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Antipsychotics and Weigh Gain plus Diabetes
Comparisions of atypical and typical antipsychotics and their effect on weight gain and also articles on antipsychotics and diabetes are presented on this webpage. There appears to be hardly any research on dosage amounts as many bipolar people are prescribed lesser amounts of antipsychotics for their "cocktails" than do schizophrenics. Studies would be hard since many bipolars, including myself, take a variety of medication including antidepressants that can cause weight gain.
Another absence seems to be lack of studies researching if over a period of time, ones weight stabilizes.
Another problem not presented is that not all atypical antipsychotics work the same for at least this writer. For instance, Abilify might help for depression, and be less likely to cause weight gain but it doesn't take the place of Riserpdal for obsessive thought or rage.
Clozapine Brand name: Clozaril.
Risperidone Brand name Risperdal
Aripiprazole Brand Name Abilify
Ziprasidone Brand Name Geodon
Quetiapine Brand Name Seroquel
Olanzapine Brand Name Zyprexa

Schizophr Res. 2004 Sep 1;70(1):1-17. : The effects of antipsychotic therapy on serum lipids: a comprehensive review.
Meyer JM, Koro CE.
University of California, San Diego VAMC (MC 116A), 3350 La Jolla Village Drive, San Diego, CA 92161, USA.

Objectives: The purpose of this paper is to review the literature since 1970 documenting the effects of antipsychotic agents on serum lipids, including a discussion of possible mechanisms for the observed phenomena, the clinical significance and recommendations for monitoring hyperlipidemia during antipsychotic therapy. Results: High-potency conventional antipsychotics (e.g., haloperidol) and the atypical antipsychotics, ziprasidone, risperidone and aripiprazole, appear to be associated with lower risk of hyperlipidemia. Low-potency conventional antipsychotics (e.g., chlorpormazine, thioridazine) and the atypical antipsychotics, quetiapine, olanzapine and clozapine, are associated with higher risk of hyperlipidemia. Possible hypotheses for lipid dysregulation include weight gain, dietary changes and the development of glucose intolerance. Conclusions: Given the multiple cardiovascular risk factors seen in patients with schizophrenia, great care must be exercised in the choice of antipsychotic therapy to minimize the medical burden of additional risk imposed by hyperlipidemia. It is recommended that a lipid panel be obtained at baseline in all patients with schizophrenia, annually thereafter for patients on agents associated with lower risk of hyperlipidemia and quarterly in patients on agents associated with higher risk for hyperlipidemia. All patients with persistent dyslipidemia should be referred for lipid-lowering therapy or switched to a less lipid-offending antipsychotic agent.
Curr Drug Targets. 2004 Apr;5(3):279-99. : Drug induced weight gain, an impediment to successful pharmacotherapy: focus on antipsychotics.
Baptista T, Zarate J, Joober R, Colasante C, Beaulieu S, Paez X, Hernandez L.
Department of Physiology, P.O. Box 93, Los Andes University Medical School, Merida, 5101-A, Venezuela.
trinbap@yahoo.com

The antipsychotic drugs (APDs) are fundamental tools in current psychiatric practice. A new generation of agents, the atypical APDs, represents an important progress in the treatment of psychotic disorders. Unfortunately, some of them induce excessive body weight gain (BWG), obesity, hyperglycemia and dyslipidemia in the following order: clozapine approximately equal to olanzapine > quetiapine > risperidone > ziprasidone = aripiprazole. Appetite stimulation is probably the main mechanism of BWG and this is strongly correlated with the APD affinity for H1 (histaminergic) and alpha1 (adrenergic) receptors. A composed ratio of the APD affinity for diverse neurotransmitters involved in food intake (FI) regulation correlates with BWG as well. Endocrine/metabolic mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis, changes in insulin sensitivity (by conventional and atypical agents), hyperprolactinemia and gonadal dysfunction (by conventional APDs and risperidone) may also be involved. Importantly, patients with schizophrenia may have a genetically-based predisposition to appetite dysregulation, insulin resistance and endocrine imbalance involving gonadal steroids. Excessive BWG must be prevented or attenuated by proper drug selection, combining or switching agents, nutritional assistance and physical exercise. Amantadine. metformin and reboxetine proved to significantly lessen APD-induced BWG. Notwithstanding this, novel strategies are necessary to treat this side effect in a clinical population particularly prone to poor compliance and under a high risk of negative drug interaction.
J Clin Psychiatry. 2004 Apr;65(4):551-6. : Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia.
Lindenmayer JP, Czobor P, Volavka J, Lieberman JA, Citrome L, Sheitman B, McEvoy JP, Cooper TB, Chakos M.
Nathan Kline Institute, Orangeburg, N.Y. , USA.
lindenmayer@nki.rfmh.org

BACKGROUND: There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics. We are exploring whether this expanded clinical efficacy can also be seen in patients with treatment-resistant schizophrenia. METHOD: The subjects were 157 treatment-resistant inpatients diagnosed with DSM-IV schizophrenia or schizoaffective disorder. They were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol in a 14-week double-blind trial and rated with a standard measure of clinical antipsychotic efficacy (Positive and Negative Syndrome Scale [PANSS]). Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined. Data were gathered from June 1996 to December 1999. RESULTS: The underlying PANSS factor structure, as indicated by the factor loadings, was essentially identical at baseline and endpoint. At baseline, the excitement factor was followed by the positive, negative, cognitive, and depression/anxiety factors, explaining 49.4% of the total variance. At endpoint, the positive factor was followed by the negative, excitement, cognitive, and depression/anxiety factors, explaining 55.5% of the total variance. The endpoint data indicated statistically significant (p <.05) improvements over time on the positive factor for all 3 atypicals, but not for haloperidol. The negative factor showed significant improvement for clozapine and olanzapine, with significant worsening for haloperidol. Clozapine, olanzapine, and risperidone were superior to haloperidol on the negative factor, while clozapine was also superior to risperidone. The cognitive factor showed significant improvement for all atypicals, as did the depression/anxiety factor. Only clozapine showed improvement on the excitement factor and was superior to both haloperidol and risperidone. CONCLUSIONS: Treatment with atypical antipsychotics did not substantially change the underlying PANSS 5-factor structure. However, antipsychotic treatment with all 3 atypical medications was associated with significant improvements on 3 of 5 syndromal domains (positive, cognitive, and depression/anxiety) of schizophrenia. Clozapine and olanzapine also showed improvement on the negative factor. Only clozapine was associated with improvement on the excitement domain. This finding confirms that atypicals are associated with improvement of an expanded spectrum of symptoms in treatment-resistant patients.
World J Biol Psychiatry. 2004 Apr;5(2):73-82. : Atypical antipsychotics and diabetes mellitus.
Schwenkreis P, Assion HJ.
Department of Psychiatry and Psychotherapty, Ruhr-University of Bochum, Germany

Recently, increasing attention has been drawn to the potential diabetogenic effect of novel antipsychotics. Until now, large prospective studies examining the relationship between atypical antipsychotics and impaired glucose metabolism have been lacking. However, the case reports and retrospective studies that we review here suggest an increased risk of developing diabetes mellitus (DM) in patients treated with atypical antipsychotics compared to schizophrenic patients treated with conventional antipsychotics or those without treatment. Although most atypical antipsychotic agents might have a diabetogenic potential, the risk of developing DM might be higher in patients treated with either clozapine or olanzapine than with risperidone, whereas data on quetiapine and ziprasidone is presently limited and needs further attention. Possible mechanisms include the induction of peripheral insulin resistance and the direct influence on pancreatic beta-cell function by 5-HT1A/2A/2C receptor antagonism, by inhibitory effects via alpha 2-adrenergic receptors or by toxic effects. On the other hand, atypical antipsychotics might not be an independent risk factor for the development of DM, but hasten the onset of DM in patients bearing other risk factors. It is suggested that schizophrenic patients should be monitored for the occurrence of glucose metabolism abnormalities before starting atypical antipsychotics, and at a 3-month interval at least during therapy.
Pharmacotherapy. 2004 Feb;24(2):212-28. : Aripiprazole, a novel atypical antipsychotic drug.
Argo TR, Carnahan RM, Perry PJ.
College of Pharmacy, University of Iowa, Iowa City, Iowa 52242-1112, USA.

Before the 1990s, treatment of psychoses centered on conventional agents whose tolerability was limited by extrapyramidal side effects (EPS). The past decade has seen the emergence of a newer generation of antipsychotic agents, first with clozapine and followed shortly by risperidone, olanzapine, quetiapine, and ziprasidone. These agents have been touted as providing better negative symptom efficacy, less impaired cognition, and lower risk of extrapyramidal syndromes. However, evolving evidence suggests that several drugs in this class may be associated with significant weight gain and lipid abnormalities. Aripiprazole, a new atypical antipsychotic drug, displayed efficacy similar to that of haloperidol and risperidone and superior to that of placebo in numerous clinical trials. Aripiprazole does not cause significant prolactin elevation and is associated with a low rate of clinically significant weight gain compared with other atypical antipsychotics. Patients receiving aripiprazole experienced EPS at a rate similar to that seen with placebo. Aripiprazole provides a new treatment option with limited adverse effects for patients in need of antipsychotic therapy. : MedGenMed. 2004 Jan 20;6(1):5. : Rate of new-onset diabetes among patients treated with atypical or conventional antipsychotic medications for schizophrenia.
Ollendorf DA, Joyce AT, Rucker M.
Vice President, Analytic & Consulting Services, PharMetrics, Inc., Watertown, Massachusetts.

Abstract and Introduction Abstract Context: Understanding the association between use of antipsychotics and onset of diabetes. Objective: To compare the rates of new-onset diabetes mellitus (DM) between patients treated for schizophrenia with atypical or conventional antipsychotics. Design: Retrospective analysis of medical and pharmacy claims data. Setting: 61 US health plans. Patients: Patients with schizophrenia who were treated with atypical or conventional antipsychotics between September 1996 and June 2001 and were enrolled for 12 or more months before and 3 or more months after therapy initiation. Main Outcome Measures: New-onset DM was defined based on 2 or more claims with a diabetes diagnosis or initiation of antidiabetic therapy during follow-up. Rates of DM were compared between patients receiving atypical and conventional antipsychotics, and among 4 subgroups of patients receiving atypical antipsychotics (olanzapine, clozapine, risperidone, quetiapine). Statistical analyses employed logistic regression and Cox proportional hazards models. Results: Patients treated with atypical antipsychotics (N = 1826) were younger, had a lower rate of diagnosed hypertension, and longer duration of therapy than those receiving conventional antipsychotics (N = 617). The crude incidence of DM did not differ (2.46% vs 2.76% for atypical antipsychotics and conventional antipsychotics, P =.525). In Cox proportional hazards models, patients treated with atypical antipsychotics had a statistically significant, moderately increased risk of DM relative to conventional antipsychotics (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.06, 1.30); no significant differences in risk were observed when atypical antipsychotic cohorts were compared. In logistic regression models, no significant differences in DM risk were observed. Conclusions: Patients with schizophrenia treated with atypical antipsychotics had a moderately increased risk of DM relative to those treated with conventional antipsychotics, as measured by Cox proportional hazards models; such risk was not significantly different among patients treated with individual atypical medications.
Drugs. 2004;64(7):701-23. : Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications.
Melkersson K, Dahl ML.
Psychiatric Polyclinic, Sollentuna Hospital, Nytorpsvagen 10-12, SE-191 35 Sollentuna, Sweden.
Kristina.Melkersson@cns.ki.se

Adverse metabolic effects, such as diabetes mellitus, lipid abnormalities and weight gain, have increasingly been recognised with the use of the newer, so-called atypical antipsychotic drugs. This article reviews the current literature in the field and attempts to answer the question of whether the atypical antipsychotics differ in their effects on glucose-insulin homeostasis and lipid metabolism. It also addresses how then to manage the use of the atypical antipsychotics that do interfere with these metabolic systems. Differences in effects of atypical antipsychotics on leptin levels are also summarised and put into context; bodyweight gain associated with atypical antipsychotics is reviewed elsewhere.In summary, there are no large controlled trials published quantifying the prevalence of adverse effects on glucose-insulin homeostasis and lipid metabolism in patients receiving atypical antipsychotics. Nevertheless, the published articles and case reports reviewed in this article give a fairly good view of those adverse effects occurring with clozapine, olanzapine and risperidone, whereas little data are available regarding quetiapine, ziprasidone and zotepine, and no data exist for amisulpride and aripiprazole. Estimated rankings of the atypical agents, based on the available literature, show that the relative risk of glucose intolerance/diabetes mellitus, hyperlipidaemia and hyperleptinaemia is highest for clozapine and olanzapine, moderately high for quetiapine, rather low for risperidone and lowest for ziprasidone. Since adverse metabolic effects of atypical antipsychotics may have a negative influence on both the antipsychotic treatment outcome as well as the physical health of the patient, these effects have to be recognised and adequately managed. In this review, recommendations for prevention and treatment of the adverse metabolic effects are outlined.
J Am Med Dir Assoc. 2004 Jan-Feb;5(1):38-46. : Comment in: J Am Med Dir Assoc. 2004 Jan-Feb;5(1):57-8.
Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a geriatric population in the United States.
Feldman PD, Hay LK, Deberdt W, Kennedy JS, Hutchins DS, Hay DP, Hardy TA, Hoffmann VP, Hornbuckle K, Breier A.
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
pdfeldman@lilly.com

OBJECTIVES: The objective of this study was to investigate risk of diabetes among elderly patients during treatment with antipsychotic medications. DESIGN: We conducted a longitudinal, retrospective study assessing the incidence of new prescription claims for antihyperglycemic agents during antipsychotic therapy. SETTING: Prescription claims from the AdvancePCS claim database were followed for 6 to 9 months. PARTICIPANTS: Study participants consisted of patients in the United States aged 60+ and receiving antipsychotic monotherapy. The following cohorts were studied: an elderly reference population (no antipsychotics: n = 1,836,799), those receiving haloperidol (n = 6481) or thioridazine (n = 1658); all patients receiving any conventional antipsychotic monotherapy (n = 11,546), clozapine (n = 117), olanzapine (n = 5382), quetiapine (n = 1664), and risperidone (n = 12,244), and all patients receiving any atypical antipsychotic monotherapy (n = 19,407). MEASUREMENTS: We used Cox proportional hazards regression to determine the risk ratio of diabetes for antipsychotic cohorts relative to the reference population. Covariates included sex and exposure duration. RESULTS: New antihyperglycemic prescription rates were higher in each antipsychotic cohort than in the reference population. Overall rates were no different between atypical and conventional antipsychotic cohorts. Among individual antipsychotic cohorts, rates were highest among patients treated with thioridazine (95% confidence interval [CI], 3.1- 5.7), lowest with quetiapine (95% CI, 1.3-2.9), and intermediate with haloperidol, olanzapine, and risperidone. Among atypical cohorts, only risperidone users had a significantly higher risk (95% CI, 1.05-1.60; P = 0.016) than for haloperidol. Conclusions about clozapine were hampered by the low number of patients. CONCLUSION: These data suggest that diabetes risk is elevated among elderly patients receiving antipsychotic treatment. However, causality remains to be demonstrated. As a group, the risk for atypical antipsychotic users was not significantly different than for users of conventional antipsychotics.
J Clin Psychiatry. 2004;65 Suppl 6:20-9. : Treatment challenges and safety considerations for antipsychotic use in children and adolescents with psychoses.
McConville BJ, Sorter MT.
Department of Psychiatry, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0559, USA.
mcconvbj@email.uc.edu

With increased prescribing of psychotropic medications to children and adolescents, more attention should be given to the safety and tolerability of these drugs in this population. Compared with adults, children are especially vulnerable to adverse effects, including extrapyramidal symptoms (EPS), sedation, weight gain, and prolactin elevation. The prevalence of EPS is much higher in children treated with conventional antipsychotics than in those given atypical antipsychotics. Sedation, which can be minimized through gradual dose escalation, is common with risperidone, olanzapine, quetiapine, and ziprasidone. The relative propensities for producing weight gain in children and adolescents are olanzapine > risperidone > quetiapine. All conventional and some atypical antipsychotics (e.g., risperidone) increase serum prolactin levels. Nonetheless, preclinical studies suggest that atypical antipsychotics may have neuroprotective effects in the central nervous system; further studies, especially in children and adolescents, are required to confirm these results.
Paediatr Drugs. 2004;6(1):33-44. : Weight gain associated with atypical antipsychotic use in children and adolescents: prevalence, clinical relevance, and management.
Stigler KA, Potenza MN, Posey DJ, McDougle CJ.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

Atypical antipsychotics are increasingly prescribed to children and adolescents with neuropsychiatric disorders. Although their profile of potent antagonism at specific serotonin and dopamine receptors offers certain advantages compared with typical antipsychotics, their use has been associated with various adverse effects, including significant weight gain. This adverse effect is of particular concern in children and adolescents, secondary to the immediate and long-term health risks associated with weight gain, including obesity, diabetes mellitus, and hyperlipidemia. Indeed, from 1963 to 1991, the prevalence of obesity has approximately doubled in youth. Prior to selecting an atypical antipsychotic, a detailed review of the predictors of weight gain is necessary for every child and adolescent. Published data suggest that clozapine and olanzapine are associated with considerable weight gain, whereas risperidone and quetiapine have a moderate risk. Alternatively, ziprasidone and aripiprazole may exhibit a low risk for this adverse effect. Whereas behavioral and pharmacologic measures are available to manage weight gain associated with atypical antipsychotics, research is needed to establish more effective and safe interventions for this adverse effect in children and adolescents
Pharmacopsychiatry. 2004 Jan;37(1):1-11. : Atypical antipsychotics and new onset diabetes mellitus. An overview of the literature.
Cohen D.
dcohen@rijngeestgroep.nl

During the last few years, several case reports and studies have been published on the potential diabetes mellitus (DM)-inducing effect of some atypical antipsychotics, especially clozapine and olanzapine. The purpose of our study was to evaluate diabetogenic effects of atypical antipsychotics in the literature. In order to give a full-scale overview, both peer-reviewed publications and oral and poster presentations on this subject were screened. We found 27 case reports of new-onset DM for clozapine, 39 for olanzapine, 4 for risperidone, and 3 for quetiapine. Related to the year of introduction of these drugs on the market and the number of treatment days of each drug during the last 6 years in 13 western countries, Brazil, and Japan, the cases show an over-representation of cases related to olanzapine and clozapine. In the majority of cases, risk factors (DM family history, obesity, Negroid ethnicity) were present. Eighty-four percent of the cases arose in patients < 50 years, in contrast to the general population (most cases, > 50 years). Comparative epidemiological studies point in the same direction, with two studies showing no differences between the atypical drugs. Antipsychotic agents are used often for treatment of schizophrenia, a condition that appears to be associated with DM also in untreated subjects. Some antipsychotics appear to induce new-onset diabetes mellitus. In view of the health risks of DM and the predisposition in patients with schizophrenia, it is advised to be cautious with prescription of antipsychotics that are associated with new-onset DM. Especially in predisposed patients (family history of DM, obese, Negroid ethnicity), reticence in this respect is required. Moreover, careful monitoring of weight, BMI, and glucose levels is advised both before these antipsychotics are prescribed and during treatment.
Ann Pharmacother. 2003 Dec;37(12):1849-57. : Relationship of atypical antipsychotics with development of diabetes mellitus.
Citrome LL, Jaffe AB.
New York University School of Medicine, New York, NY and Clinical Research and Evaluation Facility, Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
citrome@nki.rfmh.org

OBJECTIVE: To review the pharmacoepidemiologic evidence for the link between exposure to atypical antipsychotics and the development of diabetes mellitus.DATA SOURCES: A MEDLINE search (1990-March 2003) was conducted.STUDY SELECTION AND DATA EXTRACTION: The search was limited to articles that described findings from analyses of large databases and used the words diabetes or hyperglycemia, and antipsychotic or clozapine or olanzapine or risperidone or quetiapine or ziprasidone or aripiprazole in the title or abstract. The odds ratio or relative risk, together with their corresponding confidence interval, was extracted.DATA SYNTHESIS: Results are conflicting, and this variability may be due to the different populations studied, different study designs, and the possibility of publication bias related to funding by the pharmaceutical industry. Nevertheless, an increased risk for diabetes mellitus appears to be present for patients receiving atypical antipsychotics. However, differential risk among the atypical antipsychotics is difficult to ascertain.CONCLUSIONS: Clinicians are urged to manage risk by regularly monitoring all patients receiving atypical antipsychotics for the emergence of diabetes mellitus. Future studies should carefully control for confounding variables such as age, diagnosis, change in weight, activity level, family history, and ethnicity.
CNS Spectr. 2003 Nov;8(11 Suppl 2):23-5. : Factors in antipsychotic drug selection: tolerability considerations.
Nasrallah HA.
University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

With the widespread use of atypical antipsychotics over the past several years, adverse metabolic effects have emerged as the most serious medical consequences of pharmacotherapy with some of these agents. Initially, weight gain and obesity were observed (especially with clozapine and olanzapine), but subsequently, type 2 diabetes and dyslipidemia became apparent as well. Further, many reports suggest that sudden and severe (occasionally fatal) diabetes ketoacidosis (DKA) can emerge during treatment with some atypical antipsychotics, even in the absence of adiposity. A marked increase of serum lipids (especially triglycerides) has also been reported, to varying degrees, with different atypicals. This article reviews the data regarding metabolic dysfunction in patients with psychosis (schizophrenia and bipolar disorder). Populations with psychosis have a 2-3-fold higher prevalence of diabetes even before treatment with any antipsychotics, suggesting a possible genetic linkage or comorbidity; this was confirmed with glucose regulation studies in schizophrenia and mania. The induction of type 2 diabetes with atypicals has further increased the prevalence of noninsulin-dependent diabetes from about 6% to 8% to 11% to 15% according to recent studies, and even higher rates of subclinical hyperglycemia. Serious weight gain (eg, 26-29 lbs after 1 year of clozapine or olanzapine treatment) is an important risk factor, but sudden DKA has now been reported in patients with minimal weight gain, suggesting alternative mechanisms, such as insulin resistance, as a direct effect of some atypicals. Psychiatrists can reduce the risk of metabolic disorders in schizophrenia and bipolar disorder by avoiding the use of certain atypicals as first-line treatment in patients with a personal or family history of diabetes, obesity, and hyperlipidemias. Regulatory agencies in some countries have already taken action in this regard.
Presse Med. 2003 Oct 18;32(34):1612-7. : [Antipsychotic drugs. Risk factors for diabetes]
[Article in French]
Stip E, Tranulis C, Legare N, Poulin MJ.
Centre de recherche Fernand-Seguin, Montreal, (Qc).
emmanuel.stip@umontreal.ca

ANTIPSYCHOTICS AND DIABETES: After 50 years' use of antipsychotics, it is pertinent to draw-up a circumspect review of the side effects of these psychotropic agents. Moreover, few articles have attempted to elucidate the relationship between the monitoring of carbohydrate metabolism and the prescription of this type of medication. SEVERAL MECHANISMS AT THE ORIGIN OF AN IMBALANCE IN GLYCAEMIA: Antipsychotics, notably the atypical forms, represent an additional factor of risk for developing diabetes. The weight gain secondary to this treatment plays an important part in this imbalance, but other mechanisms may also contribute. DEPENDING ON THE TYPE OF ANTIPSYCHOTIC: Our present knowledge is insufficient to be able to quantify the effect of each atypical antipsychotic on diabetes. The only tendency that has been reproduced in several studies concerns the increased risk associated with dibenzodiazepine antipsychotics (clozapine and olanzapine), compared with the other antipsychotics.
Ann Pharmacother. 2003 Oct;37(10):1381-6. : Weight change after an atypical antipsychotic switch.
Ried LD, Renner BT, Bengtson MA, Wilcox BM, Acholonu WW Jr.
College of Pharmacy, University of Florida, Gainesville, FL, USA.
ried@cop.ufl.edu

BACKGROUND: Atypical antipsychotics successfully treat schizophrenia and other conditions, with a lower incidence of extrapyramidal side effects than other agents used in treatment of these disorders. However, some atypical antipsychotics are associated with weight gain. OBJECTIVE: To quantify the impact on weight and identify atypical antipsychotics causing the least amount of weight gain among patients switched from risperidone to olanzapine and olanzapine to risperidone. METHODS: Patients included in the study (n = 86) were > or =18 years and had received > or =2 prescriptions for risperidone or olanzapine for > or =60 days, switched to the other atypical antipsychotic, and were dispensed > or =2 prescriptions for at least 60 days after the index date. Age, weight, and body mass index (BMI) were retrospectively abstracted from automated databases containing patient-specific prescription and vital sign information. RESULTS: At the time of their switch, the average patient age was 53.2 years (range 25-83). The average weight change in patients switched to olanzapine (n = 47) was +2.3 kg (p = 0.01) and the BMI change was +0.8 kg/m(2) (p = 0.02). The average percent body weight change was +2.8% and the BMI change was +3.0%. The average weight change after patients switched to risperidone (n = 39) was -0.45 kg (p = 0.69) and BMI change was -0.2 kg/m2 (p = 0.64). The average percentage weight change was -0.4% and BMI change was -0.5%. CONCLUSIONS: Practitioners' concern regarding weight changes after switching atypical antipsychotics seems warranted and patients should be provided consistent, ongoing weight monitoring. Further investigations should examine whether weight changes associated with atypical antipsychotic treatment further jeopardize this already at-risk population for severe comorbid conditions such as hypertension, coronary artery disease, and type 2 diabetes.
J Clin Psychopharmacol. 2003 Jun;23(3 Suppl 1):S21-6. : The implications of weight changes with antipsychotic treatment.
Sussman N.
Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA.
sussman01@popmail.med.nyu.edu

Patients receiving treatment with atypical antipsychotics commonly experience weight gain, which can cause considerable distress and can have deleterious effects on cardiovascular health. Because of the associated weight gain and potential direct effects on glucose metabolism, atypical antipsychotics have also been linked to the development of type II diabetes mellitus. Data on long-term treatment with these agents show that clozapine and olanzapine, followed by risperidone, were associated with the greatest degree of weight gain. A large body of data suggests that during long-term treatment, patients receiving the atypical antipsychotic quetiapine experience minimal weight gain. Data also suggest that quetiapine treatment does not increase the risk of developing type II diabetes. The use of atypical antipsychotics is increasing, as these agents are being prescribed for schizophrenia in lieu of conventional antipsychotics. Furthermore, these drugs have efficacy for treating other conditions such as bipolar disorder. Physicians prescribing atypical antipsychotics must be aware of the risk of weight gain and its associated comorbidities.
J Clin Psychiatry. 2003 May;64(5):598-604. : Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics.
Atmaca M, Kuloglu M, Tezcan E, Ustundag B.
Department of Psychiatry, School of Medicine, Firat University, Elazig, Turkey.
matmaca_p@yahoo.com

BACKGROUND: Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain. METHOD: The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002. RESULTS: Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups. CONCLUSION: Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine


Clin Ther. 2003 Apr;25(4):1150-71. : Differential effects of antipsychotic agents on the risk of development of type 2 diabetes mellitus in patients with mood disorders.
Gianfrancesco F, Grogg A, Mahmoud R, Wang RH, Meletiche D.
HECON Associates, Inc., Montgomery Village, Maryland 20886, USA.
fgianf1708@aol.com

BACKGROUND: Atypical antipsychotics are being used increasingly in the management of mood disorders. OBJECTIVE: The objective of this study was to investigate the association between exposure to antipsychotic therapy and newly reported type 2 diabetes mellitus in patients with mood disorders. METHODS: Claims data for the period January 1996 through December 1997 were analyzed for patients with mood disorders in 2 large US health plans. Logistic regression models were used to determine the odds of reporting diabetes in patients exposed to risperidone, olanzapine, or high- or low-potency conventional antipsychotics compared with untreated patients, taking into account duration of treatment and dosage. Some of the covariates used in the models were concurrent use of antipsychotics, use of other psychotropic drugs, age, sex, and length of observation. RESULTS: Based on the claims data, 849 patients were exposed to risperidone, 656 to olanzapine, 785 to high-potency conventional antipsychotics, and 302 to low-potency conventional antipsychotics; 2644 patients were untreated. The odds of newly reported type 2 diabetes in patients who received risperidone were not significantly different from those in untreated patients (12-month odds ratio [OR] = 1.024; 95% CI, 0.351-3.015). The odds in patients treated with high-potency conventional antipsychotics also did not differ significantly from those of untreated patients (12-month OR = 1.945; 95% CI, 0.794-4.786). Unlike patients who received risperidone or high-potency conventional antipsychotics, patients who received olanzapine (12-month OR = 4.289; 95% CI, 2.102-8.827) and low-potency conventional antipsychotics (12-month OR = 4.972; 95% CI, 1.967-12.612) had significantly higher odds for the development of type 2 diabetes compared with untreated patients. CONCLUSIONS: These findings suggest that some antipsychotics may increase the risk for the development of type 2 diabetes in patients with mood disorders and that the effect may vary by drug. In contrast to olanzapine and low-potency conventional antipsychotics, risperidone and high-potency conventional antipsychotics were not associated with an increased risk for development of type 2 diabetes in this patient population