Antipsychotic drug treatment in first-episode mania: a 6-month longitudinal study

OBJECTIVE: To determine the use of antipsychotics during and following inpatient treatment of patients with a first-episode of mania. METHOD: The 198 subjects available for analysis were 129 consecutively hospitalized first-episode manic patients and 69 nonaffective psychotic patients assessed at admission and at 6-month follow-up postdischarge. Comparisons between the groups were made on frequency, type, and doses of antipsychotics prescribed during and after hospitalization in relation to clinical status. RESULTS: First-episode manic patients were given lower mean +/- SD daily doses of antipsychotics than nonaffective psychotic patients at discharge (163 +/- 132 mg chlorpromazine equivalents [CPZe] vs. 224 +/- 167 mg CPZe, p = .0102), at 6-month follow-up (109 +/- 167 mg CPZe vs. 260 +/- 178 mg CPZe; p = .0001), and if recovered (110 +/- 174 mg CPZe vs. 265 +/- 207 mg CPZe, p = .0014). At 6-month follow-up, 31 (24%) of 129 manic and 24 (35%) of 69 nonaffective psychotic patients continued to receive antipsychotics (NS). There was no difference between the groups in the time to discontinuation of antipsychotic agents. The mean time to drug discontinuation in manic patients was 98 days. CONCLUSION: (1) Antipsychotic doses at discharge and at 6-month follow-up were much lower in manic than in nonaffective psychotic patients, although there was no significant difference in the proportion of patients who continued to receive them 6 months after discharge. (2) The time to discontinuation was independent of clinical outcome. In those who discontinued the antipsychotic agent, the time to discontinuation was more rapid in the manic group than in the nonaffective psychotic patients.     

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

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

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.     

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.     

Olanzapine response in psychotic depression

BACKGROUND: Psychotic depression is more common than is generally realized, occurring in an estimated 16% to 54% of depressed patients. In controlled studies of patients with schizophrenia, the atypical antipsychotic olanzapine has been shown to be superior in efficacy to haloperidol at doses of 10 mg/day. Since olanzapine may have antidepressant effects in addition to its antipsychotic properties, the purpose of this study was to assess the safety and efficacy of olanzapine in the treatment of psychotic depression. METHOD: Hospitalized patients with the discharge diagnosis of DSM-IV psychotic depression (major depression with psychotic features or bipolar I disorder, depressed phase...with psychotic features) who had been treated with olanzapine during the first 9 months of its availability in the United States were identified. An age- and sex-matched sample of hospitalized patients with psychotic depression treated with other antipsychotics during the same time period was also identified. The medical records were expunged of all references to medication treatment and then reviewed and scored in a blind fashion for indications, doses, response, and side effects. RESULTS: Fifteen psychotic depression patients (10 women, 5 men), aged 36.9 +/- 10.1 years, who were treated with olanzapine were retrospectively compared with 15 psychotic depression patients (10 women, 5 men), aged 35.0 +/- 8.2 years, treated with other antipsychotics. Ten (67%) of 15 patients taking olanzapine were much or very much improved upon discharge compared with only 4 (27%) of 15 patients taking other antipsychotics (Fisher exact test, p = .037). Olanzapine was well tolerated: no patient discontinued the medication because of side effects. Twelve (80%) of 15 patients in each group were taking antidepressants in addition to the antipsychotic. Of the 3 patients taking olanzapine but not taking an antidepressant, 2 were much or very much improved (1 patient taking olanzapine alone, 1 taking olanzapine plus valproate sodium). CONCLUSION: Olanzapine appears to be effective and safe for patients with psychotic depression. Further prospective studies are warranted to ascertain whether olanzapine's unique pharmacologic profile may make it particularly useful for the treatment of psychotic depression either alone or in combination with antidepressants.     

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.     

Body weight gain after administration of antipsychotic drugs: correlation with leptin, insulin and reproductive hormones

Excessive body weight gain, hyperprolactinemia and low gonadal steroid serum levels are often observed during chronic administration of antipsychotic drugs (AP). Clinical and experimental findings suggest that leptin, the peptidic hormone involved in long-term body weight regulation, and reproductive hormones are interrelated. Therefore, we assessed circulating leptin levels in healthy, lean women (n = 12) and men (n = 7) before and after short-term administration of the AP sulpiride (SUL, 200 mg/day). In addition, we studied psychotic obese (n = 9) and lean women (n = 13) under chronic treatment with diverse AP. No significant weight changes were observed after SUL administration in healthy women--initial weight: 54.9+/-2.6 Kg; final weight: 55.04+/-2.6, NS. Leptin levels did not change either: 11.9+/-1.5 ng/ml. vs. 10.6+/-1.3, NS. By contrast, a small, but significant weight gain was found in SUL-treated men--60.6+/-1.9 Kg. vs. 61.3+/-2.1, p = 0.004. Leptin and insulin levels were significantly higher after SUL administration--leptin: 2.77+/-0.22 ng/ml. vs. 13.9+/-2.5, p=0.035; insulin: 3.59+/-0.17 mIU/ml vs. 8.81+/-0.81, p = 0.0001. In these subjects, leptin levels positively correlated with body weight change (p = 0.006), and serum prolactin change (p = 0.001). Obese psychotic women (Body Mass Index, BMI, Kg/m2 = 31.5+/-1.03) displayed higher leptin levels than non-obese psychotic women (BMI = 25.5+/-0.52): 26.8+/-4.8, vs. 12.8+/-3.4 ng/ml, p = 0.006. In these women, a significant positive correlation was found between leptin levels and BMI (p = 0.0001), and between leptin and basal insulin levels (p = 0.001). These results show that the expected circulating leptin elevation which is observed when body weight raises, is preserved in people treated with AP drugs.     

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.     

Bioactive lipids in schizophrenia

Bioactive lipids, in particular arachidonic acid (AA), are vital for monoaminergic neurotransmission, brain development and synaptic plasticity. Phospholipases A2 (PLA2) are key-enzymes in AA metabolism and are activated during monoaminergic neurotransmission. Reduced membrane AA levels, and an altered activity of PLA2 have been found in peripheral membranes of drug-na?ve patients with schizophrenia with some conflicting results in more chronic patient populations. Furthermore, in vivo brain phosphorus-31 magnetic resonance spectroscopy suggests reduced lipid membrane precursors (phosphomonoesters) and increased membrane breakdown products (phosphodiesters) in drug-na?ve or early treated first-episode schizophrenia patients compared to age-matched controls or chronic populations and these changes were correlated with peripheral red blood cell membrane AA levels. We postulate that processes modulating membrane lipid metabolism are associated with psychotic illnesses and might partially explain the mechanism of action of antipsychotic agents, as well as experimental agents such as purified ethyl-eicosapentaenoic acid (E-EPA). Recent supplementation trials suggest that E-EPA is a modestly effective augmentation treatment resulting in reduced doses of antipsychotic medication in acutely ill patients with schizophrenia (but not in residual-type schizophrenia). This review investigates the role of bioactive lipids in schizophrenia and its treatment, as well as its potential use in prevention.     

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: A longitudinal MRI study

BackgroundPituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations.AimsTo determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population.MethodPituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3 months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication.ResultsThere was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic (r = ? 0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses.ConclusionsAtypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.     

Length of psychiatric hospitalization and prediction of antipsychotic response

1. Clinical variables determining length of psychiatric hospitalization for psychotic inpatients were explored. Forty psychotic inpatients received a 14 day fixed dose neuroleptic trial. 2. Neuroleptic responders (25/40) were discharged 15 +/- 2 days after initiation of pharmacotherapy. For neuroleptic non-responders (15/40) antipsychotic medication was then altered as clinically indicated. Patients requiring one change in medication (N = 8) were discharged after 27 +/- 5 days; those requiring two medication adjustments (N = 4) were discharged after 33 +/- 3 days and those requiring three alterations in pharmacotherapy (N = 3) were discharged after 42 +/- 12 days. 3. Statistical analysis of clinical and diagnostic variables indicated that 84% of the variation in length of hospitalization was accounted for by the number of alterations in pharmacotherapy required for symptom remission and discharge. It is suggested that length of hospitalization may be decreased by decreasing the length of time a clinician prescribes pharmacotherapy that subsequently proves not effective. 4. Bayesian analysis was employed to identify the minimum length of pharmacotherapy which accurately predicts subsequent antipsychotic response/non-response. During the fixed dose neuroleptic trial response/non-response could be accurately predicted for 65% of the patients by Day 3 of the trial while by Day 7 response/non-response could be predicted for 80% of the patients. 5. The present data indicate that a three to seven day trial of antipsychotics may be sufficient for making pharmacotherapy decisions as such a trial demonstrates a diagnostic efficiency similar to other predictive tests employed in clinical medicine.     

Evaluation of subjective treatment satisfaction with antipsychotics in schizophrenia patients

Adherence to antipsychotic treatment is particularly important in the long-term management of schizophrenia and other related psychotic disorders since poor adherence to medication is associated with poor health outcomes. Although the patients' subjective satisfaction with the medication is crucial for adherence to medication, few studies have examined the relationship between subjective satisfaction with antipsychotics and adherence. In this study, we investigated subjective satisfaction with antipsychotics in patients with schizophrenia by using the Treatment Satisfaction Questionnaire for Medication (TSQM), a self-reporting instrument to assess the major dimensions of patients' satisfaction with their medication. The subjects included 121 clinically stabilized outpatients who met the following criteria: 1) patients between 20 and 65 years of age, diagnosed with schizophrenia or other psychotic disorders as defined by DSM-IV, 2) patients undergoing oral antipsychotic monotherapy or taking only an antiparkinsonian agent as an adjuvant remedy, and 3) patients who had received a stable dose of an antipsychotic for more than four weeks. Patients were asked to answer the TSQM questions, and their clinical symptoms were also evaluated by the Brief Psychiatric Rating Scale (BPRS). Satisfaction with regard to side-effects (p=0.015) and global satisfaction (p=0.035) were significantly higher in patients taking second-generation antipsychotics (SGAs, n=111) than those taking first-generation antipsychotics (FGAs, n=10), whereas no significant difference was found between the two groups in clinical symptoms according to BPRS (p=0.637) or the Drug-induced Extrapyramidal Symptoms Scale (DIEPSS, p=0.209). In addition, correlations were not significant between the subjective satisfactions and clinician-rated objective measures of the symptoms. These findings suggest that SGAs have more favorable subjective satisfaction profiles than FGAs in the treatment of schizophrenia. Since it is often difficult to detect the difference by a traditional objective assessment of the patients, it is desirable that physicians pay attention to the patients' subjective satisfaction in conjunction with their own objective clinical assessment.     

Are metabolic indices different between drug-naïve first-episode psychosis patients and healthy controls?

OBJECTIVE: To compare glucose and lipid metabolism parameters between drug-na?ve first-episode psychosis (FEP) patients with a diagnosis of schizophrenia spectrum disorder and healthy controls matched for age, ethnicity, and gender. METHOD: Baseline evaluations of fasting glucose and lipid metabolism parameters and the oral glucose tolerance test were performed with FEP patients (n=38), having no more than 10 days of cumulative exposure to antipsychotic medication, and normal community controls (n=36). Analysis of variance (ANOVA) was conducted to examine between group differences. RESULTS: FEP patients did not show a higher prevalence of the precursors to diabetes (impaired fasting glucose, impaired glucose tolerance, insulin resistance), and no significant difference in beta-cell function or lipid profile measures, compared to healthy controls. FEP patients showed a higher waist to hip ratio compared to controls. CONCLUSIONS: FEP patients having a schizophrenia spectrum disorder do not differ from healthy controls, in their baseline measures of glucose and lipid metabolites, nor in the prevalence of diabetes or its precursors, before (or close to) the onset of antipsychotic treatment.     

Diurnal weight gain in chronic psychosis

We found diurnal weight gain to be abnormal among 93 chronically psychotic patients, most of whom had schizophrenia. They were weighed at 7 a.m. and 4 p.m. weekly for 3 weeks. We normalized the diurnal weight gain (NDWG) as a percentage by subtracting the 7 a.m. weight from the 4 p.m. weight, multiplying the difference by 100, and dividing the result by the 7 a.m. weight. NDWG was 1.7 +/- 1.0 percent for the study sample, 0.6 +/- 0.4 percent for 16 acutely psychotic controls, and 0.5 +/- 0.4 percent for 29 normals. More than 60 percent of the study sample had abnormal NDWG values. NDWG related to antipsychotic drug dose (r = 0.290, p = 0.005) with variability in drug dose accounting for 8 percent of the variability in NDWG. This report provides yet another piece of evidence that disordered water balance is common in chronic psychiatric patients. The etiology is unknown, but it may relate to subtle brain abnormalities in the regulation of fluid intake and excretion.     

Sex, ethnicity, and antipsychotic medication use in patients with psychosis

Previous studies suggested that African American patients with psychotic disorders receive higher doses of antipsychotic medication than white patients, are more likely to receive depot antipsychotics, and are less likely to be prescribed second-generation antipsychotics. African-American men in particular may be most likely to receive excessive doses of antipsychotics and depot antipsychotics, although this is less clear. Few studies have examined how sex and ethnicity interactions affect treatment of psychotic disorders. In this study, we examined whether the interaction of sex and ethnicity predicted the use of depot antipsychotics and the dosing of antipsychotics in a sample of inpatients with psychotic disorders. The inpatient records of 167 patients with psychotic disorders were evaluated for type and dose of medication at discharge. African-American men received depot antipsychotic medication more frequently than African-American women and white patients. This difference persisted after controlling for sociodemographic and clinical variables. African-American men and women with psychotic mood disorders were also more likely to be discharged on high antipsychotic doses compared with white patients. There were no ethnic or sex differences in the dosing of antipsychotics for the treatment of schizophrenia spectrum disorders. There were also no ethnic or sex differences in the use of second-generation antipsychotics.     

Brain volume changes in first-episode schizophrenia: a 1-year follow-up study

BACKGROUND: Imaging studies of patients with schizophrenia have demonstrated that brain abnormalities are largely confined to decreases in gray matter volume and enlargement of the lateral and third ventricles. Global gray matter volume has been reported to progressively decrease in childhood-onset and chronic schizophrenia. Global gray matter volumes have not been examined longitudinally in patients with first-episode schizophrenia. One would expect global gray matter to decrease progressively, particularly in first-episode patients, because clinical deterioration is greatest in the early stages of the disease. METHODS: Patients with first-episode schizophrenia who had taken antipsychotic medication for 0 to 16 weeks (n = 34) and matched healthy comparison subjects (n = 36) were included in the study. For all subjects, magnetic resonance imaging scans of the whole brain were obtained at inclusion and after 1 year (mean [SD], 12.7 [1.1] months). Outcome was measured 2 years after inclusion. To compare morphological changes over time between patients and healthy comparison subjects, multiple repeated-measures analyses of variance were conducted with intracranial volume as a covariate. Outcome and cumulative antipsychotic medication were related to changes in patients' brain volumes. RESULTS: Total brain volume (-1.2%) and gray matter volume of the cerebrum (-2.9%) significantly decreased and lateral ventricle volume significantly increased (7.7%) in patients. The decrease in global gray matter volume significantly correlated with outcome and, independently of that, with higher cumulative dosage of antipsychotic medication. CONCLUSIONS: The loss of global gray matter in schizophrenia is progressive, occurs at an early stage of the illness, and is related to the disease process and antipsychotic medication.     

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.     

Failure of antipsychotic drug dose to explain abnormal diurnal weight gain among 129 chronically psychotic inpatients

1. The diurnal weight gain was found to be abnormal among 129 chronically psychotic inpatients. 2. The patients were weighed at 7 a.m. and 4 p.m. weekly for three weeks. We normalized the diurnal weight gain (NDWG) as a percentage by subtracting the 7 a.m. weight from the 4 p.m. weight, multiplying the difference by 100, and then dividing the result by the 7 a.m. weight. 3. NDWG was 2.2 +/- 1.5 percent for 87 male patients compared (p less than .0001) with .53 +/- .41 for 14 male controls. 4. NDWG was 1.8 +/- 1.0 percent for 42 female patients compared (p less than .0001) with .49 +/- .30 for 15 female controls. 5. Seventy percent of male and female patients had NDWG values greater than two standard deviations above the mean values of controls. 6. Differences in age, sex, morning weight, antipsychotic drugs, lithium, carbamazepine, phenytoin, blood pressure, and pulse did not explain these findings.