Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume.

Lithium and quetiapine are effective treatments for bipolar disorder, but their potential neuroprotective effects in humans remain unclear. A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients (n=26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control sample was also collected (n=20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6 mmol l-1, n=20) or quetiapine (flexibly dosed up to 800 mg per day, n=19) monotherapy. At baseline, compared with healthy control subjects, patients with FEM showed reduced grey matter in the orbitofrontal cortex, anterior cingulate, inferior frontal gyrus and cerebellum. In addition, patients had reduced internal capsule white matter volume bilaterally (t1,66>3.20, P<0.01). Longitudinally, there was a significant treatment × time effect only in the white matter of the left internal capsule (F2,112=8.54, P<0.01). Post hoc testing showed that, compared with baseline, lithium was more effective than quetiapine in slowing the progression of white matter volume reduction after 12 months (t1,24=3.76, P<0.01). Our data support the role of lithium but not quetiapine therapy in limiting white matter reduction early in the illness course after FEM.

A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study.

BACKGROUND: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. METHODS: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. RESULTS: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. CONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial.

BACKGROUND: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. METHODS: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. RESULTS: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. CONCLUSIONS: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

Conscious sedation of pediatric dental patients: an investigation of chloral hydrate, hydroxyzine pamoate, and meperidine vs. chloral hydrate and hydroxyzine pamoate.

This study evaluated two oral sedative regimens for the conscious sedation of pediatric dental patients (mean age 37.0 months) unmanageable by traditional behavior management techniques. Regimen A included chloral hydrate (Noctec--E.R. Squibb and Sons, Princeton, NJ) at 50 mg/kg with 25 mg hydroxyzine pamoate (Vistaril--Pfizer Laboratories, New York, NY), plus meperidine (Demerol--Winthrop-Breon, New York, NY) at 1.5 mg/kg. Regimen B included chloral hydrate at 50 mg/kg with 25 mg hydroxyzine pamoate. In a crossover research design, 10 patients were assigned randomly to receive one regimen, to be followed by the alternative regimen during the second appointment. The primary purpose of this study was to determine if meperidine would improve patient behavior, and increase the prevalence of respiratory compromise. A secondary purpose of the study was to develop an objective method to assess behavior during the conscious sedation of pediatric dental patients. Results revealed that the addition of oral meperidine to chloral hydrate and hydroxyzine pamoate resulted in improved behavior (P less than 0.01) during local anesthetic injection, rubber dam delivery, and the operative dental procedure. There was no increase in the prevalence of respiratory compromise with the addition of meperidine.

Early detection is the key to successful treatment.

In the United States today, healthcare reform is prompting an increase in education, community awareness, and early detection, as well as a decrease in healthcare costs and days missed at work due to illness. A program like the HVE Program accomplishes all of these things. People are starting to take a more active role in their healthcare. The advantages and benefits of preventive and alternative medicine are now recognized as a way to lower the cost of healthcare and as a way to minimize the loss of human life via early detection and treatment of disease. Continuous improvement, support from hospital administration, dedication of staff members, and community participation have enabled the Heart and Vascular Evaluation Program to evolve into the valuable service it is today--and the kind of service that will lead us into the future of healthcare.

Physicians' perceptions about managed care restrictions on antibiotic prescribing.

The purpose of this study was to compare physicians' perceptions about managed care restrictions on drug prescribing with objective measures of the restrictions' effects. When asked a general question, 17 emergency medicine physicians in one urban, university hospital answered that they had to prescribe an antibiotic that was not their first choice because of managed care restrictions 32% of the time. The actual frequency of prescribing other than first-choice antibiotics, which was determined by asking the same physicians about the prescription of specific antibiotics for specific patients seen recently in the emergency department, was 6% ( p <.0001). We conclude that emergency medicine physicians treating patients in one managed care system significantly overestimated the restrictions imposed by managed care formularies on their antibiotic prescribing practices. Additional studies are warranted to measure the extent of this bias.