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Biomedical subjects

Jean-Pierre Lindenmayer

Publications and source records attributed to Jean-Pierre Lindenmayer.

At least 19 recordsLinked to original sources
PubMed2006

Long-term safety and tolerability of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder.

Subjects were patients with schizophrenia or schizoaffective disorder enrolled in extension studies (Study A and Study B) after participating in 12-week studies of long-acting injectable risperidone [Kane, J.M., Eerdekens, M., Lindenmayer, J.-P., Keith, S.J., Lesem, M., Karcher, K., 2003. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am. J. Psychiatry 160, 1125-1132; Lindenmayer, J.-P., Eerdekens, L., Berry, S., Eerdekens, M., 2004. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J. Clin. Psychiatry 65, 1084-1089]. Twelve months of treatment were completed by 55% of Study A patients and 52% of Study B patients. The median modal dose of long-acting injectable risperidone was 50 mg/14 days in both studies. Most frequent adverse events were psychosis, headache, insomnia, agitation, and rhinitis. EPS-related adverse events were reported in 33% of patients in Study A and 22% in Study B. Patients with Clinical Global Impressions ratings of "not ill" and "mild" increased from 14% at baseline to 54% at endpoint in Study A and from 42% to 65% in Study B. It is concluded that treatment with long-acting injectable risperidone for 1 year or longer appeared to be safe and well tolerated in patients with schizophrenia or schizoaffective disorder.

Adolescent↗
PubMed2006

Aggression and quantitative MRI measures of caudate in patients with chronic schizophrenia or schizoaffective disorder.

Caudate dysfunction is implicated in schizophrenia. However, little is known about the relationship between aggression and caudate volumes. Forty-nine patients received magnetic resonance imaging scanning in a double-blind treatment study in which aggression was measured. Caudate volumes were computed using a semiautomated method. The authors measured aggression with the Overt Aggression Scale and the Positive and Negative Syndrome Scale. Larger caudate volumes were associated with greater levels of aggression. The relationship between aggression and caudate volumes may be related to the iatrogenic effects of long-term treatment with typical antipsychotic agents or to a direct effect of schizophrenic processes on the caudate.

Adult↗
PubMed2005

Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder.

The relationship between orbitofrontal cortex (OFC) volumes and functional domains in treatment-resistant patients with schizophrenia or schizoaffective disorder is poorly understood. OFC dysfunction is implicated in several of the behaviors that are abnormal in schizophrenia. However, little is known about the relationship between these behaviors and OFC volumes. Forty-nine patients received magnetic resonance imaging scanning as part of a double-blind treatment study in which psychiatric symptomatology, neuropsychological function, and aggression were measured. OFC volumes were manually traced on anatomical images. Psychiatric symptomatology was measured with the Positive and Negative Syndrome Scale (PANSS). Aggression was measured with the Overt Aggression Scale (OAS) and with the PANSS. Neuropsychological function was assessed using a comprehensive test battery. Larger right OFC volumes were associated with poorer neuropsychological function. Larger left OFC gray matter volumes and larger OFC white matter volumes bilaterally were associated with greater levels of aggression. These findings are discussed in the context of potential iatrogenic effects.

Adult↗
PubMed2005

Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia.

G-proteins are composed of alpha, beta and gamma subunits. Once activated, these subunits play a major role in the conversion of external receptor activation into intracellular signals. The functional C825T polymorphism of the beta3 subunit gene (GNB3) has recently been shown to modulate antidepressant response, with the T-allele conferring an increased signaling and being associated with favorable antidepressant response. We hypothesized that this polymorphism may be associated with response to antipsychotics in a population of 145 chronic schizophrenic patients deriving from two study-samples and being mainly treated with clozapine for up to 6 months. Overall, the C/C genotype was significantly associated with relative clinical improvement as measured by Brief Psychiatric Rating Scale (BPRS) change scores after 6 and 12 weeks (p<0.01 and p=0.03, respectively), with estimated effect sizes ranging from 4.8 to 7%. Our results further suggest that this effect is only attributable to Caucasians when compared to African-Americans. Moreover, our findings point to the role of intracellular mechanisms in antipsychotic response.

Adult↗
PubMed2005

The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia.

The synaptosomal-associated protein of 25 kDa (SNAP-25) is an essential component of the core complex that mediates presynaptic vesicle trafficking. Thus, SNAP-25 is directly involved in the release of neurotransmitters. Quantitative alterations of SNAP-25 expression have been reported in brain regions and cerebrospinal fluid (CSF) of schizophrenics and in haloperidol treated rats. This observed altered expression may be influenced by genetic variants of SNAP-25. We hypothesized that polymorphisms of the SNAP-25 gene (sites DdeI, MnlI and TaiI in the 3'UTR) are associated with antipsychotic drug response and induced weight gain. A sample of 59 patients with prior suboptimal response to antipsychotic treatment and diagnosed with DSM-IV schizophrenia or schizoaffective disorder was examined. Patients were administered clozapine, haloperidol, olanzapine or risperidone for up to 14 weeks. Clinical response was defined as the difference between the baseline and the endpoint total scores on the Positive and Negative Syndrome Scale (PANSS). Weight was assessed at baseline and at study endpoint. ANOVA revealed that the MnlI and TaiI polymorphisms were associated with response (F[2,53] = 4.57, p = 0.01 and F[2,52] = 3.53, p = 0.03) and with weight gain (F[2,52] = 4.28, p = 0.01 and F[2,51] = 3.38, p = 0.04). When covariates were included, the MnlI polymorphism remained significantly associated with changes of PANSS scores, but not with weight gain. The DdeI polymorphism was not associated with response or weight gain. These findings suggest that SNAP-25 gene variants affect clinical response in patients with prior poor response to antipsychotics. Weight changes do not seem to be associated with polymorphism of the SNAP-25 gene, however, replication in independent samples is warranted.

Adult↗
PubMed2005

Aggression and psychopathology in treatment-resistant inpatients with schizophrenia and schizoaffective disorder.

Positive psychotic symptoms, such as threat/"control-override" delusions or command hallucinations, have been related to aggression in patients with schizophrenia. However, retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior. In this study, we monitored aggressive behavior and psychopathology prospectively and in close temporal proximity in 157 treatment-resistant inpatients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial. Aggressive behavior was rated with the overt aggression scale (OAS). Psychopathology was assessed using the positive and negative syndrome scale (PANSS). At baseline, subjects who would be aggressive during the study had higher scores on only two PANSS items: hostility and poor impulse control. During the study PANSS positive subscale scores were significantly higher in aggressive subjects. Total PANSS scores were higher within 3 days of an aggressive incident, as were positive and general psychopathology subscale scores. However, in a smaller subsample for whom PANSS ratings were available within 3 days before aggressive incidents, only scores on the PANSS positive subscale were significantly higher. These findings in chronic, treatment resistant inpatients support the view that positive symptoms may lead to aggression.

Aggression↗
PubMed2005

Identification of a naturally occurring 21 bp deletion in alpha 2c noradrenergic receptor gene and cognitive correlates to antipsychotic treatment.

Neurocognitive deficits are recognized as a cardinal feature of schizophrenia. Atypical antipsychotics have high affinity for many neurotransmitter receptors. Among these receptors, antipsychotics are antagonists of adrenoceptors, and this pharmacological property has been postulated to be involved in the mechanism of action of antipsychotics. We tested the hypotheses that clinical response and cognitive improvement to antipsychotic treatment are associated with genetic variation in adrenergic alpha2C receptor (ADRA2C). Fifty-seven patients with chronic schizophrenia were prospectively assessed for clinical response to antipsychotic treatment. They were subsequently genotyped for a 21 bp insertion/deletion that we identified in the 3' untranslated region (3'UTR) of ADRA2C. With regard to clinical response and cognitive improvement to antipsychotics, there was no significant association observed for this polymorphism. Our results suggest that the novel polymorphism may not play a major role in antipsychotic response.

Alleles↗
PubMed2005

Clozapine, risperidone, olanzapine, and conventional antipsychotic drug effects on glucose, lipids, and leptin in schizophrenic patients.

Some reports have indicated increased rates of diabetes and increased prevalence of glucose and lipid abnormalities during treatment with second-generation antipsychotics, with most concern raised about clozapine and olanzapine. Most of the findings have come from case reports, retrospective examination of laboratory values, and analysis of health-care claims databases. This study investigated fasting levels of glucose, lipids, and leptin in a non-randomized, cross- sectional study of 210 patients, with schizophrenic or schizoaffective disorder, treated with a single antipsychotic medication - clozapine, risperidone, olanzapine, or a conventional antipsychotic. Glucose tolerance tests (GTT), with a 75-g glucose load, were preformed in a subset of patients. In this sample most mean fasting glucose and lipid levels were within the normal range and were not significantly different across the four drug treatment groups. Patients treated with clozapine and olanzapine had higher triglyceride levels than risperidone patients. In patients receiving a GTT, risperidone-treated patients had higher glucose levels at 1 h than patients treated with olanzapine, and there were more patients on risperidone who met American Diabetes Association glucose metabolic criteria for diagnosis of diabetes. Although there were no significant differences in age or body mass index among the four drug groups, we cannot rule out some potential biasing factors we did not assess which could potentially influence our results. These include unknown physician preference in drug selection based on their beliefs about the weight-inducing or diabetes potential of different antipsychotics, differences in visceral fat, and differences in patients' antipsychotic drug history.

Adult↗
PubMed2005

Minimal injection site pain and high patient satisfaction during treatment with long-acting risperidone.

Long-acting injectable antipsychotic formulations of conventional antipsychotics were developed to address the problem of partial adherence among patients with schizophrenia. Injection site pain, other skin reactions and patient satisfaction with treatment were assessed in two large, multicentre studies of long-acting injectable risperidone (Risperdal CONSTA, Janssen Pharmaceutica Products, Titusville, New Jersey, USA), the first available long-acting atypical antipsychotic agent. Patients rated injection site pain using a 100-mm Visual Analogue Scale (VAS), and investigators rated injection site pain, redness, swelling and induration. Patient satisfaction with treatment was assessed with the Drug Attitude Inventory (DAI). VAS pain ratings were low at all visits across all doses in both studies, and decreased from first to final injection. In the 12-week, double-blind study, mean +/- SD VAS scores at the first and final injections were 15.6 +/- 20.7 and 12.5 +/- 18.3 for placebo-treated patients, and 11.8 +/- 14.4 (first) and 10.0 +/- 12.4 (final) for 25 mg; 16.3+/-21.9 (first) and 13.6 +/- 21.7 (final) for 50 mg; and 16.0 +/- 17.9 (first) and 9.6 +/- 16.0 (final, P<0.01) for 75 mg of long-acting risperidone. Mean VAS scores in the 50-week, open-label study at the first and final injection were: 17.9 +/- 22.2 (first) and 9.5 +/- 16.7 (final, P<0.0001) for 25 mg; 18.1 +/- 19.7 (first) and 10.4 +/- 14.8 (final, P<0.0001) for 50 mg; and 18.5 +/- 21.6 (first) and 13.6 +/- 19.9 (final, P = 0.0001) for 75 mg of long-acting risperidone. Overall, there was no or minimal injection site pain and skin reactions were rare. Mean DAI ratings were available for the 50-week study and indicated high patient satisfaction throughout the trial (baseline = 7.30; endpoint = 7.70; P<0.0001 versus baseline). These findings may positively affect patient and clinician attitudes towards long-term therapy with long-acting injectable risperidone.

Adult↗
PubMed2005

Dosing of quetiapine in schizophrenia: how clinical practice differs from registration studies.

BACKGROUND: A substantial number of patients with psychosis receive quetiapine in amounts that are greater than what is recommended in the product labeling approved by drug regulatory agencies. The purpose of this article is to review the past and present dosing patterns of quetiapine for the treatment of schizophrenia. METHOD: A PubMed search for the period January 1, 1990, to July 1, 2005, was conducted to identify English-language articles related to quetiapine dose in schizophrenia using the search terms quetiapine, dose, and schizophrenia. Trends in dosing of quetiapine in a large, state-operated psychiatric hospital system and the anecdotal evidence describing the use of quetiapine in excess of 800 mg/day were also reviewed. RESULTS: The registration studies of quetiapine suggest a target dose range of 300 to 500 mg/day for schizophrenia. In contrast, among inpatients hospitalized in New York State in the period of April 1, 2004, to June 30, 2004, the mean dose of quetiapine prescribed was 620 mg/day, with 33.6% receiving doses in excess of 750 mg/day. Patients with nonwhite ethnicity, length of stay of at least 1 year, or history of prior state hospital admission were more likely to receive doses greater than 750 mg/day. Patients receiving quetiapine as antipsychotic monotherapy or in combination with other antipsychotics were equally likely to receive doses greater than 750 mg/day. Published anecdotal reports describe the use of quetiapine in excess of 800 mg/day and up to 2400 mg/day among patients not responding to lower doses, but currently there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy. CONCLUSIONS: Dosing of quetiapine in clinical practice is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of quetiapine in excess of 800 mg/day, double-blind randomized clinical trials are needed.

Antipsychotic Agents↗
PubMed2005

A cognitive, behaviorally based program for patients with persistent mental illness and a history of aggression, crime, or both: structure and correlates of completers of the program.

Standard psychiatric treatment programs have limited success in reducing recidivistic violent and criminal behavior in patients with persistent mental illness. A specialized, cognitive behavioral treatment program was developed for such a population. The purpose of this study was to identify factors that contribute to the patients' completing the program and to improve the selection criteria for program admission, so that those who participate are more likely to complete the program and be discharged. One hundred eighty-one patients with persistent mental illness with histories of aggression, crime, or both participated in a cognitive skills inpatient treatment program adapted for use with psychiatric patients. Ninety patients were able to complete the program and were discharged into the community. In comparison with the 91 who did not complete the program, those who did were less cognitively impaired and less impulsive. We present a new, intensive treatment program and define the predictors of successful completion of the program.

Adult↗
PubMed2004

An excitement subscale of the Positive and Negative Syndrome Scale.

BACKGROUND: We sought to develop and validate an excitement subscale from the Positive and Negative Syndrome Scale (PANSS) to allow the investigation of mania-like excitement symptoms in clinical trials of patients with schizophrenia using the PANSS and to provide clinicians with a short assessment tool for these states. METHODS: Baseline PANSS data from six double-blind, randomized registration trials of olanzapine, three in schizophrenia and three in acute bipolar mania, were used in these post-hoc analyses. Schizophrenia study data were pooled and randomly split in half. Exploratory principal component factor analysis was performed on half of the data. Factors were extracted based on minimum eigenvalue criteria (eigenvalue> or =1); loadings were determined using an equamax rotation. Confirmatory principal component factor analysis was performed on the other half of the data, retaining the original number of factors. Principal component factor analysis was also done for the pooled bipolar studies. Change in the new mania-like factor scores was then correlated with Young Mania Rating Scale (Y-MRS) scores in each bipolar study. RESULTS: Exploratory principal components analysis on the pooled schizophrenia data extracted five factors: negative, positive, excitement, cognitive, and depressive factors. The mania-like excitement factor was represented by four items (uncooperativeness, poor impulse control, excitement, and hostility), with only moderate loadings by tension and suspiciousness/persecution. Results were similar in the confirmatory analysis and the pooled bipolar studies. Change from baseline to endpoint for the mania-like factor correlated reasonably well (0.64-0.78) with change in Y-MRS scores in the bipolar studies. At baseline, bipolar patients scored higher than patients with schizophrenia on three of four PANSS mania-like factor items: poor impulse control, excitement, and hostility; the converse was true for most other PANSS items. CONCLUSION: Factor analyses of the PANSS consistently uncovered an excitement factor including uncooperativeness, poor impulse control, excitement, and hostility items. This factor may be useful in examining manic symptoms in studies where the addition of a scale specific to mania would be burdensome and where symptoms of excitement are part of the clinical presentation.

Adolescent↗
PubMed2004

COMT158 polymorphism and hostility.

The main study was designed primarily to compare the clinical effects of four antipsychotics in 157 patients with schizophrenia or schizoaffective disorder. The secondary genetic study, reported here, is based on a subset of 60 patients who consented to genotyping assays. Based on previous work with the catechol-O-methyltransferase (COMT) 158 polymorphism, we hypothesized that the Met-Met homozygotes would be more hostile than the heterozygotes and the Val-Val homozygotes. Hostility ratings at baseline were used to test this hypothesis. The Met-Met homozygotes (N = 7) were found to have significantly higher levels of hostility than the other patients (N = 53). The hypothesis was thus supported. The finding should be replicated in a larger sample.

Antipsychotic Agents↗
PubMed2004

The international suicide prevention trial (interSePT): rationale and design of a trial comparing the relative ability of clozapine and olanzapine to reduce suicidal behavior in schizophrenia and schizoaffective patients.

Suicidal behavior in patients with psychotic disorders represents a seriously undertreated life-threatening condition. The International Suicide Prevention Trial (InterSePT) is the first large-scale, prospective study designed to evaluate the potential of antipsychotic medications to reduce suicidal behaviors in patients with schizophrenia or schizoaffective disorder who are known to be at high risk for suicide. The unique challenges to study design and the solutions identified for the InterSePT study are described. These challenges included defining suicidal behavior in patients with psychosis, endpoint selection, determination of analytic strategy, and development of scales to assess suicidal behavior. Given the life-threatening nature of suicidal behavior, ethical considerations required that the design minimize suicide attempts and deaths. While the study focused primarily on treatment of suicide, opportunities were used to collect data in related areas of interest, including suicide risk factors, other efficacy measures (e.g., Positive and Negative Syndrome Scale, Covi Anxiety Scale, Calgary Depression Scale), adverse events, pharmacoeconomics, and pharmacogenetics. Because of the complexity of the design issues, a steering committee, suicide monitoring board, and publication committee were established to assist with their management.

Adolescent↗