowsiness and decreased motor activity were common, especially in the first 2 weeks. Orthostatic hypotension, increased salivation, constipation, and nasal congestion were seen in more than 30% to 60% of patients treated with clozapine and were less common in adolescents treated with olanzapine and risperidone. Rigidity, tremor, and dystonia were seen in 5% to 15% of patients treated with risperidone and olanzapine. The average weight gain after 6 weeks of treatment with the atypical neuroleptics was significantly higher for the olanzapine group (4.6 +/- 1.9 kg) than for the risperidone (2.8 +/- 1.3 kg) and clozapine (2.5 +/- 2.9 kg) groups. CONCLUSIONS: The authors' supplemented DOTES version is generally applicable to clinical use in mental health centers. The differences among the side effects of these three agents may affect compliance with medication and medical risks of metabolic syndrome, diabetes, and cardiovascular disease. More research on the short- and long-term safety of psychotropic drugs in children and adolescents, using standardized methods, should be considered.     

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.     

Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic

BACKGROUND: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. METHOD: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.     

抗精神病药对精神分裂症患者体重的影响

目的 为了探讨抗精神病药对精神分裂症患者体重的影响。方法 295例服用抗精神病药的精神分裂症患者进行了临床调查。结果 67．12％患者出现体重增加；体重增加从多到少的药物依次是氯氮平、奥氮平、氯氮平合并利培酮、氯丙嗪、利培酮、氯氮平合并舒必利；氯氮平、氯丙嗪、利培酮体重增加较人组前有显著差异；女性患者、初次服抗精神病药者、合并心境稳定剂者体重增加亦明显。结论 大部分抗精神病药可导致体重增加，应在治疗前及治疗中定期进行体重监测。