William H. Meller

Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: a randomised, double-blind trial

BACKGROUND Several lines of evidence have led us to postulate that afferent vagal hyperactivity could be an important factor in the pathophysiology of the eating disorder bulimia nervosa. Ondansetron is a peripherally active antagonist of the serotonin receptor 5-HT3, and is marketed for prevention of vagally-mediated emesis caused by cancer chemotherapeutic agents. We investigated the effects of ondansetron on bulimic behaviours in patients with severe and chronic bulimia nervosa in a randomised, double-blind, placebo-controlled study. METHODS We enrolled patients with severe bulimia nervosa (at least seven coupled binge/vomit episodes per week). The patients were otherwise healthy, their weight was normal, and they were not receiving medical or psychiatric treatment. During the first week of the study, patients recorded all eating-behaviour events to establish a baseline. In the second week, all patients received placebo, but were told that they were receiving either placebo or active drug. At the end of this single-blind phase, patients were randomly assigned placebo or ondansetron (24 mg daily) for a further 4 weeks. The primary outcome measure was the number of binge/vomit episodes per week. Data were analysed by intention to treat. FINDINGS 29 patients met the inclusion criteria, of whom 28 completed the baseline study, and 26 completed the single-blind placebo week. 12 patients were assigned placebo, and 14 ondansetron; one patient in the ondansetron group dropped out owing to accidental injury. During the 4th week of double-blind treatment, mean binge/vomit frequencies were 13.2 per week (SD 11.6) in the placebo group, versus 6.5 per week (3.9) in the ondansetron group (estimated difference 6.8 [95% CI 4.0-9.5]; p<0.0001). The ondansetron group also showed significant improvement, compared with the placebo group, in two secondary indicators of disease severity. The amount of time spent engaging in bulimic behaviours was decreased on average by 7.6 h per week in the ondansetron group, compared with 2.3 h in the placebo group (estimated difference 5.1 [0.6-9.7]). Similarly, the number of normal meals and snacks increased on average by 4.3 normal eating episodes without vomiting per week in the ondansetron group, compared with 0.2 in the placebo group (estimated difference 4.1 [1.0-7.2]). INTERPRETATION The decrease in binge-eating and vomiting under ondansetron treatment was not achieved by compensatory changes in eating behaviour such as by a smaller number of binges of longer duration, or by not eating, or by binge-eating without vomiting. Instead, our findings indicate a normalisation of the physiological mechanism(s) controlling meal termination and satiation. Since meal termination and satiety are mainly vagally mediated functions, since binge-eating and vomiting produce intense stimulation of vagal afferent fibres, and since ondansetron and other 5-HT3 antagonists decrease afferent vagal activity, the symptom improvement may result from a pharmacological correction of abnormal vagal neurotransmission.

General Medical and Pharmacy Claims Expenditures in Users of Behavioral Health Services

OBJECTIVE: To quantify the magnitude of general medical and/or pharmacy claims expenditures for individuals who use behavioral health services and to assess future claims when behavioral service use persists.DESIGN: Retrospective cost trends and 24-month cohort analyses.SETTING: A Midwest health plan.PARTICIPANTS: Over 250,000 health plan enrollees during 2000 and 2001.MEASUREMENTS: Claims expenditures for behavioral health services, general medical services, and prescription medications.MAIN RESULTS: Just over one tenth of enrollees (10.7%) in 2001 had at least 1 behavioral health claim and accounted for 21.4% of total general medical, behavioral health, and pharmacy claims expenditures. Costs for enrollees who used behavioral health services were double that for enrollees who did not use such services. Almost 80% of health care costs were for general medical services and medications, two thirds of which were not psychotropics. Total claims expenditures in enrollees with claims for both substance use and mental disorders in 2000 were 4 times that of those with general medical and/or pharmacy claims only. These expenditures returned to within 15% of nonbehavioral health service user levels in 2001 when clinical need for behavioral health services was no longer required but increased by another 37% between 2000 and 2001 when both chemical dependence and mental health service needs persisted.CONCLUSIONS: The majority of total claims expenditures in patients who utilize behavioral health services are for medical, not behavioral, health benefits. Continued service use is associated with persistently elevated total general medical and pharmacy care costs. These findings call for studies that better delineate: 1) the interaction of general medical, pharmacy, and behavioral health service use and 2) clinical and/or administrative approaches that reverse the high use of general medical resources in behavioral health patients.

What is integrated care

Abstract Increasing awareness of mental illnesss impact on medical and psychiatric health has accelerated global efforts to integrate medical and behavioural health services. As the field of integration has advanced, numerous integrated programmes have been implemented. In examining the impact of these programmes, it is important to maintain a standardized vocabulary to describe the various components of their integration. Additionally important is examination of how these programmes impact elements of patient care and the healthcare system. Specifically, what value do they bring? This article will discuss the importance of carefully assessing the value integrated services bring to patients, and questioning whether they do so in ways in which todays segregated world of medical and behavioural health cannot. This article will also explore the various settings in which medical and behavioural integration can bring added value.

Effect of ondansetron, a 5-HT3 receptor antagonist, on the dynamic association between bulimic behaviors and pain thresholds.

Abstract Thresholds for detection of both pressure and thermal pain are elevated in patients with bulimia nervosa. The present study was aimed at determining (1) if pressure pain detection thresholds (PDT) varied dynamically with the primary disease symptoms of binge eating and vomiting and (2) if the elevation in PDT was effected by treatment with ondansetron (ONDAN), a 5‐HT3 receptor antagonist. PDT was defined as the mean of the minimal amount of pressure (measured in g) perceived as painful when exerted by a 1 mm2 blunted point onto the center of the ventral surface of the ungual phalanx of digits 2‐5 of the non‐dominant hand. Fourteen female patients with severe bulimia nervosa (currently >seven binge/vomit episodes per week;>2 years illness duration) served as participants. PDT were evaluated at weekly intervals during the course of ongoing treatment studies (double‐blind and ‘open’ label) investigating the therapeutic effects of ONDAN. Data were analyzed by random regression analyses, allowing for the repeated‐measures and non‐orthogonal design. Data collected from 14 patients under the no‐drug condition indicated that PDT increased over the interval between binge/vomit episodes, with significant elevations occurring at times when patients had naturally exceeded their average inter‐binge interval. Eleven of these 14 patients underwent 4 weeks of ONDAN treatment. Under this drug condition, the time since the last binge/vomit episode was no longer a significant predictor of PDT. These patients also experienced a significant reduction in the frequency of bulimic behaviors, a finding reported in detail elsewhere. The above finding from untreated patients support the involvement of a common underlying mechanism driving both the increase in pain detection thresholds and the occurrence of the next bulimic episode. This possibility is further supported by the findings that ONDAN treatment is associated with a significant moderation of both variables. The effect of ONDAN may be mediated by blockade of afferent vagal neurotransmission, although other mechanisms must be considered.

Hypothalamic pituitary gonadal axis dysregulation in depressed women.

In order to examine HPG axis regulation in women with major depression, luteinizing hormone (LH) pulsativity was studied in 26 depressed and 24 normal women. Blood was sampled every 10 min for an 8-h period during the first week of their menstrual cycle. LH pulsatile release was analyzed using the computerized cluster analysis algorithm of Veldhuis and Johnson and spectral analysis. Compared to control women, depressed women had slower frequency dysrhythmic LH pulsatility. These results are consistent with a previously published pilot study which reported results of the first 23 subjects [Am. J. Psychiat. 154 (1997) 1454].

Blunted acth response to hypoglycemic stress in depressed patients but not in patients with schizophrenia

In this study, 7 hospitalized patients with major depression (MD), 5 hospitalized patients with schizophrenia (S), and 13 control subjects (C) were administered 0.15 units/kg of regular insulin at 1600 h by intravenous bolus infusion. ACTH, cortisol, and glucose levels were measured intermittently for 2h following infusion. Baseline ACTH, cortisol and glucose levels were similar in Cs, MDs, and Ss. The mean glucose nadir was equivalent for Cs, patients with MD, and patients with S. Patients with MD had a blunted ACTH response (F = 3.28; df = 12,126; p = .0004) and cortisol response (F = 4.20; df = 12,132; p = .0001) to hypoglycemia when compared to Cs and patients with S. Carroll Depression Rating Scale scores in patients with S (23 +/- 10) were similar to patients with MD (30 +/- 8) and significantly higher than in controls (1 +/- 2) (F = 55.2; df = 2.22; p = .0001). These findings suggest that patients with MD show different ACTH and cortisol responses to hypoglycemic stress which are not explained by negative feedback of baseline ACTH or cortisol, glucose nadir, or the number of depressive symptoms per se.

Misdiagnosed Delirium in Patient Referrals to a University-Based Hospital Psychiatry Department

The authors examined the factors associated with referral errors in which the presence of delirium was ostensibly not recognized by medical staff personnel. Medical records of 541 university-hospital patients consecutively referred for psychiatric consultation were scrutinized for extant delirium. The data indicated that a greater likelihood of a missed diagnosis was associated with younger age; referrals outside of family practice service; orientation as to person, place, and time; and a history of bipolar affective disorder or psychosis. The ramifications of failure to diagnose existing delirium include increased morbidity and mortality, longer length of hospital stay, and increased healthcare costs.

Comorbidity of major depression and conduct disorder

The association of depression and conduct disorder is common and often perplexing in child psychiatry. Using a systematic retrospective chart review, various symptom, demographic and family history variables were compared between depression with comorbid conduct disorder and depression alone. Variables which differed between groups were entered into a stepwise discriminative function analysis. The four variables which discriminated between groups were anxiety, witness to family violence, illegal behavior, and impulsive behavior. The strongest discriminating variable, anxiety, was associated with depression without comorbid conduct disorder. These results emphasize the heterogeneity of childhood depression and potential importance of anxiety.

Changes in psychiatric consultations over ten years

We report on the day-to-day functions of a consultation-liaison psychiatric service during a two-month period separated by ten years. As general hospitals transformed their delivery of services during the 1990s, we hypothesized that the day-to-day role of the consultation-liaison service would change in terms of the population served, timing of evaluations, and recommended interventions. Using a chart review, we retrospectively examined consultations referred to an adult consultation-liaison service at a university hospital during the same two-months in 1990 (N=75) and 2000 (N=90). Patients in 2000 were less educated, more likely to be divorced and more likely to be minorities. The 2000 patients appeared to have more severe psychiatric illness and to be more medically complicated. These findings have implications in the context of cost effective health care.

Stimulation of the pituitary-adrenal axis with arginine vasopressin in patients with depression.

The ACTH response to arginine vasopressin was the same in patients with depression while cortisol response was significantly greater in patients with depression when compared to the control population. These findings are consistent with the hypothesis that vasopressin corticotroph receptors are not downregulated in depression and that there is increased adrenal responsiveness in patients with depression to endogenous ACTH.