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Biomedical subjects

Peter F Buckley

Publications and source records attributed to Peter F Buckley.

At least 19 recordsLinked to original sources
PubMed2005

Clinicians' recognition of the metabolic adverse effects of antipsychotic medications.

There is a growing concern regarding the propensity of second generation antipsychotics (SGAs) to induce weight gain and metabolic adverse effects. Recent consensus guidelines have recommended assessment and monitoring procedures to appropriately detect and manage these adverse effects. This study addresses the appreciation and readiness of clinicians to implement management guidelines for these adverse effects. Respondents indicated awareness of the risks of treatment with SGAs. The extent of monitoring for metabolic adverse effects was low and inconsistent across measures and in frequency of evaluation. Ongoing efforts are needed to support and encourage change in clinician practice.

Antipsychotic Agents↗
PubMed2005

Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism.

Weight gain has been documented as a significant adverse effect associated with many of the atypical antipsychotic medications. Several recent reports have linked a -759C/T polymorphism of the 5HT2C receptor gene and obesity as well as chlorpromazine, risperidone, and clozapine induced to weight gain. This aim was to determine the association between changes in body mass index (BMI) during clozapine treatment and the -759C/T polymorphism of the 5HT2C receptor gene. This study included 41 patients with treatment-refractory schizophrenia (DSM-IV) who were followed prospectively during treatment with clozapine. Weight and height measurements were obtained prior to starting clozapine and after 6-months of treatment. Genomic DNA was isolated from a whole blood sample and analyzed for the -759C/T polymorphism of the 5HT2C receptor gene. A chi(2) analysis comparing whether or not the subjects carried a -759T allele in subjects grouped as having an increase of more or less than 7% of their baseline BMI during treatment with clozapine found that the presence of the -759T allele was significantly higher in subjects with less than or equal to a 7% increase in baseline BMI compared to those with a greater than 7% increase in BMI. A multiple linear regression analysis showed that both baseline BMI and the presence or absence of the -759T allele had significant effects on 6-month BMI. The T allele may have a protective function in preventing significant weight gain from clozapine. Subjects without the -759T variant allele were at a greater risk for weight gain from clozapine over 6-months compared to those with the -759T allele.

Adult↗
PubMed2005

Stimulus sequence affects schizophrenia-normal differences in event processing during an auditory oddball task.

Schizophrenia patients have difficulty distinguishing relevant from irrelevant auditory information. Auditory oddball paradigms are commonly used to investigate the processing of stimulus relevance. The present study used dense-array EEG and distributed source reconstructions to examine schizophrenia-normal differences in the processing of targets and standards as a function of the temporal sequence of stimuli. Brain responses were evaluated separately for early and late standards (standards 1-3 and 4-6 following a target, respectively) and early and late targets (those following 2-3 standards and 4-6 standards, respectively). The latencies of peaks (N1, P2, P3) in the event-related potential (ERP) waveforms did not differ between schizophrenia and normal subjects. However, schizophrenia-normal differences in neural activity, derived from minimum norm estimation, occurred at specific times during stimulus processing as a function of stimulus sequence. Schizophrenia patients displayed smaller activity than normals in early ERPs (left hemispheric N1, right frontal P2) to late targets, and they produced P3-like responses to late standards. Furthermore, during the P2/N2 time interval, opposite patterns of brain activity were elicited in schizophrenia and normal subjects in response to standards, indicating different neural responses to the same stimulus events. These results suggest attention allocation to task-irrelevant stimuli in schizophrenia, consequent upon insufficient representation of stimulus significance and context. Thus, schizophrenia compromises the ability to properly use context to solve even simple cognitive problems.

Acoustic Stimulation↗
PubMed2005

Optimizing treatment of schizophrenia. Enhancing affective/cognitive and depressive functioning.

Recognition and treatment of schizophrenia has largely focused on positive symptoms of the disorder, such as delusions, hallucinations, and disorganization. However, other important symptoms, such as depression, cognition, and social functioning, have not received comparable attention. Fifty percent of schizophrenic patients suffer from comorbid depression, which is a major risk factor for suicide in this population, while 10% to 25% suffer from comorbid obsessive-compulsive disorder. Cognitive deficits commonly observed in patients with schizophrenia include problems with concentration, attention, and memory, as well as problem-solving and verbal skills. These deficits are observed at early stages of the illness and can predict deficits in functional capabilities, such as occupational and social skills, educational attainment, and the ability to live independently. The severity of such impairments affects all patient in this population, including up to 10% of patients working full time and up to one third of those working part time. In light of the debilitating effects of depression, cognitive impairment, and other aspects of affective functioning on the quality of life of patients with schizophrenia, physicians need to partner with their patients to address these concerns and determine an appropriate treatment regimen. This can be done with simple functional-based cognitive questioning, the use of evidence-based psychosocial practices, and psychoeducation on the many pharmacotherapeutic options. It is recommended that depressive or suicidal symptoms of schizophrenia be treated with an antidepressant or mood stabilizer only if the symptoms have not subsided after treatment of the psychosis with an atypical antipsychotic. Additionally, relative to older medications, atypicals have demonstrated benefit in improving some of the cognitive impairments.

Affective Symptoms↗
PubMed2005

A three-dimensional morphometric study of craniofacial shape in schizophrenia.

BACKGROUND: Subtle dysmorphogenesis of the craniofacial region constitutes important corroborating evidence of the neurodevelopmental origins of schizophrenia. Advances in facial visualization now allow for three-dimensional anthropometric evaluations of potentially greater discriminatory power in examining the complex geometric relationships of facial topography. METHOD: Sixty-five anthropometrically derived landmarks were identified from three-dimensional facial images collected from 14 patients with schizophrenia and 11 comparison subjects, imaged with a high-resolution, portable laser scanner. RESULTS: Using the Procrustes morphometric approach for shape analysis, the difference in mean shapes was highly significant, with patients exhibiting superoinferior elongation of the face. CONCLUSIONS: The topography of craniofacial anomalies in schizophrenia is not random and points to midline deformation.

Adult↗
PubMed2005

Second-generation antipsychotic medications in the treatment of mood disorders: focus on aripiprazole.

Second-generation antipsychotic medications offer a broader range of therapeutic efficacies than first-generation agents. Consequently, our field has witnessed a rapid expansion of the use of second-generation antipsychotic drugs for several conditions beyond psychosis. The use of second-generation antipsychotic medications has been most pronounced in mood disorders, especially in bipolar disorders. Information about the agents clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole in terms of their efficacy and tolerability in bipolar disorder is now available. Aripiprazole, a new agent whose proposed mechanism(s) of action differs from that of other agents, has been shown in placebo-controlled comparative trials in bipolar patients to be an effective and well tolerated treatment option for this patient group. The role of second-generation antipsychotic medications in the therapeutic armamentarium for bipolar disorders will be determined by clinical experience, by additional phase IV studies and by trials that compare second-generation antipsychotics with each other and also with mood-stabilizing medications. There is also a pressing need for additional information on the long-term efficacy and safety of each second-generation antipsychotic agent during maintenance therapy for bipolar disorders.

Antipsychotic Agents↗
PubMed2005

Olanzapine: a critical review of recent literature.

The purpose of this review is to critically review the current literature on olanzapine with an emphasis on emergent themes and key findings in the use of this agent for the treatment of mood disorders and schizophrenia. New information continues to emerge on the impact of olanzapine on schizophrenia and on aspects of the course of mood disorders. There are also continued efforts to understand, predict and manage the side-effect risk with olanzapine.

Antipsychotic Agents↗
PubMed2004

Rate of stimulation affects schizophrenia-normal differences on the N1 auditory-evoked potential.

The present study examined how increasing the rate of steady-state stimulation affects schizophrenia-normal differences on the N1 auditory-evoked potential, an index of auditory integration. Dense-array EEG was recorded while schizophrenia and normal subjects heard 1 kHz tones amplitude modulated at 10, 20, 40, or 80 Hz. Spectral power across frequency and time was calculated. The typically lower N1 amplitude in schizophrenia, observed at the 10 Hz burst rate, increased to nearly equal that of normal individuals at 20 Hz. Unlike normal subjects, schizophrenia subjects' power at N1 failed to increase at the 40 and 80 Hz burst rates. These results suggest steady-state stimuli, up to a point, provide the extra information needed for schizophrenia patients to more efficiently integrate auditory information.

Acoustic Stimulation↗
PubMed2004

Efficacy and tolerability of quetiapine in poorly responsive, chronic schizophrenia.

With the notable exception of clozapine, there is at present insufficient information on the efficacy of atypical antipsychotic medications in patients with poorly responsive schizophrenia. The present study reports on the efficacy and tolerability of quetiapine and haloperidol in patients with schizophrenia who showed no response to treatment with fluphenazine. This study is a post hoc subanalysis of an 8-week, double-blind study of patients receiving quetiapine 600 mg/day or haloperidol 20 mg/day. The proportion of patients classified as "Clinical Global Impression responders" (defined as Clinical Global Impression Severity of Illness score of < or = 3 at study end) was greater in the quetiapine group compared with the haloperidol group (51% vs. 25%; P = 0.023). Overall, quetiapine was well tolerated with less extrapyramidal side-effects and reduction in prolactin when compared to haloperidol. Weight gain was modest but more apparent in quetiapine-treated patients. Quetiapine is an appropriate treatment choice in patients who do not respond to prior antipsychotic treatment.

Adult↗
PubMed2004

Maintenance treatment for schizophrenia with quetiapine.

With the majority of current information being derived from short-term clinical trials, the impact of atypical antipsychotics during maintenance treatment of schizophrenia is of considerable interest, although only limited data are available at present. The present report is an analysis of data that are available up to 156 weeks after the start of an open-label extension (OLE) phase of three, double-blind randomized trials in quetiapine-treated patients who responded to an initial 6-week treatment period. The mean daily quetiapine dose (range 150-750 mg) was 439.5 mg for patients included in the brief psychiatric rating scale (BPRS) and 438.5 mg for patients included in the clinical global impression (CGI) analyses. The initial mean acute phase BPRS total score (40.67; n=258) and CGI severity of illness score (4.81; n=259) were reduced at the start of the OLE to 13.94 and 3.00, respectively. After 156 weeks, endpoint scores were 9.04 for BPRS and 2.43 for CGI severity of illness. Although limited by patient attrition, these OLE data suggest that an initial beneficial response with quetiapine treatment can be maintained over a long-term period.

Brief Psychiatric Rating Scale↗
PubMed2004

Effective dosing and dose equivalency of second-generation antipsychotic medications.

Dosing patterns with second-generation antipsychotic medications (SGAs) are dynamic, with some SGAs surpassing current recommendations while others are declining in dose since their initial regulatory guidelines. Pertinent recent studies and available pharmacoepidemiologic reports, information, and expert consenses are reviewed herein to illuminate current thinking on the topic of dosing with SGAs. There is a need for fixed-dose studies of each SGA. Additionally, dosing should be a primary consideration when designing and subsequently interpreting comparative studies between SGAs.

Antipsychotic Agents↗
PubMed2004

Insight and its relationship to violent behavior in patients with schizophrenia.

OBJECTIVE: Lack of insight affects the management of schizophrenia. The interrelationship between lack of insight and illness attributes in patients with schizophrenia who commit violent acts is important and underresearched. METHOD: One hundred fifteen violent patients with schizophrenia in a jail or court psychiatric clinic were evaluated on measures of symptoms, illness severity, insight into illness, and the legal consequences of their illness ("forensic insight"). A sample of nonviolent patients served as a comparison group. RESULTS: Compared with the nonviolent cohort, violent patients were more symptomatic, had poorer functioning, and had a more prominent lack of insight. Deficits of insight into illness coexisted with a lack of forensic insight, which was also associated with psychosis. CONCLUSIONS: Patients with schizophrenia who commit violent acts have insight deficits, including lack of awareness of the legal implications of their behavior. Targeted interventions to improve insight and treatment compliance in this population are warranted.

Adult↗
PubMed2004

Efficacy of quetiapine for the treatment of schizophrenia: a combined analysis of three placebo-controlled trials.

OBJECTIVE: To determine the effectiveness of quetiapine (Seroquel) against specific aspects of schizophrenic symptomatology. RESEARCH DESIGN AND METHODS: Combined data from three placebo-controlled, double-blind, randomised trials that had previously demonstrated quetiapine's overall clinical effectiveness and tolerability were analysed. Efficacy assessments evaluated were the Clinical Global Impression (CGI) Severity of Illness score, Brief Psychiatric Rating Scale (BPRS) factors I-V, BPRS positive symptom cluster score and 18 individual BPRS items. The Simpson-Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), changes in weight and prolactin concentrations and the recording of adverse events comprised the main tolerability measures. RESULTS: Efficacy assessments were available for a total of 426 quetiapine patients (mean age 36.9 years) with a DSM-IIIR diagnosis of schizophrenia; 502 patients were included in the tolerability analyses. The mean quetiapine dose was 300.5 mg/day with a mean maximum dose of 686.0 mg/day. Quetiapine was efficacious across a broad range of symptoms, including depression, anxiety and hostility. Significant improvements compared with placebo were noted for CGI Severity of Illness (p < 0.001) and in 14 of the 18 individual BPRS items (p < 0.001). Positive symptoms also improved (p < 0.01 at Week 2 and p < 0.001 from Week 3); greater improvements were observed in patients who received at least 400 mg/day quetiapine. Quetiapine was generally well tolerated: 4.0% of patients withdrew from treatment due to adverse events compared with 3.0% of placebo patients. Akathisia occurred in 2.0% and 2.5% of quetiapine and placebo patients, respectively. Similar decreases in prolactin levels for quetiapine (-10.0 microg/L) and placebo (-10.9 microg/L) were noted from baseline to end of treatment. Agitation and headache, the most common adverse events, were comparable in the quetiapine and placebo groups (agitation: 19.3% vs. 20.3%, respectively; headache: 19.1% vs. 17.3%, respectively). CONCLUSIONS: The results of this combined analysis confirm the individual findings of the three pivotal studies to demonstrate that quetiapine is effective across several domains of schizophrenia, improving positive, negative and depressive symptoms and reducing agitation, aggression and hostility. Similarly, the analysis reiterated the good tolerability profile of quetiapine, particularly in terms of its placebo-like effects on prolactin levels and incidence of extrapyramidal symptoms (EPS).

Adolescent↗
PubMed2004

Dose response and atypical antipsychotics in schizophrenia.

Based on information from clinical trials, both the efficacy and adverse effects of conventional antipsychotics in the treatment of schizophrenia are dose related. The overlapping nature of these dose-response profiles limits the use of these agents. Atypical antipsychotics provide greater relief across the comorbid symptom domains of schizophrenia, but dose-response studies and clinical experience have revealed that some of these drugs also have dose limitations. This article reviews the dose-response relationships of the atypical antipsychotics as presented predominantly in pivotal, randomised studies (double-blind and otherwise). Limited data indicate that clozapine shows dose-related efficacy up to 600 mg/day in patients with treatment-resistant schizophrenia. However, higher dosages of clozapine may be associated with the risk of seizures. Risperidone demonstrates dose-related adverse events that compromise efficacy. The dose-response relationships for ziprasidone, quetiapine and aripiprazole are less well established. The efficacy of olanzapine appears to be dose related within the recommended dosage range of 10-20 mg/day, but clinical trials that have explored higher dosages suggest improved efficacy. Furthermore, the higher doses are not associated with a significantly increased incidence of adverse events. Further studies are clearly needed to fully characterise the dose-response relationships of atypical antipsychotics.

Antipsychotic Agents↗
PubMed2004

Naturalistic studies of second generation antipsychotics in the treatment of schizophrenia.

Undoubtedly, the pharmacological treatment of schizophrenia has changed dramatically over the last 10 years. Large, double-blind, placebo-controlled trials have ushered the availability of each new antipsychotic. However, there has been an information lag because of the relative paucity of long term, comparative studies among second-generation antipsychotics. While we await such evidence, naturalistic studies have helped to provide useful information on the pattern of use, patient response, and tolerability of these new agents in clinical practice. This review provides an account of representative studies for each second generation antipsychotic, which illustrate the contributions of naturalistic studies to our understanding of the evolving pharmacotherapy of schizophrenia.

Antipsychotic Agents↗
PubMed2004

The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update.

BACKGROUND: The Texas Medication Algorithm Project (TMAP) has been a public-academic collaboration in which guidelines for medication treatment of schizophrenia, bipolar disorder, and major depressive disorder were used in selected public outpatient clinics in Texas. Subsequently, these algorithms were implemented throughout Texas and are being used in other states. Guidelines require updating when significant new evidence emerges; the antipsychotic algorithm for schizophrenia was last updated in 1999. This article reports the recommendations developed in 2002 and 2003 by a group of experts, clinicians, and administrators. METHOD: A conference in January 2002 began the update process. Before the conference, experts in the pharmacologic treatment of schizophrenia, clinicians, and administrators reviewed literature topics and prepared presentations. Topics included ziprasidone's inclusion in the algorithm, the number of antipsychotics tried before clozapine, and the role of first generation antipsychotics. Data were rated according to Agency for Healthcare Research and Quality criteria. After discussing the presentations, conference attendees arrived at consensus recommendations. Consideration of aripiprazole's inclusion was subsequently handled by electronic communications. RESULTS: The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations. CONCLUSION: Consensus on algorithm revisions was achieved, but only further well-controlled research will answer many key questions about sequence and type of medication treatments of schizophrenia.

Algorithms↗
PubMed2003

Treatment of the psychotic patient who is violent.

Aggression among patients with serious mental illness occurs relatively infrequently, but it is a significant concern for patients, relatives, mental health professionals, and the public. Recognition of this risk and providing access and continuity of appropriate psychiatric care should be major clinical and administrative objectives in the management of violence in psychotic patients. To date, pharmacologic approaches have been unclear and inconsistent. At present, typical antipsychotics continue to have a primary role in acute management and in long-term management, in which noncompliance necessitates the use of long-acting depot neuroleptic preparations. Atypical antipsychotics in acute and long-acting intramuscular forms doubtless will influence and expand the choice for acute management of hostile psychotic patients and the long-term management of poorly compliant patients who are at risk to become violent on relapse. Persistent aggression should be managed by atypical antipsychotics with a preferential indication for clozapine, for which the most data on efficacy are available. The role of adjunctive medications is presently unclear. A major focus of care should be to refine legal processes and to conduct intervention studies aimed at enhancing treatment compliance. Violence risk reduction is not only crucial from a societal perspective, but also it is a humanitarian necessity to alleviate the burden and stigma for patients with serious mental illness.

Antipsychotic Agents↗