James L. Roerig

Health-Related Quality of Life in Morbidly Obese Patients: Effect of Gastric Bypass Surgery

Background: The effect of gastric bypass on the health-related quality of life (HRQoL) of morbidly obese patients was investigated in a cross-sectional study. Methods: A postoperative group of 78 patients on average 13.8 years after gastric bypass was compared with a preoperative control group of 110 patients. The SF-36 was used to assess HRQoL. In preoperative patients, the SF-36 was self-administered, while in the postoperative group, telephone interviews were conducted. In the postoperative sample, multiple stepwise linear regression analyses were carried out to examine putative predictors of the physical (PCS) and the mental (MCS) composite scores of the SF-36. Results: Significant differences between the preand postoperative group were found for all subscales except Mental Health, in favor of the postoperative group. On average 13.8 years after gastric bypass, most of the sub-scales were similar to the US norm values. However, the Bodily Pain and the overall Physical Composite scale (PCS) scores were lower (more impaired) in the postoperative group compared with the US norms. Female patients, patients who were hospitalized since the surgery, and those who had lost less weight had more impaired values on the PCS and patients who reported binge-eating disorder (BED) at follow-up had more impaired values on the Mental Composite Scale (MCS) of the SF-36. Conclusion: HRQoL was significantly better in postoperative gastric bypass patients in comparison to a sample of preoperative patients. However, HRQoL, specifically the physical domain of the SF-36, was more impaired in long-term follow-up patients compared with US norm values. The reoccurrence of BED after surgery negatively influenced the mental domain of the SF-36.

Atypical Antipsychotic-Induced Weight Gain

Prescriptions for second-generation antipsychotics (SGAs) have surpassed those for first-generation agents in the treatment of schizophrenia and bipolar disorder. While SGAs have the benefit of a much reduced risk of causing movement disorders, they have been associated with weight gain and metabolic effects. These adverse reactions are not uncommon, and threaten to have a significant impact on the patient’s health over the long-term treatment that the patient requires. Currently, the aetiology of these effects is not known. This article reviews the data exploring the weight gain phenomenon. The literature was reviewed from searches of PubMed and the references of major articles in the field. The SGAs present a heterogeneous risk for weight gain. In addition, different individuals receiving the same drug can exhibit substantially different weight changes. This pattern suggests that a group of factors are associated with the weight gain phenomenon rather than a single mechanism. Coupled with the genetic profile that the patient brings to the treatment, the risk forSGA-induced weight gain will be different for different drugs and different individuals. Targets for exploration of the weight gain phenomenon include receptor interactions involving serotonin, histamine, dopamine, adrenergic, cannabinoid and muscarinic receptors. The association of SGA-induced weight gain and the role of orexigenic and anorexigenic peptides are reviewed. Also, a brief discussion of genetic factors associated with SGA-induced weight gain is presented, including that of the serotonin 5-HT2C receptor gene (HTR2C) and the cannabinoid 1 receptor gene (CNR1).The most promising data associated with SGA-induced weight gain include investigations of the histamine HP1, 5-HT2A, 5-HT2C, muscarinic M3 and adrenergic receptors. In addition, work in the genetic area promises to result in a better understanding of the variation in risk associated with different individuals.

Possible risk factors for increased suicide following bariatric surgery

There is a growing research literature suggesting that there may be elevated risk of suicide following bariatric surgery. Most of the data reported thus far has been cross‐sectional and observational, and very little is known about the possible specific causal variables involved.

Laxative abuse: epidemiology, diagnosis and management.

Laxatives have been used for health purposes for over 2000 years, and for much of that time abuse or misuse of laxatives has occurred. Individuals who abuse laxatives can generally be categorized as falling into one of four groups. By far the largest group is made up of individuals suffering from an eating disorder such as anorexia or bulimia nervosa. The prevalence of laxative abuse has been reported to range from approximately 10% to 60% of individuals in this group. The second group consists of individuals who are generally middle aged or older who begin using laxatives when constipated but continue to overuse them. This pattern may be promulgated on certain beliefs that daily bowel movements are necessary for good health. The third group includes individuals engaged in certain types of athletic training, including sports with set weight limits. The fourth group contains surreptitious laxative abusers who use the drugs to cause factitious diarrhoea and may have a factitious disorder.Normal bowel function consists of the absorption of nutrients, electrolytes and water from the gut. Most nutrients are absorbed in the small intestine, while the large bowel absorbs primarily water. There are several types of laxatives available, including stimulant agents, saline and osmotic products, bulking agents and surfactants. The most frequently abused group of laxatives are of the stimulant class. This may be related to the quick action of stimulants, particularly in individuals with eating disorders as they may erroneously believe that they can avoid the absorption of calories via the resulting diarrhoea.Medical problems associated with laxative abuse include electrolyte and acid/base changes that can involve the renal and cardiovascular systems and may become life threatening. The renin-aldosterone system becomes activated due to the loss of fluid, which leads to oedema and acute weight gain when the laxative is discontinued. This can result in reinforcing further laxative abuse when a patient feels bloated and has gained weight.Treatment begins with a high level of suspicion, particularly when a patient presents with alternating diarrhoea and constipation as well as other gastrointestinal complaints. Checking serum electrolytes and the acid/base status can identify individuals who may need medical stabilization and confirm the severity of the abuse. The first step in treating laxative misuse once it is identified is to determine what may be promoting the behaviour, such as an eating disorder or use based on misinformation regarding what constitutes a healthy bowel habit. The first intervention would be to stop the stimulant laxatives and replace them with fibre/osmotic supplements utilized to establish normal bowel movements. Education and further treatment may be required to maintain a healthy bowel programme. In the case of an eating disorder, referral for psychiatric treatment is essential to lessen the reliance on laxatives as a method to alter weight and shape.

Preliminary comparison of sertraline levels in postbariatric surgery patients versus matched nonsurgical cohort.

BACKGROUND Roux-en-Y gastric bypass (RYGB) is the most frequent bariatric procedure performed in the United States, with thousands performed. Because of the changes to the gastrointestinal tract, the potential exists for clinically significant alterations in the absorption/bioavailability of ingested medications. The purpose of the present pilot trial was to determine to what extent RYGB alters the area under the plasma concentration/time curve (AUC(0-10.5)) of the antidepressant, sertraline at a community research center. METHODS After an overnight fast, 5 postbariatric surgery and 5 nonsurgical control subjects matched for body mass index, age, and gender received 100 mg of sertraline. Plasma samples were obtained for 10.5 hours. The mean AUC(0-10.5), maximal plasma concentration, and the interval to the peak plasma level were obtained for both groups. RESULTS The mean AUC(0-10.5) was significantly smaller for the postbariatric surgery group (124.4 ± 55.5 ng-hr/mL, range 62.0-198.1; P = .043) compared with the nonsurgical control group (314.8 ± 129.6 ng-hr/mL, range 194.8-508.7). The maximal plasma concentration was also significantly smaller for the postbariatric surgery group than for the nonsurgical control group (P = .043). CONCLUSION To our knowledge, this is the first reported study exploring antidepressant pharmacokinetics after bariatric surgery. In the present trial, the AUC(0-10.5) and maximal plasma concentration were significantly smaller in the subjects who had undergone RYGB than in the matched subjects who had not. Additional investigation of the effects of bariatric surgery (RYGB, sleeve gastrectomy, and gastric banding) on the antidepressant pharmacokinetic parameters is warranted.

Drug therapy for patients with eating disorders.

The purpose of this article is to review the psychopharmacology treatment literature for patients with eating disorders including bulimia nervosa, anorexia nervosa and binge eating disorder. The best-developed treatment literature concerns bulimia nervosa, which has been studied now in several dozen pharmacological treatment studies. The agents most commonly used are the antidepressants, with particular focus on the selective serotonin reuptake inhibitors including fluoxetine hydrochloride. These agents clearly impact significantly on the frequency of abnormal eating behaviors such as binge eating and purging. However, subjects treated with these drugs rarely achieve remission. Pharmacotherapy of anorexia nervosa has also traditionally focused on the use of antidepressants and there is some evidence that the use of SSRIs may help in preventing relapse in weight restored patients. Recently interest has developed in the use of atypical neuroleptics to help with the obsessionality and resistance to treatment frequently seen in low weight patients, the most commonly employed agent being olanzapine. Pharmacotherapy of binge-eating disorder is now being intensively investigated. In general medication alone seems inferior to psychotherapy in the short term. Antidepressants can increase the amount of weight loss when combined with psychological treatment and also appear to benefit symptoms such as depression. Further data are needed, but a number of drugs appear promising.

A comparison of the effects of olanzapine and risperidone versus placebo on eating behaviors.

Abstract: To thoroughly investigate the phenomenon of atypical antipsychotic associated weight gain, a feeding laboratory paradigm was developed. This study is a randomized, double-blind, parallel group trial comparing the tolerability and effects of a two-week exposure to olanzapine, risperidone or placebo on weight, resting energy expenditure (REE), and eating behaviors in 48 healthy human subjects. Subjects were randomized to receive olanzapine, risperidone, or placebo and titrated over four days to 10 mg/d, or 4 mg/d, respectively. The mean dose at endpoint was 8.75 mg/day for the olanzapine group and 2.88 mg/d risperidone group. Weight changes were significantly different between groups at midpoint (F = 5.477, df = 2, 44, P = .0001). The olanzapine group demonstrated a significant increase in weight at midpoint (1.59 + 1.80 kg, P = .002) and endpoint (2.25 + 1.62kg, P = .0001) compared to placebo and at endpoint compared to risperidone (1.05 + 1.15 kg, P = .015). Resting energy expenditures corrected for fat free mass did not reveal any differences between groups. Olanzapine subjects demonstrated significantly more dry mouth and sedation versus placebo while risperidone subjects experienced significantly more sedation, dry mouth, dizziness stuffy nose and restlessness than placebo and more dizziness and stuffy nose versus olanzapine subjects. Thus, a human feeding lab paradigm utilizing a brief exposure to atypical antipsychotics functions as a method to investigate pharmacologically induced weight gain.

Emerging drugs for eating disorder treatment

Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) comprise the currently recognised eating disorders. Although distinct diagnostic entities, they share certain forms of comorbid psychopathology, particularly anxiety and mood disorders. BN and BED have been studied most intensively as targets for pharmacotherapy. The list of drugs tested in eating disorders is substantial; however, the number of therapeutic classes of medications tested in these conditions is relatively modest. Antidepressant medications, including tricyclic antidepressants, selective serotonin re-uptake inhibitors, as well as some of the novel antidepressants, have shown evidence of some therapeutic value in both BN and BED. Their efficacy in AN, however, has been disappointing. The pharmacological options for AN are very limited. The number of controlled trials that have been conducted is small, and the research that has been successfully completed has generally failed to demonstrate medication efficacy. Patients with BN typically show reduced binge eating and purging frequency in medication trials, but rarely attain abstinence. In BED, patients often measure the value of their medication therapy by its ability to stimulate weight loss, which is another area on which future pharmacotherapy may improve. Novel pharmacological interventions are needed for each of these conditions. Peptide hormones are increasingly being evaluated for eating disorder treatment, including ghrelin agonists, neuropeptide Y1 and -5 antagonists, orexin receptor antagonists, corticotropin-releasing factor receptor 2 antagonists, histamine 3 antagonists, melanocortin 4 receptor antagonists, β3-adrenoceptor agonists, 5-hydroxytryptamine-2A antagonists and growth hormone agonists. Although these compounds are in early phases of clinical testing for eating disorder treatments, data from these studies will be instructive in the quest for effective pharmacotherapy for these conditions. An overview of the current pharmacotherapy options for eating disorders is presented with a discussion of the emerging potential treatments.

Towards the pharmacotherapy of eating disorders.

The purpose of this review is to discuss pharmacological options for the treatment of patients with eating disorders. Sequentially described are pharmacotherapy studies of anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED). The quantity of drug trials performed with AN patients has been very limited. While the majority of studies have failed to show medication efficacy for the acute treatment of AN, there is data which suggests that fluoxetine hydrochloride may play a role in preventing relapse during maintenance therapy. Atypical antipsychotics, most often olanzapine, have shown promise in a number of uncontrolled studies. BN has been most extensively studied, with the majority of pharmacological trials focusing on antidepressants. Fluoxetine, at a dose of 60 mg/day, is FDA-approved for the treatment of BN. Psychotherapy, particularly cognitive behavioural therapy (CBT) is of well-established utility in BN and data suggests that the combination of an antidepressant plus CBT is superior to either treatment alone. Recently, there has been interest in the 5-HT3 antagonist, ondansetron, and the anticonvulsant, topiramate. BED investigators have focused largely on antidepressants, which may reduce symptoms of depression and augment psychotherapy. While sibutramine and topiramate have both been associated with weight loss in controlled trials, the former appears to be fairly well-tolerated and the latter appears to be responsible for the emergence of significant cognitive and peripheral nervous system side effects in some patients. Further pharmacological research with eating disorder patients is needed, particularly in the areas of AN and BED. Also, pharmacological augmentation strategies for those not responding to primary therapies should be explored.

Biological Therapies for Eating Disorders

OBJECTIVE To provide a comprehensive review of pharmacotherapy and other biological treatments for eating disorders. METHOD Literature on this topic was systematically reviewed. RESULTS The bulimia nervosa (BN) literature underscores the utility of antidepressants, particularly SSRIs, in improving the symptoms of the disorder. The literature on binge eating disorder supports efficacy on reduction in binge eating frequency for a variety of compounds. However, such compounds have only modest effects on weight. Certain antiepileptic agents such as topiramate, if tolerated, are probably more useful in terms of weight loss. The number of controlled trials in patients with anorexia nervosa (AN) in particular has been quite small, and recent meta-analyses show disappointing results using atypical antipsychotics in AN. DISCUSSION The pharmacological treatment of eating disorders remains an underdeveloped field although drug therapy clearly plays a role in the treatment of those with BN and binge eating disorder. Other biological therapies have not been adequately studied.