clozapine and Weight-Loss

Treatment resistance is considered a challenging problem of antipsychotic pharmacotherapy. In such cases, combination approaches are commonly used, for instance the add-on of aripiprazole to clozapine. This review aims at giving an overview of the present knowledge on this strategy. We performed a keyword-based screening of databases (including November 2007) and evaluated the data in a systematic manner. The courses of 94 patients were reported in 11 publications. At a mean dosage of 20.5 mg/day, aripiprazole achieved clinical improvement of psychotic symptoms and facilitated a dose reduction of clozapine from 476.7 to 425.1 mg/day. In parallel, clozapine serum levels decreased from 611 to 523 ng/ml. No pharmacokinetic interactions were reported, and clozapine-induced side effects ameliorated. However, single cases of extrapyramidal side effects occurred. The combination of clozapine and aripiprazole follows a neurobiological rationale and appears to be effective and tolerable. The results of placebo-controlled trials might allow further insight into the benefits and risks of this strategy.

Topics: Antipsychotic Agents; Aripiprazole; Clozapine; Drug Therapy, Combination; Humans; Piperazines; Psychotic Disorders; Quinolones; Randomized Controlled Trials as Topic; Weight Loss

Topics: Adolescent; Adult; Blood Glucose; Clozapine; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide; Female; Humans; Male; Middle Aged; Obesity; Pilot Projects; Schizophrenia; Weight Loss; Young Adult

Clozapine, while effective in treatment refractory schizophrenia, is associated with significant weight gain, heart disease and increased risk of type 2 diabetes mellitus (T2DM). Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation.. A 24-week double-blind placebo-controlled trial of concomitant prescription of metformin at clozapine commencement. Eighty-six people being commenced on clozapine will be randomised to placebo or metformin (variable dose, up to 2 g/day). The primary outcome is comparative end point body weight, between the placebo and metformin groups. Secondary outcomes are comparative rates of conversion to T2DM, alteration of metabolic syndrome parameters, proportion gaining >5% body weight and changes in diet and appetite. We will additionally examine biomarkers associated with change in weight among trial participants.. Ethics approval was granted by the Metro South Human Research Ethics Committee HREC/17/QPAH/538-SSA/17/QPAH/565. We plan to submit a manuscript of the results to a peer-reviewed journal, and present results at conferences, consumer forums and hospital grand rounds.. ACTRN12617001547336; Pre-results.

Topics: Antipsychotic Agents; Body Mass Index; Body Weight; Clozapine; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Male; Metabolic Syndrome; Metformin; Obesity; Research Design; Schizophrenia; Secondary Prevention; Treatment Outcome; Weight Gain; Weight Loss

Increased body weight and hyperlipidemia caused by antipsychotics may be associated with improved antipsychotic efficacy in schizophrenia. If this association has a causal interrelationship via a genuine pathophysiological mechanism, then body weight loss in antipsychotic-treated patients would be accompanied by worsened psychopathology. This could have clinical implications.. To explore whether the decreased body weight in these patients is associated with a worsened psychopathology.. In our previously published study, a 16 week treatment period with add-on orlistat (but not placebo) resulted in body weight loss in male (but not female) clozapine- or olanzapine-treated overweight or obese patients. In the current study, we investigated whether body weight loss in those male patients could worsen psychosis. Changes in the Positive and Negative Syndrome Scale (PANSS) scores within groups and body weight changes and lipid profiles over the treatment period were analysed by the paired samples t-test. Between-group comparisons were analysed by the independent samples t-test.. Over the treatment period body weight decreased by 2.56 ± 3.25 kg from initial 106.02 ± 12.61 kg (p = 0.04) for the orlistat group, with no statistically significant changes for the placebo group. Lipid levels did not change in either group. The orlistat-induced weight decrease was not associated with worsening in the PANSS scores.. Weight loss was not associated with a worsening of psychosis. The interrelationship between the antipsychotic-induced weigh gain and improved schizophrenia psychopathology observed in earlier studies appears to be indirect. Orlistat treatment in our study did not worsen psychopathology in this population.

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Female; Humans; Lactones; Lipid Metabolism; Male; Middle Aged; Obesity; Olanzapine; Orlistat; Psychiatric Status Rating Scales; Psychopathology; Schizophrenia; Weight Loss

Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Colon; Constipation; Cross-Sectional Studies; Diarrhea; Double-Blind Method; Finland; Humans; Incidence; Lactones; Laxatives; Obesity; Olanzapine; Orlistat; Overweight; Patient Dropouts; Prevalence; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Weight Loss

To explore long-term effects of orlistat in adult clozapine- or olanzapine-treated patients with DSM-IV-diagnosed schizophrenia and overweight or obesity who tolerate orlistat.. Orlistat or placebo was added to clozapine or olanzapine in stable doses in a 16-week randomized controlled trial. Open-label orlistat was added to the antipsychotics during a 16-week extension phase for those completing the double-blind phase. No low-calorie diet or participation in behavioral programs was required. Body weight (primary outcome) and some metabolic parameters were measured prospectively. Analyses were performed for those completing both phases (ie, population differing from that reported earlier). The study was conducted from 2004 through 2005.. During the open-label phase, the 44 patients experienced mean ± SD body weight loss of -1.29 ± 3.04 kg, P = .007. During both phases, men (but not women) showed a weight loss of -2.39 ± 5.45 kg, P = .023. Some subgroups showed desirable changes in several metabolic parameters. Prolonged (32 weeks) orlistat treatment yielded no additional benefits as compared to short (16 weeks) treatment.. In clozapine- or olanzapine-treated overweight or obese patients able to take orlistat on a long-term basis, the drug, with no concomitant hypocaloric diet or behavioral interventions, caused moderate weight loss only in men. However, some metabolic benefits may be achieved independently of weight changes. In patients who do not respond to orlistat within the first 16 weeks, continuation treatment may provide no additional benefits.. controlled-trials.com Identifier: ISRCTN65731856.

Topics: Adult; Anti-Obesity Agents; Antipyretics; Benzodiazepines; Cholesterol; Cholesterol, LDL; Clozapine; Double-Blind Method; Female; Humans; Lactones; Male; Obesity; Olanzapine; Orlistat; Schizophrenia; Sex Factors; Treatment Outcome; Weight Loss

Clozapine represents the treatment of choice for refractory psychosis, although a significant number of individuals demonstrate suboptimal response to it as well, leading to clozapine augmentation strategies. A variety of agents have been investigated in this regard, including mood stabilizers, such as anticonvulsants. Within this group of medications, topiramate is unique in that it is associated with weight loss, making it an attractive option because of clozapine's notable risk for associated metabolic disturbance. A 12-week naturalistic, open study was carried out to examine the potential benefits of topiramate in clozapine-treated individuals with schizophrenia demonstrating a suboptimal clinical response. We were specifically interested in clinical symptoms, changes in metabolic parameters, and tolerability. A total of 20 subjects were enrolled, and 16 completed the study, including 5 individuals with type 2 diabetes. Topiramate augmentation led to a 14% improvement in total Brief Psychiatric Rating Scale scores (P = 0.0003), a 2.5% decrease in body weight (P = 0.015), and was generally well tolerated, paraesthesia being the most common side effect. These findings support topiramate as a viable augmentation strategy in clozapine partial responders, with evidence of both clinical and metabolic benefits.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Schizophrenia; Topiramate; Treatment Outcome; Weight Loss

Antipsychotic medications are associated with weight gain and metabolic dysregulation, yet little is known about the management of obesity among individuals with severe and persistent mental illness. Thus we sought to evaluate the potential utility of a behavioral weight control program for this population.. Outpatients receiving psychiatric care at a university medical center who had a body mass index (BMI; weight in kg/[height in m](2)) >or= 30 and were currently taking antipsychotic medication participated in a 12-week group behavioral weight control program. A medical chart review was conducted for each participant's body weight over the 10 months prior to beginning the program. A multiple baseline design was used to determine the impact of the intervention on BMI through 12-month posttreatment follow-up. We also assessed self-reported eating behavior, physical activity, and health-related quality of life. Data were collected from October 2000 to July 2003.. Among 35 patients who began the program, 29 (83%) completed treatment, with mean (+/- SD) weight loss of 5.04 (+/- 7.52) pounds (p = .001) and improvements in eating, activity, and quality of life. At 3-month posttreatment follow-up (N = 27; 77%), total mean weight loss was 7.14 (+/- 11.47) pounds (p = .003). Results of a longitudinal model based on general estimating equations indicated that, relative to the pretreatment period, BMI decreased significantly during treatment and remained stable through 12-month posttreatment follow-up.. Behavioral weight control is a promising approach to the treatment of obesity among outpatients taking antipsychotic medications, but longer and more robust interventions are needed.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Behavior Therapy; Body Mass Index; Clozapine; Comorbidity; Feasibility Studies; Feeding Behavior; Female; Health Status; Humans; Male; Mental Disorders; Obesity; Quality of Life; Treatment Outcome; Weight Loss

Weight gain is a common side effect of clozapine treatment and may expose patients to obesity-associated health risks. We proposed that concomitant treatment with an appetite suppressant such as phenylpropanolamine (PPA) would lead to a decrease in appetite and therefore loss of weight.. This was a 12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on clozapine treatment for at least 4 months and had gained > 10% of their baseline body weight since starting clozapine. Patients were evaluated for adverse effects and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a short dietary quiz, and blood indices were completed monthly.. Sixteen patients were equally randomly assigned to receive PPA or placebo. The groups did not differ in mean age, baseline weight, dose of clozapine, baseline PANSS scores, or the percent of weight gained since the start of clozapine. There was no significant effect of treatment on weight (t = 0.219, df = 10, p = .831). There was no significant change in either the total PANSS scores (t = -0.755, df = 10, p = .468), the positive or negative symptom cluster scores, or any of the remaining variables.. Phenylpropanolamine 75 mg/day was well tolerated but was not effective in reversing established weight gain associated with clozapine treatment in stable outpatients with schizophrenia.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Appetite Depressants; Clozapine; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Obesity; Phenylpropanolamine; Pilot Projects; Placebos; Psychiatric Status Rating Scales; Research Design; Schizophrenia; Treatment Outcome; Weight Gain; Weight Loss

Dopamine (DA) neurons in the ventral tegmental area (VTA) modulate physical activity and feeding behaviors that are disrupted in obesity. Yet, the heterogeneity of VTA DA neurons has hindered determination of which ones might be leveraged to support weight loss. We hypothesized that increased activity in the subset of VTA DA neurons expressing neurotensin receptor-1 (NtsR1) might promote weight loss behaviors. To test this, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to activate VTA NtsR1 neurons in normal weight and diet-induced obese mice. Acute activation of VTA NtsR1 neurons (24hr) significantly decreased body weight in normal weight and obese mice by reducing food intake and increasing physical activity. Moreover, daily activation of VTA NtsR1 neurons in obese mice sustained weight loss over 7 days. Activating VTA NtsR1 neurons also suppressed how much mice worked to obtain sucrose rewards, even when there was high motivation to consume. However, VTA NtsR1 neural activation was not reinforcing, nor did it invoke liabilities associated with whole-body NtsR1 agonism such as anxiety, vasodepressor response or hypothermia. Activating VTA NtsR1 neurons therefore promotes dual behaviors that support weight loss without causing adverse effects, and is worth further exploration for managing obesity.

Topics: Animals; Clozapine; Dopaminergic Neurons; Mice; Obesity; Receptors, Neurotensin; Reward; Ventral Tegmental Area; Weight Loss

Even though effectiveness of clozapine on treatment resistant schizophrenia has been repeatedly demonstrated, it is also associated with many adverse effects including weight gain. Curiously, significant weight loss may occur in some patients. In this case report we discussed whether the observed weight loss could be a negative prognostic factor. The 56 year-old male patient, followed up with the diagnosis of schizophrenia for 20 years, had persistent positive and negative symptoms despite concurrent use of different antiypsychotics. He was diagnosed with treatment-resistant schizophrenia and started on clozapine with dose titration to 500 mg/day over 3 months. He was observed to have lost 17.6% of his initial body weight after 7 months of therapy. The Positive and Negative Syndrome Scale (PANSS) score of the patient did not change significantly. There are a few case reports in the literature on weight loss during clozapine therapy. Some proposed that the weight loss could be a sign of weak response to treatment which is based on the observation that the clinical response might be poor when there is a weight loss and no change in blood triglyceride levels is observed with the treatment. There is a need for more case-control and preclinical studies to explain the mechanisms underlying weight loss and weak response to clozapine therapy in schizophrenia.

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Schizophrenia; Treatment Outcome; Weight Loss

Clozapine is one of the second generation antipsychotics most commonly associated with serious metabolic side effects including weight gain. Unexpectedly, weight loss can also be seen as a rare side effect of clozapine. The mechanism underlying clozapine induced weight loss is not clearly understood. Several factors including certain brain areas, neurotransmitters, neuropeptides and genetic variants were identified to play a role in weight loss associated with clozapine. In some patients who were reported to have a significant weight loss (13.5-50% of body weight) with clozapine, weight loss might not be associated with any underlying physical disorder. Weight loss may be due to the patients' engagement in diet and exercise after clinical improvement, pharmacodynamic effects of clozapine, or other medical problems such as gastrointestinal tract hypomotility caused by clozapine. Some case reports suggested that clozapine-associated weight loss might be a sign of poor response to clozapine. Clinicians should keep in mind the fact that a specific group of patients may lose weight during clozapine treatment. In this case report, possible causes of weight loss due to clozapine use is discussed. We also discussed the possible relationship between clozapine dose and weight loss which has not drawn attention in previous case reports.

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Schizophrenia; Weight Loss

Topics: Adolescent; Antipsychotic Agents; Catatonia; Clozapine; Delusions; Feeding and Eating Disorders of Childhood; Haiti; Humans; Male; Marijuana Abuse; Olanzapine; Schizophrenia; Weight Loss

Topics: Antipsychotic Agents; Clozapine; Female; Humans; Mammaplasty; Middle Aged; Schizophrenia; Weight Loss

Topics: Adult; Clozapine; Diabetes Mellitus, Type 2; Exenatide; Humans; Male; Peptides; Schizophrenia; Venoms; Weight Loss

Dysphagia is listed as a 'rare' side effect following clozapine treatment. In this case report, we describe how significant clozapine-induced dysphagia has led to significant reduction of nutritional intake with subsequent substantial weight loss. An 18-year-old single man with an established diagnosis of treatment-resistant paranoid schizophrenia recovered well on a therapeutic dose of clozapine. However, he was noted to lose weight significantly (up to 20% of his original weight) as the dose was uptitrated. This was brought about by development of dysphagia, likely to be due to clozapine. Addition of nutritional supplementary liquids and initiation of a modified behavioural dietary/swallowing programme, while repeatedly mastering the Mendelsohn manoeuvre technique, alleviated the swallowing difficulties and restored his weight.

Topics: Adolescent; Antipsychotic Agents; Clozapine; Deglutition Disorders; Diagnosis, Differential; Humans; Male; Schizophrenia, Paranoid; Treatment Outcome; Weight Loss

People with severe mental illness have a 20-year life-expectancy shortfall. The majority of antipsychotic medications are associated with obesity and heightened diabetes risk. People with severe mental illness less frequently achieve benchmarked diabetes care, often attributed to poor adherence, lower clinical attendance and documented medical biases in treatment. This case is presented to highlight the profound effect medication change can have on diabetes control.. A 56-year-old man with a 42-year history of schizophrenia had required clozapine treatment for the preceding 14 years. Type 2 diabetes and obesity occurred within 4 years of clozapine instigation. Glycaemic control had been continuously poor, despite frequent contact with diabetes services and multiple medications, including insulin at a dose exceeding 200 IU daily. Request for consideration of antipsychotic review and close interaction with the psychiatry team was initiated at the diabetes outpatient clinic. A gradual medication switch from clozapine to aripiprazole was associated with a reduction in HbA(1c) from 80 to 50 mmol/mol (9.5 to 6.7%) over 4 months, associated with a weight loss of 10 kg. Over the ensuing 2 years, the improvement in HbA(1c) has endured, with total weight loss of 13 kg and halving of insulin requirements.. This case illustrates the benefits of engagement between endocrinologists and psychiatrists to achieve the shared goal of improved physical health in severe mental illness. Greater interdisciplinary collaboration will help bridge the life-expectancy gap in severe mental illness and may assist in preventing disabling diabetes complications in this vulnerable patient group.

Topics: Antipsychotic Agents; Aripiprazole; Blood Glucose; Clozapine; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Piperazines; Quinolones; Schizophrenia; Treatment Outcome; Weight Loss

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Liraglutide; Middle Aged; Obesity; Receptors, Glucagon; Schizophrenia; Weight Loss

Topics: Antipsychotic Agents; Body Weight; Clozapine; Humans; Male; Middle Aged; Schizophrenia; Weight Loss

Although weight gain is one of the most widely studied adverse effects of second-generation antipsychotics, only relatively few studies have specifically evaluated the long-term effect of switching antipsychotic medication on body weight. We aimed to evaluate the impact of switching antipsychotics on body mass index (BMI) during a 6-month follow-up period in a large cohort of patients with schizophrenia.. Data came from a 6-month prospective naturalistic survey in 6007 patients with schizophrenia.. We prospectively studied the effect on BMI of initiating or switching antipsychotic medication after 6 months of treatment among 3801 patients with schizophrenia in a real-life setting. Patients who were being treated with clozapine or olanzapine at baseline were more likely to experience a decrease in BMI during the follow-up period than the patients who were being treated with a conventional antipsychotic (odds ratio, 2.25 and 1.68, respectively). Patients treated with aripiprazole and, to a lesser extent, those treated with risperidone were more likely to experience a decrease in BMI during follow-up than patients treated with conventional antipsychotics (odds ratio, 2.96 and 2.06, respectively).. Our findings suggest that switching antipsychotics could be an effective strategy for reducing or preventing weight gain.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Body Weight; Clozapine; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Piperazines; Prospective Studies; Quinolones; Risperidone; Schizophrenia; Weight Loss

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Humans; Olanzapine; Schizophrenia; Weight Loss

The authors report the case of a 44-year-old man with a long history of chronic enduring schizophrenia who experienced dramatic weight loss after commencing treatment with clozapine, an antipsychotic medication characteristically associated with the greatest degree of weight gain among medical treatments for schizophrenia. He was obese with a body mass index (BMI) of 41.5 kg/m(2), but after commencing clozapine therapy he experienced an improvement in psychotic symptoms and 40% loss of his body weight attained through an altered diet and exercise regime, which resulted in him attaining a normal BMI of 24.8 kg/m(2).

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Schizophrenia; Weight Loss

Clozapine is associated with weight gain. We report three patients with substantial weight loss following treatment with clozapine. The weight loss observed in the three patients was 33, 18 and 14.4 kg with percentage loss of body weight of 49, 18 and 21 respectively. Two patients had diabetes mellitus. History, physical examination and extensive investigations in the three patients did not reveal any cause that could account for the weight loss.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Clozapine; Diabetes Complications; Female; Humans; Male; Schizophrenia; Weight Loss

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Humans; Piperazines; Schizophrenia; Thiazoles; Time Factors; Weight Loss

The ability of clozapine to induce weight gain in female rats was investigated in three studies with progressively lowered doses of clozapine. In an initial preliminary high dose study, clozapine at 6 and 12 mg/kg (i.p., b.i.d.) was found to induce weight loss. In a subsequent intermediate dose study, we obtained no evidence for clozapine-induced weight gain despite using identical procedures and doses of clozapine (1-4 mg/kg, i.p., b.i.d.) with which we have observed olanzapine-induced weight gain, hyperphagia, enhanced adiposity and metabolic changes [Cooper G, Pickavance L, Wilding J, Halford J, Goudie A (2005). A parametric analysis of olanzapine-induced weight gain in female rats. Psychopharmacology; 181: 80-89.]. Instead, clozapine induced weight loss without alteration in food intake and muscle mass or changes in levels of glucose, insulin, leptin and prolactin. However, these intermediate doses of clozapine enhanced visceral adiposity and elevated levels of adiponectin. In a final study, low doses of clozapine (0.25-0.5 mg/kg, i.p, b.i.d.) induced weight loss. These data demonstrate that clozapine-induced weight gain can be much more difficult to observe in female rats than olanzapine-induced weight gain. Moreover, these findings contrast with clinical findings with clozapine, which induces substantial weight gain in humans. Clozapine-induced enhanced adiposity appears to be easier to observe in rats than weight gain. These findings, along with other preclinical studies, suggest that enhanced adiposity can be observed in the absence of antipsychotic-induced weight gain and hyperphagia, possibly reflecting a direct drug effect on adipocyte function independent of drug-induced hyperphagia [e.g. Minet-Ringuet J, Even P, Valet P, Carpene C, Visentin V, Prevot D, Daviaud D, Quignard-Boulange A, Tome D, de Beaurepaire R (2007). Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Molecular Psychiatry; 12: 562-571.]. These and other findings which show that the results of studies of antipsychotic treatment in animals do not always mimic clinical findings have important implications for the use of animal models of antipsychotic-induced weight gain. With regard to weight gain the results obtained appear to depend critically on the experimental procedures used and the specific drugs studied. Thus such models are not without limitations. However, they do consistently demonstrate the ability of various ant

Topics: Adiponectin; Adiposity; Animals; Antipsychotic Agents; Behavior, Animal; Benzodiazepines; Body Mass Index; Body Weight; Clozapine; Dose-Response Relationship, Drug; Eating; Female; Hyperinsulinism; Hyperphagia; Models, Animal; Olanzapine; Rats; Rats, Wistar; Research Design; Sex Factors; Weight Gain; Weight Loss

Topics: Adult; Antipsychotic Agents; Body Weight; Chronic Disease; Clozapine; Fructose; Humans; Male; Neuroprotective Agents; Obesity; Schizophrenia, Paranoid; Topiramate; Weight Loss

Clozapine has an unusual profile of adverse effects; among them, gastrointestinal (GI) side effects are important management concerns. The charts of patients in a state hospital who received clozapine for at least 3 months were reviewed. We compared the pre- and post-clozapine weights and changes in frequency and intensity of use of drugs prescribed for gastrointestinal symptoms for each subject (n = 99). There were statistically significant increases in the use of antacids (p < 0.02) and both bulk and non-bulk laxatives (p < 0.05, p < 0.03). Seventy-three percent of patients gained weight, of whom 27% gained over 10% body weight. This study confirms clozapine's association with weight gain, constipation, and upper GI symptoms. The literature concerning weight gain, and the mechanisms underlying GI adverse effects were reviewed.

Topics: Adult; Antacids; Antipsychotic Agents; Body Weight; Cathartics; Clozapine; Constipation; Female; Histamine H2 Antagonists; Humans; Male; Middle Aged; Weight Gain; Weight Loss