Lisdexamfetamine Pharmacokinetic Comparison Between Patients Who Underwent Roux-en-Y Gastric Bypass and Nonsurgical Controls.

INTRODUCTION/PURPOSE: The objective of this research was to characterize the impact of Roux-en-Y gastric bypass (RYGB) on the pharmacokinetic properties of the pro-drug lisdexamfetamine and its active metabolite, d-amphetamine. MATERIALS AND METHODS: A case-control design was used where patients who had undergone RYGB 9-24 months prior were matched on sex, age, and body mass index (BMI) to nonsurgical controls who had no history of weight loss surgery. Each participant received a single 50 mg dose of lisdexamfetamine, and plasma samples were collected over a 24-h period following dosing. Noncompartmental analyses were used to compare pharmacokinetic measures between groups. RESULTS: There were no significant differences between the RYGB (n = 10) and NSC groups (n = 10) on sex (70% female), age (40.9 ± 9.6 vs. 41.3 ± 8.9 years), BMI (30.3 ± 5.2 vs. 31 ± 5.9 kg/m2), or ethnicity (100% vs. 80% White). The pharmacokinetic parameters between the RYGB and NCS groups were found to be equivalent for lisdexamfetamine and d-amphetamine, including maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC(0-∞)). CONCLUSION: These data suggest that there is no need to routinely adjust lisdexamfetamine dosing following RYGB. However, given the potential for inter-individual differences, patients who undergo RYGB should be clinically monitored and individualized dosing strategies should be considered for concerns surrounding efficacy or toxicity.

Comfort Level and Barriers to the Appropriate Use of Clozapine: a Preliminary Survey of US Psychiatric Residents.

OBJECTIVE: Clozapine is the gold standard treatment for treatment-resistant schizophrenia. Prior surveys of mental health providers have identified multiple causes for underutilization of clozapine; however, no previous survey has been conducted to assess US psychiatry residents' level of comfort in prescribing clozapine. METHODS: A survey was sent via email to program directors of Accreditation Council for Graduate Medical Education-affiliated psychiatry residency programs requesting the survey to be distributed to current residents. The survey included questions regarding demographics, clozapine-prescribing practices, comfort levels with prescription, and perceived barriers to prescription. RESULTS: A total of 164 psychiatric residents completed the survey, 37% PGY-1 and 2 residents and 63% PGY-3 or higher. One-third of the respondents had a clozapine clinic in their program. Only 18% of the residents felt "very" comfortable in initiating clozapine and 41% felt "somewhat" comfortable. Two main reasons for not starting clozapine were (1) side effect profile (41%) and (2) limited experience and inadequate training in clozapine use (38%). More than 4/5ths of the residents (83%) responded that they would feel more comfortable in prescribing clozapine if they were trained in a clozapine clinic. Major limitation of this study has been the small sample size, lack of representativeness, and generalization. CONCLUSIONS: Forty-one percent of the respondents did not feel comfortable with clozapine prescription. Major concerns cited included the side effect profile as well as lack of experience and training. The majority of the respondents felt that they would be more comfortable prescribing clozapine if they had the opportunity to train in a clozapine clinic.

Clozapine augmentation strategies.

Clozapine is established as the gold standard for antipsychotic treatment of patients suffering from treatment-resistant schizophrenia. Over virtually 3 decades, the level of inadequate response to clozapine was found to range from 40% to 60%. A heightened interest developed in the augmentation of clozapine to try to achieve response or maximize partial response. A large variety of drug groups have been investigated. This article focuses on the meta-analyses of these trials to discover reasonable evidence-based approaches to the management of patients not responding to clozapine.

Psychopharmacology and Bariatric Surgery.

Currently, it has been demonstrated that psychotropic drugs, particularly antidepressants, are frequently prescribed for patients who seek bariatric surgery. Many bariatric surgery patients have a history of a mood disorder. Unlike medications for diabetes, hypertension or hyperlipidemia, which are generally reduced and at times discontinued, postsurgery antidepressants use is only slightly reduced. The Roux-en-Y procedure is most frequently associated with alteration in drug exposure. Medication disintegration, dissolution, absorption, metabolism and excretion have been found to be altered in postbariatric patients, although data are sparse at this time. This paper will review the current evidence regarding the effect of bariatric surgery on drug treatment including mechanism of interference as well as the extent of changes identified to date. Data will be presented as controlled trials followed by case series and reports.

Hepatic pathology among patients without known liver disease undergoing bariatric surgery: observations and a perspective from the longitudinal assessment of bariatric surgery (LABS) study.

Liver biopsy is not routine during bariatric surgery. Alanine aminotransferase (ALT) is widely used to screen for liver disease. We assessed the relationship between ALT and pathology in biopsies from Longitudinal Assessment of Bariatric Surgery (LABS) patients with normal preoperative ALTs. Biopsies from the LABS-1 and LABS-2 studies were scored using the NASH CRN and Ishak systems. Diagnosis and histology were examined in relation to alanine aminotransferase (ALT) values. Six-hundred ninety-three suitable biopsies were evaluated. Biopsied patients had a median age of 45 years; 78.6% were female and 35.1% diabetic; median body mass index was 46 kg/m(2). Six-hundred thirty-five biopsied patients had preoperative ALTs. Median ALT was 25 IU/L (interquartile range [IQR] 19-36 IU/L); 26.6% had an ALT > 35 IU/L and 29.9% exceeded the more restrictive Prati criteria for normal. Using the Prati criteria, 7.9% of participants with normal ALT had steatohepatitis and 5.3% had ≥ stage 2 fibrosis. Logistic regression models were used to predict the probabilities of having bridging fibrosis/cirrhosis or a diagnosis of borderline/definite steatohepatitis in the unbiopsied LABS-2 sample. The proportion of biopsied participants with these findings was very similar to the modeled results from the unbiopsied cohorts. We estimated that 86.0% of participants with advanced fibrosis and 88.1% of participants with borderline/definite steatohepatitis were not biopsied and went undiagnosed. As ALT did not reliably exclude significant obesity-related liver disease in bariatric surgery patients, consideration should be given to routine liver biopsy during bariatric surgery and medical follow-up of significant hepatic pathology.

A comparison of duloxetine plasma levels in postbariatric surgery patients versus matched nonsurgical control subjects.

BACKGROUND: Bariatric surgery such as the Roux-en-Y gastric bypass (RYGB) is currently used as a treatment for severe obesity. Alteration of the gastrointestinal tract by this procedure suggests a potential for clinically significant alterations in the bioavailability of ingested medications including antidepressants. OBJECTIVES: The purpose of this trial was to determine to what extent the RYGB procedure alters the area under the plasma concentration/time curve (AUC(0-infinity)) of the antidepressant, duloxetine. METHODS: Ten subjects who were 1 year post-RYGB where compared with healthy control subjects matched for body mass index, age, and sex. Ultrarapid or poor metabolizers for cytochrome P450 2D6 were excluded from the study. Subjects received a single dose of 60 mg of duloxetine. Nineteen plasma samples were obtained during 72 hours to characterize the plasma level profile. RESULTS: The mean AUC(0-infinity) was significantly smaller for the postbariatric surgery (PBS) group (646.74 ng × h/mL [SD, 79.70; range, 539.57-791.62], P = 0.017) compared to the nonsurgical control group (1119.91 ng × h/mL [SD, 593.40; range, 415.5-2426.56]). The Tmax was also significantly shorter for the PBS group (2.2 hours) compared to the nonsurgical control group (6 hours; P = 0.005). No significant difference in Cmax or half-life was identified. CONCLUSIONS: To our knowledge, this is the first reported study exploring duloxetine pharmacokinetics PBS. This trial found that the bariatric surgery group was exposed to only 57.7% of duloxetine as compared to the nonsurgery group. This finding suggests that clinicians need to monitor patients closely after bariatric surgery and that further exploration of the effects of bariatric surgery on antidepressant pharmacokinetic parameters is warranted.

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.

Possible risk factors for increased suicide following bariatric surgery.

OBJECTIVE: 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. DESIGN AND METHODS: The purpose of this report is to review this literature and to review possible risk factors for increased suicidal risk following bariatric surgery, to delineate future research directions. RESULTS: First a variety of medical, biological, and genetic factors, including the persistence or recurrence of medical comorbidities after bariatric surgery, the disinhibition and impulsivity secondary to changes in the absorption of alcohol, hypoglycemia, as well as pharmacokinetic changes that may affect the absorption of various medications including antidepressant medications are reviewed. Also reviewed are possible mediating factors involving changes in various peptidergic systems such as GLP-1 and Ghrelin. A number of psychosocial issues that might be involved are discussed, including lack of improvement in quality of life after surgery, continued or recurrent physical mobility restrictions, persistence or recurrence of sexual dysfunction and relationship problems, low self-esteem, and a history of child maltreatment. Inadequate weight loss or weight regain are also discussed. CONCLUSIONS: A number of possible contributing factors have been identified. Possible theoretical models involved and directions for research are suggested.

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.

Atypical antipsychotic-induced weight gain: insights into mechanisms of action.

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 for SGA-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-HT(2C) 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 H(1), 5-HT(2A), 5-HT(2C), muscarinic M(3) 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.

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.

An exploration of the effect of modafinil on olanzapine associated weight gain in normal human subjects.

BACKGROUND: Weight gain has been associated with many second generation antipsychotics (SGAs). A variety of theories have been put forward as to the etiology of SGA-associated weight gain. Modafinil possesses pharmacologic effects that could influence the weight gain associated with SGAs. The objective of this trial was to determine the effect of modafinil on olanzapine-associated weight gain. METHODS: This study was a 3-week, randomized, double-blind, placebo-controlled trial. All subjects received olanzapine titrated to 10 mg/day. Concurrently, subjects were randomized to receive modafinil titrated to 200 mg/day or placebo. Weight and feeding lab assessments were conducted at baseline and endpoint. RESULTS: Fifty subjects were enrolled in the study with 20 subjects per group completing the trial. The primary outcome variable was change in the body mass index (BMI) over the 3 weeks of the trial. Increases in BMI were observed in both groups. However, analysis of covariance, controlled for baseline BMI, revealed that the olanzapine/placebo group had a greater increase in BMI at end point compared with the olanzapine/modafinil group (.89 +/- .59 vs. .47 +/- .50 kg/m(2), p < .05). When controlled for gender, the comparison showed a significant difference between groups at week 1 but not at weeks 2 or 3. CONCLUSIONS: The results of this trial should not be extrapolated to clinical practice at this time. These data do serve to support further evaluation in a patient population to determine if the weight modifying effect of modafinil can be demonstrated over a longer period of time.

What potential role is there for medication treatment in anorexia nervosa?

OBJECTIVE: To review selected issues regarding the development of drug treatments for anorexia nervosa (AN). METHOD: The existing pharmacotherapy literature for AN is reviewed, and the theoretical and practical considerations are discussed. RESULTS: A very wide variety of drugs have been examined in AN, generally with negative results. There are a number of potential reasons for this finding, including compliance, nutritional deficits, selection of the wrong targets or the wrong outcome measures, use of monotherapy, lack of animal models, or factors intrinsic to AN. CONCLUSION: Pharmacotherapy provides little benefit in the treatment of AN at present. Several strategies might lead to the identification of more effective agents, including new measurement strategies, identification of novel pharmacologic targets, and consideration of a clinical trials network.

A comparison of the effects of olanzapine and risperidone versus placebo on ghrelin plasma levels.

To thoroughly investigate the phenomenon of atypical antipsychotic-associated weight gain, a feeding laboratory paradigm was developed that included obtaining plasma levels of the orexigenic peptide ghrelin that is associated with appetite and eating. This study is a randomized, double-blind, parallel group trial comparing the effects of a 2-week exposure to olanzapine, risperidone, or placebo on plasma ghrelin area under the plasma-time curve (AUC) in 28 healthy human subjects. Subjects were randomized to receive olanzapine, risperidone, or placebo and titrated over 4 days to 10 mg/d or 4 mg/d, respectively. The mean dose at end point was 8.6 + 1.8 mg/d for the olanzapine group and 2.8 + 0.8 mg/d for the risperidone group. Weight changes were significantly different between groups at end point (F2,44 = 10.193; P = 0.0001). The olanzapine group demonstrated a significant increase in weight at end point (2.25 + 1.84 kg) compared with placebo (0.13 + 1.05 kg; P = 0.007). Because of the small subject number, the comparisons between olanzapine and risperidone and risperidone and placebo did not reach statistical significance, although olanzapine's mean weight gain was numerically greater than that of risperidone (2.25 + 1.84 kg vs 1.10 + 0.99 kg) and risperidone's mean weight gain was numerically larger than placebo (1.10 + 0.99 kg vs 0.13 + 1.05 kg). The baseline adjusted Bonferroni corrected contrast of end point ghrelin AUC demonstrated a significant difference between groups (F2,24 = 4.40; P = 0.024), and the post hoc analysis revealed a significant decrease in ghrelin AUC for the olanzapine group in comparison with the risperidone group (P = 0.021) but not between risperidone and placebo or olanzapine and placebo. Ghrelin AUC values did not change significantly from baseline to end point in either of the other 2 groups. The difference between groups approached but did not reach significance (F2,23 = 3.299; P = 0.055) when body mass index change was included as a covariate, suggesting that the difference in ghrelin AUC change followed the change in body weight. Sedation associated with both active drugs (P = 0.006) and "stuffy nose" associated with risperidone (P = 0.020) were the only statistically different adverse reactions when compared with placebo. Thus, a human feeding laboratory paradigm using a brief exposure to atypical antipsychotics functions as a method to investigate pharmacologically induced weight gain and its association with changes in the orexigenic peptide ghrelin. This rejects the hypothesis that ghrelin levels are elevated by the antipsychotic and that this is a potential cause of the weight gain phenomenon.

The eating disorders medicine cabinet revisited: a clinician's guide to ipecac and laxatives.

OBJECTIVE: To describe the frequency of alternative medication use in bulimia nervosa (BN), and to review available nonprescription emetic (ipecac) and laxative products and their potential toxicities. METHOD: Survey data were collected from 39 consecutive treatment-seeking patients with BN or subthreshold BN. Survey data of the available nonprescription and herbal products from local retail stores were also collected. Toxicology information was reviewed on these agents from MEDLINE and herbal textbooks. RESULTS: Ipecac use occurred in 18% of the 39 patients. Laxatives had been used at some point to control weight or "get rid of food" by 67% of the patients. Of these, 31% had abused laxatives during the month prior to evaluation. In the product survey, 248 laxative-containing products were identified. CONCLUSION: There are numerous laxative products readily available to patients, and many of them have significant associated toxicities. Patients with BN tend to endorse high rates of laxative use. While ipecac is used infrequently, it can have deleterious consequences. Patients with BN should be screened for use of both ipecac and laxatives and should be educated about the potential consequences associated with the misuse of these agents.

A survey of herbal and alternative medication use among participants with eating disorder symptoms.

OBJECTIVE: The purpose of this survey was to collect data on herbal use in participants with eating disorder symptoms. METHOD: A survey was administered to 100 participants who had either sought treatment at the Eating Disorder Institute (EDI) or had been enrolled in previous research as the result of eating disorder symptoms. RESULTS: Of the 100 participants, 64% used an herbal product for weight loss. The mean monthly expenditure on herbs over the past year was 33.88 dollars +/- 41.10 dollars, with a range of 2 dollars-200 dollars. Dexatrim (Chattem, Chattanooga, TN; N = 27) and St. John's Wort (N = 19) had the highest reported use. Magazines were the most common source of product information (38.3%), with health care professionals being reported less frequently as the source of information. Knowledge of ephedra-related adverse effects was variable, and depended on a previous history of use. The majority (62.3%) of herb users reported an adverse effect. CONCLUSION: Herbal use is frequent among those with eating disorder symptoms, often resulting in substantial financial cost. Health professionals are rarely the source of herbal information. Therefore, there is ample room for educational interventions, which may result in the safer use of herbal products.

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, beta3-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.

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

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 + 1.62 kg, 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.

New targets in the treatment of anorexia nervosa.

The pathophysiology of anorexia nervosa (AN) is complex and involves alterations of serotonin, dopamine and histamine neurotransmitters. In addition, receptor activity is disturbed, presumably in response to the neurotransmitter changes. These alterations are reviewed in relation to symptomatology and outcome of AN. Neuropeptide and peripheral orexigenic and satiety peptide research is in its infancy but holds much promise to shed light on the pathophysiological mechanisms involved in this illness. Current drug therapies have not demonstrated the efficacy desired in the treatment of AN. Current therapies are reviewed and new drug targets are explored. Compounds that interact with serotonin, histamine and dopamine receptors may offer unique treatment opportunities. In the future, the manipulation of peptides may add to the therapeutic potential of pharmacotherapy.