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Biomedical subjects

Peter F Buckley

Publications and source records attributed to Peter F Buckley.

28 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

Aripiprazole: efficacy and tolerability profile of a novel-acting atypical antipsychotic.

Aripiprazole, the latest atypical antipsychotic to come to clinical practice, has a proposed mechanism of action different to other agents, most notably in its partial agonist action at dopamine (D2) receptors and at serotonin (5HT1A) receptors. Placebo-controlled comparative trials of aripiprazole confirm efficacy for positive, negative and general psychopathology. Treatment-emergent adverse effects appear low. Aripiprazole is associated with low propensity for extrapyramidal side effects, an absence hyperprolactinemia and a low propensity for weight gain. Aripiprazole's clinical role will be determined by clinical experience, additional phase IV studies, and comparative information for this agent with respect to the efficacy and tolerability profiles of other atypical antipsychotic medications.

Antipsychotic Agents↗

Head size and schizophrenia.

There is a small but intriguing body of literature which suggests that head size may be reduced in patients with schizophrenia. This literature sits alongside more substantial and compelling evidence that there is a reduction in cerebral volume in schizophrenia. As an extension of earlier work, measures of extracranial head size derived from standard anthropometric approaches were assessed in 44 patients and 46 control subjects. Head size was found to be normal in schizophrenia. The relationship of brain size to head size is elaborated.

Adult↗

Medication management in patients with chronic non-malignant pain. A review of the use of a drug withdrawal protocol.

One hundred and twenty-four (71%) of 173 patients, admitted consecutively to the Inpatient Service of the University of Washington Multidisciplinary Pain Center, were consuming narcotic/sedative drugs and 49 (29%) were not. We describe the use of a drug withdrawal protocol entailing outpatient drug consumption diaries; a 48 h inpatient drug profile; the use of drug equivalence tables to convert drugs consumed to a methadone/phenobarbital pain cocktail and the subsequent tapering of the active contents of the pain cocktail. Diaries reliably revealed the types of drug consumed but not extent of consumption. Narcotic consumption in particular tends to be underreported. For patients with a history of a drug problem and those who consume narcotics heavily during the first day of profile, a 48 h profile is appropriate. In others a 24 h profile is safe. Objective signs of excessive consumption or a withdrawal syndrome were noted in 2 patients during the profile period and in 4 patients during the taper from pain cocktail. Published tables appear to give a reasonable estimate of drug equivalence. The importance of monitoring patients during the protocol is emphasized.

Analgesics, Opioid↗

Reflections on leadership as chair of a department of psychiatry.

The chair of a department of psychiatry has a complex role, balancing leadership of the department with the broader role as an institutional leader. The competencies and training opportunities for this role are ill-defined. Mentorship, strong administrative supports, and champions for psychiatry within the academic health center are key resources for the chair. The continued need to be a knowledgeable leader in the national trends of education, research, and clinical systems of care is a real challenge.

Academic Medical Centers↗