Olanzapine versus placebo for out-patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric illness associated with significant morbidity and mortality. There is little empirical support for specific treatments and new approaches are sorely needed. This two-site study aimed to determine whether olanzapine is superior to placebo in increasing body mass index (BMI) and improving psychological symptoms in out-patients with AN. METHOD: A total of 23 individuals with AN were randomly assigned in double-blind fashion to receive olanzapine or placebo for 8 weeks together with medication management sessions that emphasized compliance. Weight, other physical assessments and measures of psychopathology were collected. RESULTS: End-of-treatment BMI, with initial BMI as a covariate, was significantly greater in the group receiving olanzapine [F(1, 20)=6.64, p=0.018]. Psychological symptoms improved in both groups, but there were no statistically significant group differences. Of the 23 participants, 17 (74%) completed the 8-week trial. Participants tolerated the medication well with sedation being the only frequent side effect and no adverse metabolic effects were noted. CONCLUSIONS: This small study suggests that olanzapine is generally well tolerated by, and may provide more benefit than placebo for out-patients with AN. Further study is indicated to determine whether olanzapine may affect psychological symptoms in addition to BMI.

Early response to antidepressant treatment in bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) is a serious psychiatric disorder characterized by frequent episodes of binge eating and inappropriate compensatory behavior. Numerous trials have found that antidepressant medications are efficacious for the treatment of BN. Early response to antidepressant treatment, in the first few weeks after medication is initiated, may provide clinically useful information about an individual's likelihood of ultimately benefitting or not responding to such treatment. The purpose of this study was to examine the relationship between initial and later response to fluoxetine, the only antidepressant medication approved by the US Food and Drug Administration (FDA) for the treatment of BN, with the goal of developing guidelines to aid clinicians in deciding when to alter the course of treatment. METHOD: Data from the two largest medication trials conducted in BN (n=785) were used. Receiver operating characteristic (ROC) curves were constructed to assess whether symptom change during the first several weeks of treatment was associated with eventual non-response to fluoxetine at the end of the trial. RESULTS: Eventual non-responders to fluoxetine could be reliably identified by the third week of treatment. CONCLUSIONS: Patients with BN who fail to report a 60% decrease in the frequency of binge eating or vomiting at week 3 are unlikely to respond to fluoxetine. As no reliable relationships between pretreatment characteristics and eventual response to pharmacotherapy have been identified for BN, early response is one of the only available indicators to guide clinical management.

The slippery slope: prediction of successful weight maintenance in anorexia nervosa.

BACKGROUND: Previous research has found that many patients with anorexia nervosa (AN) are unable to maintain normal weight after weight restoration. The objective of this study was to identify variables that predicted successful weight maintenance among weight-restored AN patients. METHOD: Ninety-three patients with AN treated at two sites (Toronto and New York) through in-patient or partial hospitalization achieved a minimally normal weight and were then randomly assigned to receive fluoxetine or placebo along with cognitive behavioral therapy (CBT) for 1 year. Clinical, demographic and psychometric variables were assessed after weight restoration prior to randomization and putative predictors of successful weight maintenance at 6 and 12 months were examined. RESULTS: The most powerful predictors of weight maintenance at 6 and 12 months following weight restoration were pre-randomization body mass index (BMI) and the rate of weight loss in the first 28 days following randomization. Higher BMI and lower rate of weight loss were associated with greater likelihood of maintaining a normal BMI at 6 and 12 months. An additional predictor of weight maintenance was site; patients in Toronto fared better than those in New York. CONCLUSIONS: This study found that the best predictors of weight maintenance in weight-restored AN patients over 6 and 12 months were the level of weight restoration at the conclusion of acute treatment and the avoidance of weight loss immediately following intensive treatment. These results suggest that outcome might be improved by achieving a higher BMI during structured treatment programs and on preventing weight loss immediately following discharge from such programs.

Eating disorders: progress and problems.

Recent research on Anorexia Nervosa and Bulimia Nervosa has yielded an increasingly detailed understanding of the range of biological and psychological abnormalities associated with these eating disorders. Inherited vulnerabilities, cultural pressures, and adverse individual and family experiences all appear to contribute to the onset of extreme dieting, binge eating, and purging. Once initiated, these behaviors give rise to multiple physiological disturbances, some of which may serve to perpetuate the illness. Although there have been substantial advances in the management of Bulimia Nervosa, the goal of offering effective treatment to all individuals with eating disorders remains elusive. This article reviews current thinking on the etiology and treatment of the two major eating disorders and a related syndrome, Binge Eating Disorder.

Cigarette craving, smoking withdrawal, and clonidine.

Clonidine, an alpha-2-adrenergic agonist, significantly reduces opiate withdrawal. Fifteen heavy smokers abstained from cigarettes on three separate occasions and received instead clonidine, placebo, or the benzodiazepine alprazolam. Clonidine and alprazolam diminished withdrawal symptoms. The two drugs suppressed anxiety, tension, irritability, and restlessness equally but clonidine had a greater effect than alprazolam on cigarette craving. These observations suggest that noradrenergic activity is a common feature in the pathophysiology of withdrawal and that a special relationship exists between central noradrenergic activity and craving.

Modified sham feeding of sweet solutions in women with and without bulimia nervosa.

Although it is possible that binge eating in humans is due to increased responsiveness of orosensory excitatory controls of eating, there is no direct evidence for this because food ingested during a test meal stimulates both orosensory excitatory and postingestive inhibitory controls. To overcome this problem, we adapted the modified sham feeding technique (MSF) to measure the orosensory excitatory control of intake of a series of sweetened solutions. Previously published data showed the feasibility of a "sip-and-spit" procedure in nine healthy control women using solutions flavored with cherry Kool Aid and sweetened with sucrose (0-20%). The current study extended this technique to measure the intake of artificially sweetened solutions in women with bulimia nervosa (BN) and in women with no history of eating disorders. Ten healthy women and 11 women with BN were randomly presented with cherry Kool Aid solutions sweetened with five concentrations of aspartame (0, 0.01, 0.03, 0.08 and 0.28%) in a closed opaque container fitted with a straw. They were instructed to sip as much as they wanted of the solution during 1-minute trials and to spit the fluid out into another opaque container. Across all subjects, presence of sweetener increased intake (p<0.001). Women with BN sipped 40.5-53.1% more of all solutions than controls (p=0.03 for total intake across all solutions). Self-report ratings of liking, wanting and sweetness of solutions did not differ between groups. These results support the feasibility of a MSF procedure using artificially sweetened solutions, and the hypothesis that the orosensory stimulation of MSF provokes larger intake in women with BN than controls.

Who seeks bariatric surgery? Psychosocial functioning among adolescent candidates, other treatment-seeking adolescents with obesity and healthy controls.

Limited data are available on the characteristics of adolescents with obesity who seek bariatric surgery. Existing data suggest that adolescent surgery candidates have a higher body mass index (BMI) than comparison adolescents with obesity, but the limited findings regarding psychosocial functioning are mixed. This study aimed to compare BMI and psychosocial functioning among adolescent bariatric surgery candidates, outpatient medical-treatment-seeking adolescents with obesity (receiving lifestyle modification), and adolescents in the normal-weight range. All adolescents completed self-report measures of impulsivity, delay discounting, depression, anxiety, stress, eating pathology, family functioning and quality of life, and had their height and weight measured. Adolescent surgical candidates had higher BMIs than both comparison groups. Surgical candidates did not differ from medical-treatment-seeking adolescents with obesity on any measure of psychosocial functioning, but both groups of adolescents with obesity reported greater anxiety and eating pathology and poorer quality of life than normal-weight adolescents. Quality of life no longer differed across groups after controlling for BMI, suggesting that it is highly related to weight status. Adolescents with obesity may experience greater anxiety, eating pathology, and quality of life impairments than their peers in the normal-weight range regardless of whether they are seeking surgery or outpatient medical treatment. Clinical implications and directions for future research are discussed.

Intake, sweetness and liking during modified sham feeding of sucrose solutions.

Although sweet solids and liquids are palatable to humans and ingested frequently when readily available, the quantitative relationship between sweet taste and intake has not been reported in humans. To investigate the quantitative relationship between sweet taste and intake directly, we adapted the modified sham feeding technique, previously used in humans for the study of the orosensory control of autonomic, neuroendocrine, and metabolic mechanisms, to measure the intake of solutions both unsweetened and sweetened with four concentrations of sucrose. By limiting the sucrose stimuli to the mouth, the modified sham feeding technique measures the orosensory stimulation of intake by sucrose in the absence of inhibitory postingestive stimulation. Nine healthy women were randomly presented with two series of five solutions of cherry Kool Aid unsweetened or sweetened with one of four concentrations of sucrose (2.5%, 5%, 10%, or 20%) in a closed opaque container fitted with a straw. They were instructed to sip as much as they wanted of the liquid during 2-min trials and to spit the fluid out into another opaque container. At the end of each trial, they used Visual Analogue Scales to rate the perceived intensities of sweetness and liking of the liquid that they had just sipped and spit. Intake, liking and perceived sweetness were significantly affected by sucrose concentration (p values

An open trial of an intensive summer day treatment program for severely overweight adolescents.

This open trial examined the feasibility and usefulness of treating adolescents with a body mass index (BMI) > or =95th percentile in a 6-week day treatment program within a psychiatric outpatient setting. Sixteen adolescents, ages 12-15, attended a 6-week multidisciplinary summer day treatment program. Outcome measures include pre- and post-program assessments of BMI, body fat, laboratory measures, nutritional status, physical activity, mood and eating disorder symptoms, motivation, self-esteem and quality of life. BMI, waist/hip circumferences, blood pressure, heart rate, and body fat did not change significantly from baseline to week 6. Fasting glucose decreased significantly from baseline to week 6, but there were no significant changes in other laboratory measures. The teen-rated feelings subscale of the Peds Quality of Life Scale improved. Self-esteem, as measured by the Rosenberg Self- Esteem Scale, indicated a strong trend towards improvement, and motivation measures also showed a trend for improvement. These findings suggest that a brief, intensive intervention for overweight adolescents may yield meaningful changes in quality of life, self-esteem, and motivation, even in the absence of significant weight loss.

Eating behavior of women with bulimia.

To obtain objective information about binge- and non-binge-eating behavior, 12 women with bulimia and ten women without eating problems (controls) were asked to eat four meals in a structured laboratory setting, on separate nonconsecutive days. The same instructions were given to both groups. On two days, they were asked to eat a normal amount, and on two days, they were asked to eat as much as they could, ie, to binge. For each type of instruction, they were given a single- and a multiple-course meal. The patients ate significantly more than the controls when asked to binge, both on the multiple-course meals that they rated as typical of binges and on the single-course meals. When they were asked to eat normally, there was no significant difference in intake between patients and controls on either single- or multiple-course meals. After all meals, hunger ratings of patients were significantly higher than hunger ratings of controls. There was also a significant positive correlation between intakes of single- and multiple-course binge meals and an inverse correlation between intake of multiple-course binge meals in bulimic patients and their rating of how well they controlled their eating. Thus, a structured laboratory eating situation can be used to reveal differences between bulimic and normal individuals and has the potential for assessing clinical status and exploring mechanisms responsible for binge eating.

Tricyclic antidepressants in depressed patients with cardiac conduction disease.

The observation that fatalities from tricyclic antidepressant (TCA) overdose are associated with heart block and/or arrhythmias has led to concern about the cardiovascular effects of TCAs. Contrary to expectations, studies have shown TCAs to be relatively safe in patients without heart disease. However, it is unclear whether these drugs are also safe in patients with heart disease. This prospective study compared the risk of cardiovascular complication at therapeutic plasma concentrations of TCAs in 196 depressed patients, 155 with normal electrocardiograms and 41 with either prolonged PR interval and/or bundle-branch block. The prevalence of second-degree atrioventricular block was significantly greater in patients with preexisting bundle-branch block (9%) than in patients with normal electrocardiograms (0.7%). Orthostatic hypotension occurred significantly more frequently with imipramine than with nortriptyline, and in patients with heart disease.

Phenelzine vs placebo in 50 patients with bulimia.

To examine the efficacy of the monoamine oxidase inhibitor phenelzine sulfate in the treatment of bulimia, a double-blind, placebo-controlled trial was conducted. In 50 women who completed the trial, phenelzine was significantly superior to placebo in the reduction of binge frequency (64% vs 5%), in the fraction of patients who had ceased bingeing at the end of the trial (35% vs 4%), and in several measures of psychological state. The superiority of phenelzine over placebo was not confined to a depressed subgroup of patients. Although no patient experienced a hypertensive crisis during the study, other side effects of phenelzine were problematic and limit the usefulness of phenelzine in this population.

Treatment of bulimia with phenelzine. A double-blind, placebo-controlled study.

Twenty bulimic women of normal weight participated in a double-blind trial studying the effects of a monoamine oxidase inhibitor (MAOI). Nine women received phenelzine sulfate and 11 received placebo. Although phenelzine's side effects were a problem, the phenelzine-treated patients reported significantly fewer binges per week and had a lower Eating Attitudes Test score. Five of the nine phenelzine-treated patients ceased binging entirely and the other four reduced their binge frequency by at least 50%; none of the 11 placebo-treated patients stopped binging and only two reduced their binge frequency by 50% or more. These data demonstrate that phenelzine is significantly more effective than placebo in the treatment of bulimic women of normal weight and suggest a place for MAOIs in the treatment of bulimic patients capable of maintaining a tyramine-free diet.

Dexamethasone suppression test and plasma dexamethasone levels in bulimia.

A 1-mg dexamethasone suppression test (DST) was carried out in 66 women with bulimia and in 26 age- and sex-matched controls. Blood samples were obtained at 4 PM on the day following dexamethasone ingestion, and levels of cortisol and of dexamethasone in the plasma were measured. Thirty-two percent of the patients vs only 7% of the controls had plasma cortisol levels of 140 nmol/L (5 micrograms/dL) or greater following the DST (a positive DST). The plasma levels of dexamethasone varied substantially, and there was a significant inverse relationship between the plasma level of cortisol and that of dexamethasone. Patients with positive DST results had lower levels of plasma dexamethasone than did those with negative DST results, and the mean plasma level of dexamethasone was lower in the bulimic group than in the control group. These results suggest that factors other than a disturbance of hypothalamic-pituitary-adrenal activity may contribute to positive DST results in bulimia.

Uncommon troubles in young people: prevalence estimates of selected psychiatric disorders in a nonreferred adolescent population.

A two-stage epidemiologic strategy was used to estimate the lifetime prevalence of selected DSM-III-defined psychiatric disorders in a county-wide secondary school population (N = 5596). Screening tests used in the first stage included items based on DSM-III criteria for eating disorders and panic disorder, as well as the Leyton Obsessional Inventory-Child Version and the Beck Depression Inventory. Based on interviews (n = 356) by clinicians in the second stage, the lifetime prevalence of anorexia nervosa was 0.2%; bulimia, 2.5%; panic disorder, 0.6%; obsessive-compulsive disorder, 1.9%; major depression, 4.0%; dysthymic disorder, 4.9%; and generalized anxiety disorder, 3.7%. While rates of mental health service utilization varied greatly by diagnosis, only 41% of students who were assigned both a diagnosis and a rating of impairment had received any kind of clinical attention.

Metabolic abnormalities in bulimia nervosa.

Resting metabolic rate was measured in a group of 22 women of normal body weight with bulimia nervosa and in 19 age-, sex-, and weight-matched control subjects. Mean resting metabolic rate of patients was significantly lower than that of controls (5162 +/- 928 vs 5636 +/- 449 kJ/24 h [1229 +/- 221 vs 1342 +/- 107 kcal/24 h]), as was mean fasting blood glucose level (4.0 +/- 0.6 vs 4.6 +/- 0.6 mmol/L). Mean basal thyrotropin level was significantly lower in patients than controls, but other thyroid indexes did not differ. There were no group differences in body fat mass, fat cell size, or lipoprotein lipase activity. These data suggest that there is a disturbance in energy regulation in bulimia nervosa. However, the origins and role of this disturbance in the pathophysiology of bulimia are unclear.

Recognition of streptococcal pharyngitis in adults.

In order to devise a strategy for the management of acute pharyngitis, the clinical features of 418 adults with sore throat were noted and throat cultures were obtained. Patients with cultures positive for group A beta-hemolytic streptococci had a significantly higher (P less than or equal to .01) frequency of recent exposure to streptococcal infection, pharyngeal exudate, enlarged or tender cervical nodes, and high fever (greater than or equal to 38.3 C [101 F]. Patients with negative cultures complained more frequently of cough. On the basis of these symptoms and signs, a clinical algorithm was developed and discriminant function scores were computed that identify patient populations with different probabilities of having streptococcal pharyngitis. The patients with moderate and high probabilities included 91% of patients with positive cultures but only 67% of the total patient population. These methods could be the basis for more efficient evaluation of adults with sore throat.

The production rate of cortisol declines during recovery from anorexia nervosa.

The plasma concentration of cortisol is elevated in many patients with anorexia nervosa. It has remained unclear whether this elevation of plasma cortisol level is due only to a slowing of the rate of cortisol metabolism or whether there is, as well, an increase in adrenal secretory activity in anorexia nervosa. We studied adrenocortical activity in 9 female patients and one male patient with anorexia nervosa before and during recovery. The 24-h mean level of plasma cortisol and the rate of urinary free cortisol excretion decreased during recovery, from 11.4 to 7.4 micrograms/dl and from 225 to 116 micrograms/day, respectively (P less than 0.005 and P less than 0.10, paired t test). These changes were associated with a significant decline in the rate of cortisol production from 24.3 to 17.9 mg/day as measured by radioisotope dilution (P less than 0.005). These results suggest that adrenal secretory activity is increased in anorexia nervosa and that the elevation of plasma cortisol level observed in this syndrome reflects not only a slowing of cortisol metabolism but also a rise in cortisol production.

Behavioral and neuroendocrine responses to metaCPP in anorexia nervosa.

In response to the partial serotonin agonist meta-chlorophenylpiperazine (metaCPP), patients with obsessive-compulsive disorder have been reported to exhibit an increase in obsessive symptoms and a diminished release of prolactin and/or cortisol compared to controls. We examined the response to metaCPP of 10 patients with anorexia nervosa, before and after weight gain, and of eight healthy controls. Prior to weight gain, the patients exhibited a greater behavioral response to metaCPP than the controls and diminished prolactin and cortisol responses. Only the prolactin abnormality persisted after weight gain. These observations suggest that, in patients with anorexia nervosa, weight loss is associated with the development of neurobiological disturbances which are in some ways similar to those of obsessive-compulsive disorder.

EEG-monitored sleep in anorexia nervosa and bulimia.

We compared the EEG-monitored sleep of 8 women with anorexia nervosa and 16 normal weight women with bulimia to that of 14 normal women. The patients with anorexia nervosa spent less time asleep and spent less of their sleep time in Stage 1. The sleep of the normal weight patients with bulimia was remarkably similar to that of the controls. These data suggest that most patients with anorexia nervosa and bulimia do not exhibit the type of sleep disturbances characteristic of patients with major depressive illness.