Twenty-Four-Hour Measures of Heart Rate-Corrected QT Interval, Peak-to-End of the T-Wave, and Peak-to-End of the T-Wave/Corrected QT Interval Ratio During Antipsychotic Treatment.

PURPOSE/BACKGROUND: Prolonged ventricular repolarization, measured by heart rate-corrected QT interval (QTc) prolongation, might be a biomarker for risk of torsade de pointes (TdP) and sudden cardiac death. However, the predictive value of QTc has been challenged, and a component of QTc, peak-to-end of the T-wave (Tpe), and a high Tpe/QT ratio might be superior biomarkers because they better reflect increased transmural dispersion of ventricular myocyte repolarization, which can lead to TDP. The purpose of this pilot study was to provide the first measurements of heart rate, QTc, Tpe, Tpe/QTc, and their variability over 24 hours in medication-free patients with schizophrenia, during treatment with ziprasidone or other antipsychotic drugs, and healthy controls. METHODS: Subjects included 12 patients treated with ziprasidone, 30 treated with other antipsychotic drugs, 3 unmedicated patients, and 15 normal controls. Subjects underwent 24-hour analog Holter recording, and the recordings were digitized. A cardiologist blind to treatment selected multiple 10-cycle segments throughout each recording and measured the electrocardiogram metrics. RESULTS: Variability in QTc, Tpe, and Tpe/QTc over the 24 hours was present in all groups; 91.1% of patients and 100% of controls had 1 or more QTc values of 450 milliseconds or greater. Mean QTc length was significantly greater in the ziprasidone-treated than the non-ziprasidone-treated patients (P = 0.02). Mean Tpe was not elevated in the ziprasidone patients, whereas mean Tpe/QTc was lower (P < 0.01). CONCLUSIONS: The large variability in QTc, Tpe, and Tpe/QTc observed supports the need for 24-hour electrocardiogram recordings to provide an accurate assessment of risk of TdP. Heart rate-corrected QT interval alone does not capture the risk of TdP.

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia.

OBJECTIVES: We tested the hypothesis that a common functional variant in brain-derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic-induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high- and low-density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested. METHODS: This was a 12-month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76). RESULTS: BMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log-triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01). CONCLUSIONS: The positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well.

Prevalence and risk factors of psychotic symptoms: in the city of Izmir, Turkey.

BACKGROUND: Psychotic symptoms, psychotic-like experiences and schizotypal signs can emerge in different socio-cultural circumstances and cause clinical or non-clinical pictures. Transient or self-limiting psychotic-like experiences are more prevalent than clinical psychotic disorders. The aim of this study is to determine the prevalence and sociodemographic correlates of psychotic symptoms in an urban area. METHODS: A cross-sectional study was conducted among the residents of two districts in the urban area of Izmir, Turkey. Among the systematically selected 1,500 residents of 85,212-study population, a total of 1,268 individuals (response rate: 84.5%) were screened for any lifetime psychotic symptoms. RESULTS: Composite International Diagnostic Interview (CIDI) was used to assess psychotic symptoms. CIDI (+) psychotic symptoms were found in 3.6% of the screened sample. Logistic regression analysis showed that being a female (OR=2.4, 95% CI=1.2-5.1), having a first degree family history of any mental disorders (OR=13.9, 95% CI=5.7-34.3), lack of social support (OR=4.5, 95% CI=2.3-8.6) and alcohol use (OR=4.9, 95% CI=2.3-10.6) were all related to psychotic symptoms. CONCLUSION: Prevalence of any psychotic symptom is lower compared to European studies. Alcohol might be considered as a risk factor for developing psychotic symptoms in the Turkish cultural setting.

Panic symptoms in schizophrenia: comorbidity and clinical correlates.

The aim of the present study was to investigate the prevalence of panic attack (PA) and panic disorder (PD) in patients with schizophrenia and detect the clinical features. Forty-nine patients with schizophrenia were included in the study. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), Extrapyramidal Symptom Rating Scale (ESRS) and Bandelow Panic and Agoraphobia Rating Scale were administered. Fifteen patients were found to have PA and seven patients had PD. Patients with panic symptoms had higher scores of PANSS, HDRS, CGI and ESRS. Comorbid panic symptoms in schizophrenia may be related to positive symptoms, extrapyramidal side-effects and depression.

A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.

BACKGROUND: Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy. METHOD: This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003. RESULTS: Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group. CONCLUSION: Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.

A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety.

BACKGROUND: Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine. The purpose of this study was to carry out a placebo-controlled, randomized, double-blind trial of the efficacy, safety, and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine. METHOD: In this 6-week double-blind study, 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were randomly assigned to risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale, the Clinical Global Impressions-Severity of Illness scale, the Global Assessment of Functioning scale, and the Quality of Life Scale. A variety of safety and tolerability measures were also obtained. Data were collected between November 2001 and July 2003. RESULTS: Significant improvement was noted in both groups on a variety of measures of psychopathology, but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure, the PANSS positive symptom subscale. There were no significant differences between the treatment groups regarding extrapyramidal symptoms, weight gain, vital signs, serum clozapine levels, and QTc interval. The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation. The patients treated with risperidone developed significant increases in plasma prolactin levels. CONCLUSION: Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period.

Effect of clozapine on serum leptin, insulin levels, and body weight and composition in patients with schizophrenia.

OBJECTIVE: Weight gain frequently occurs during treatment with clozapine. However, the pathophysiology of clozapine-induced weight gain remains unclear. The aim of this study was to investigate the influence of clozapine on hormones leptin and insulin in relation to body weight and composition measures to determine their contribution to clozapine-induced weight gain. METHOD: Data are reported on 19 patients with schizophrenia (11 women and 8 men) who completed 10 weeks of treatment with clozapine. Insulin levels, weight measurements, body mass index (BMI), and body composition measurements were evaluated at baseline and at the end of treatment. Leptin levels were assessed at baseline and after 4 and 10 weeks of treatment. Analysis of variance with repeated measures was used to evaluate changes in weight, body composition measures, leptin, and insulin. The Pearson correlations were used to assess the relationships between changes in hormone levels and weight along with body composition measurements. The correlations of change in Positive and Negative Syndrome Scale (PANSS) score with changes in hormone levels, weight gain and body composition measures were evaluated with Pearson correlations. RESULTS: Leptin and insulin levels did not show any significant alterations across time. The use of clozapine was associated with significant increases in BMI (F=19.8, P<.001), lean muscle mass (F=8.2, P=.01), and fat mass (F=15.4, P=.001), while total body fluid percentage (F=4.1, P=.05) significantly decreased. Improvement in PANSS scores was not correlated to change in leptin, insulin, weight, BMI, or body composition measurements. The change in leptin levels was correlated to change in body fat mass. CONCLUSION: The role of leptin in weight gain induced by clozapine might be a regulatory mechanism rather than being etiologic.