Side Effects Of Atypical Antipsychotics Research Articles

Atypical Antipsychotics Rapidly and Inappropriately Switch Peripheral Fuel Utilization to Lipids, Impairing Metabolic Flexibility in Rodents

Patients taking atypical antipsychotics are frequented by serious metabolic (eg, hyperglycemia, obesity, and diabetes) and cardiac effects. Surprisingly, chronic treatment also appears to lower free fatty acids (FFAs). This finding is paradoxical because insulin resistance is typically associated with elevated not lower FFAs. How atypical antipsychotics bring about these converse changes in plasma glucose and FFAs is unknown. Chronic treatment with olanzapine, a prototypical, side effect prone atypical antipsychotic, lowered FFA in Sprague-Dawley rats. Olanzapine also lowered plasma FFA acutely, concomitantly impairing in vivo lipolysis and robustly elevating whole-body lipid oxidation. Increased lipid oxidation was evident from accelerated losses of triglycerides after food deprivation or lipid challenge, elevated FFA uptake into most peripheral tissues (∼2-fold) except heart, rises in long-chain 3-hydroxylated acyl-carnitines observed in diabetes, and rapid suppression of the respiratory exchange ratio (RER) during the dark cycle. Normal rises in RER following refeeding, a sign of metabolic flexibility, were severely blunted by olanzapine. Increased lipid oxidation in muscle could be explained by ∼50% lower concentrations of the negative cytoplasmic regulator of carnitine palmitoyltransferase I, malonyl-CoA. This was associated with loss of anapleurotic metabolites and citric acid cycle precursors of malonyl-CoA synthesis rather than adenosine monophosphate-activated kinase activation or direct ACC1/2 inhibition. The ability of antipsychotics to lower dark cycle RER in mice corresponded to their propensities to cause metabolic side effects. Our studies indicate that lipocentric mechanisms or altered intermediary metabolism could underlie the FFA lowering and hyperglycemia (Randle cycle) as well as some of the other side effects of atypical antipsychotics, thereby suggesting strategies for alleviating them.

Strategies to Close the "Mortality Gap"

Strategies to Close the "Mortality Gap"

Are Weight Gain and Metabolic Side Effects of Atypical Antipsychotics Dose Dependent?

Numerous publications have provided evidence for clinically important metabolic adverse effects of antipsychotics, but there is no systematic evaluation as to whether weight gain and other metabolic changes are dose dependent. This review of the available literature aimed to explore a possible relationship between dosage of second-generation antipsychotics (SGAs) and the degree of metabolic side effects. A literature review was conducted in 3 steps: (1) Articles published between 1975 and 2004 were identified on the basis of the bibliography of an extensive review of the metabolic effects of SGAs. (2) Articles published between 2004 and 2008 were identified by a PubMed search with the keywords weight gain, metabolic, glucose, insulin, and lipid AND dose combined with amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, and ziprasidone. (3) A hand search was conducted based on the bibliography of the identified articles. All studies that provided information on metabolic side-effects in different dose ranges were selected. Data extraction was carried out independently by 2 observers. Preliminary evidence suggests a dose-response relationship between clozapine and olanzapine serum concentrations and metabolic outcomes, although the association between administered daily dose and metabolic outcomes is not clear. Data are controversial with regard to risperidone, and no study has as yet assessed risperidone serum concentrations in association with metabolic outcomes. For the other SGAs, there was little evidence to suggest a dose-response relationship, although, in these agents also, no assessment of serum concentrations was conducted. The finding that metabolic complications may be associated with clozapine and olanzapine plasma concentrations provides further evidence for a causal contribution to the metabolic disturbances observed with these agents. Further well-designed, prospective studies investigating a possible association between SGA serum concentrations and metabolic outcomes are needed.

Effects of nutritional intervention on body weight and body composition of obese psychiatric patients taking olanzapine

Objective Weight gain is an established side effect of atypical antipsychotics in patients with severe mental illness (SMI). Previous studies have shown positive effects of nutritional interventions in weight loss. The purpose of this study was to investigate the effects of a nutritional intervention on the body weight and body composition of patients with SMI taking olanzapine in Greece. Methods Eighty-two patients with SMI treated with olanzapine (22 men, 60 women) and 58 healthy controls (12 men, 46 women) were followed for 3 mo. All patients with SMI were obese, with an average body mass index of 33.12 ± 0.74 kg/m 2 and body weight of 94.61 ± 2.50 kg. A nutritional program was designed for each participant based on anthropometric characteristics, health profile, and dietary needs. Pre- and postintervention anthropometric and body composition measurements were performed. Results Significant weight loss and fat loss were found in the healthy controls and patients with SMI from baseline to 3 mo ( P < 0.05). However, the patients with SMI had a less significant decrease in waist circumference ( P < 0.05) compared with healthy controls. The healthy male controls and male patients with SMI demonstrated greater decreases in body weight and waist circumference compared with female participants ( P < 0.05). Conclusion Patients with SMI appear to respond effectively to a nutritional program demonstrating significant decreases in body weight and body composition despite the use of olanzapine. Because gender differences may exist in weight loss, it is possible that gender should be taken into account for a more appropriate treatment of obesity in this population.

C.02.02 Options for addressing the side effects of atypical antipsychotics

Treatment options for patients with schizophrenia are more plentiful than ever before. Despite their established efficacy in treating schizophrenia symptoms, typical or first-generation compounds are associated with high rates of troubling extrapyramidal side effects. Moreover, there is still an unmet therapeutic need for the management of negative, cognitive and affective symptoms of schizophrenia. Second-generation antipsychotics were developed with the promise of enhanced efficacy and improved tolerability relative to their first-generation predecessors. The existing clinical trials, however, have not conclusively answered the questions about the clinical advantages and the cost-effectiveness of second-generation antipsychotics, especially from the perspective of clinical practice and public health. To address these issues, clinical trials of effectiveness have been conducted in the USA and the UK. Effectiveness trials are designed to answer the question ‘Will a treatment work in real-world conditions?’, whereas the existing industry-funded trials, often called efficacy trials, answer the question ‘Will a treatment work under ideal conditions?’. Overall, effectiveness trials have shown that second-generation antipsychotics are as effective and cause fewer extrapyramidal side effects relative to first-generation drugs, but come with new metabolic side effects. A clinical advantage over all other antipsy chotics was demonstrated for clozapine, the prototype of atypical antipsychotics. The goal for the next decade will be to use the current agents more intelligently, to match patients to drugs individually, and to continue the search for more efficacious antipsychotics and new add-on drugs for cognitive and negative symptoms.

EFFECTS OF SECOND GENERATION ANTIPSYCHOTICS ON LEPTIN AND GHRELIN

Abstract Background Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin. Method 112 patients who were treated either with clozapine ( n = 20), olanzapine ( n = 28), risperidone ( n = 22), quetiapine ( n = 20) or amisulpride ( n = 22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group ( n = 23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay. Results When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2 ± 6.7) and amisulpride group had the lowest mean value (3.7 ± 2.1) but still there was no statistically significant difference between six groups ( F = 1993, p = 0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups ( F = 11,473, p = 0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5 ± 86.8). Quetiapine treated group (378.1 ± 260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0 ± 150.0). Conclusion The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.

Effects of second generation antipsychotics on leptin and ghrelin

Background Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin. Method 112 patients who were treated either with clozapine ( n = 20), olanzapine ( n = 28), risperidone ( n = 22), quetiapine ( n = 20) or amisulpride ( n = 22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group ( n = 23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay. Results When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2 ± 6.7) and amisulpride group had the lowest mean value (3.7 ± 2.1) but still there was no statistically significant difference between six groups ( F = 1993, p = 0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups ( F = 11,473, p = 0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5 ± 86.8). Quetiapine treated group (378.1 ± 260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0 ± 150.0). Conclusion The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.

Metabolic side effects of atypical antipsychotics in early onset schizophrenia: One year follow-up pilot study

Metabolic side effects of atypical antipsychotics in early onset schizophrenia: One year follow-up pilot study

Side effects of atypical antipsychotics: a brief overview

This paper reviews the available evidence concerning the side effects of atypical antipsychotics, including weight gain, type II diabetes mellitus, hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects and cataract. Some recommendations about how to prevent and manage these side effects are also provided. It is concluded that atypical antipsychotics do not represent a homogeneous class, and that differences in side effects should be taken into account by clinicians when choosing an antipsychotic for an individual patient.

Essentials of Psychosomatic Medicine

Back to table of contents Previous article Next article Book ForumFull AccessEssentials of Psychosomatic MedicineCYNTHIA M.A. GEPPERT M.D., Ph.D., M.P.H.,CYNTHIA M.A. GEPPERT M.D., Ph.D., M.P.H.Search for more papers by this author,Published Online:1 Sep 2007https://doi.org/10.1176/appi.ajp.2007.07071140AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail The recognition of metabolic syndrome as an all too common side effect of atypical antipsychotics, the ever more certain and complex relationship of depression to coronary artery disease, and the increased importance of primary care as a major source of mental health referral all underscore the contemporary salience of psychosomatic medicine for all psychiatrists. This text is a condensed and updated version of the The American Psychiatric Textbook of Psychosomatic Medicine, also edited by Dr. Levenson, which is the official text of the recently (2003) recognized subspecialty of psychosomatic medicine. The author is one of the pioneers of modern consultation psychiatry and has carefully edited the work of many of the leading teachers and experts in American psychosomatic medicine. The book begins with a preface describing the history of the discipline formerly known as “consultation-liaison psychiatry” and a fine general chapter on psychiatric assessment and consultation in medical patients primarily in the hospital setting, which alone is worth the price of the book. Eighteen other chapters cover the major systems and medical specialties, including heart and lung disease, gastrointestinal, renal and endocrine disorders, oncology, rheumatology, chronic fatigue and fibromyalgia syndromes, infectious diseases and human immunodeficiency virus/acquired immune deficiency syndrome, dermatology, surgery, organ transplantation, neurology and neurosurgery, obstetrics, gynecology, and pediatrics, and two final chapters on physical medicine and rehabilitation and pain. The broad correspondence of the topics in Essentials of Psychosomatic Medicine to the larger book enables interested readers to supplement the excellent overviews provided with more detailed study in the Textbook of Psychosomatic Medicine. Noticeably absent and sorely missing from the parent volume are chapters on the near ubiquitous ethical and legal aspects of consultation psychiatry, which are among the most challenging tasks for trainees in the field. Similarly, a chapter on palliative care would seem requisite, as hospital psychiatrists must increasingly treat a sicker and older population.Each chapter truly meets the expectation of the biopsychosocial model of the psychosomatic pioneer Engel in that each covers epidemiology, diagnosis (including differential considerations), psychosocial factors influencing clinical presentation, and treatment encompassing both the psychological and pharmacological. Departing from the traditional psychiatrically-based organization of consultation-liaison textbooks, the medical disorder structure emphasizes how comorbid psychiatric and medical conditions interact, complicate, and amplify each other, requiring broad knowledge and wide competence in practitioners.The text is crisp and concise, with each chapter able to stand on its own as a reference for a specific patient-case or as a general review of a medical or surgical discipline. Citations and tables are clinically useful rather than the all too often exhaustive and exhausting. An attractive feature for continuing education is the inclusion of self-assessment questions and answers for each chapter. These user-friendly features make the present volume not only an outstanding study guide for psychosomatic subspecialty examinations, but also an excellent textbook for consultation-liaison clerkships and psychosomatic medicine fellowships.Something can be said to be “essential” in two allied senses: it can be necessary or indispensable or it can be basic and fundamental. This highly readable introduction to the cardinal dimensions of psychosomatic medicine fulfills both functions. The only real danger is that the title may mislead readers into thinking it is only a valuable volume for psychosomatic physicians when in actuality it is an excellent source for all psychiatrists and other mental health professionals seeking to hone their medical identity.Albuquerque, N.M.Book review accepted for publication July 2007 (doi:10.1176/appi.ajp.2007.07071140). FiguresReferencesCited byDetailsCited ByNone Volume 164Issue 9 September, 2007Pages 1442-1442THE AMERICAN JOURNAL OF PSYCHIATRY September 2007 Volume 164 Number 9 Metrics PDF download History Published online 1 September 2007 Published in print 1 September 2007

On the relationship of atypical and low-dose conventional antipsychotics with akathisia in a clinical patient population

Metabolic side-effects of atypical antipsychotics have led to concern about their relative safety compared with low doses of conventional neuroleptics. Akathisia is an often misdiagnosed side-effect, which leads to non-compliance and sometimes even exacerbation of psychosis or suicidal behaviour. In fact, little is known about the differences between antipsychotic drugs in clinical practice, since only as few as 20% of patients may be eligible for studies comparing antipsychotic medications with each other. The aim of this study was to find out if the use of conventional antipsychotics is associated with an increased risk of akathisia (compared with atypical antipsychotics) even when low doses of conventional antipsychotics are used. The Barnes Akathisia Rating Scale was used to evaluate akathisia in 100 outpatients on antipsychotic medication. Conventional antipsychotics were associated with an increased risk of akathisia compared with atypical antipsychotics, although the chlorpromazine equivalent doses of conventional antipsychotics were lower than those of the atypicals. An additional akathisia-provoking effect of SSRIs could not be ruled out. The results suggest favouring atypical antipsychotic medication in patients who may easily develop akathisia.

Physician Patterns of Metabolic Screening for Patients Taking Atypical Antipsychotics

The aim of this retrospective database study was to determine rates of screening for metabolic side effects by physician specialty in community hospital patients prescribed atypical antipsychotics. A pharmacy database review identified patients who were prescribed atypical antipsychotics over a 6-month period from July 1, 2004, to December 31, 2004. This list of patients was then cross-referenced with the laboratory database to determine if screening laboratory tests for metabolic abnormalities had been ordered. 13% of patients prescribed atypical antipsychotics had fasting blood glucose levels measured during the study period. 30% of patients prescribed atypical antipsychotics also had lipid panels measured during the study period. Screening rates varied by specialty of physician. Physicians trained in combined family practice and psychiatry had the highest rate of screening, followed by other nonpsychiatric specialties. Psychiatrists had the lowest rate of screening. The rate of screening for metabolic side effects of atypical antipsychotics in this community hospital setting was low.

Side Effects of Atypical Antipsychotics: Extrapyramidal Symptoms and the Metabolic Syndrome

In this article we examine the two major classes of side effects with atypical antipsychotics: extrapyramidal symptoms (EPS) and the metabolic syndrome (the triad of diabetes, dyslipidemia, and hypertension, with associated obesity). We conclude that atypical antipsychotics continue to have notable risks of EPS, particularly akathisia, and that these agents also appear to increase the risk of the metabolic syndrome, though this effect seems most marked with clozapine and olanzapine. Novel conclusions based on this review are as follows: we provide a classification scheme based on low versus high D2 binding affinity (which is, to our knowledge, a new means of classifying atypical antipsychotics); we emphasize that the akathisia risk is likely equal among agents and that tardive dyskinesia is an early, and not late, risk in treatment (a common misconception); we make the methodological point that in randomized clinical trials, there is a high risk of false-negatives regarding side effects; we raise the issue of confounding bias in epidemiological studies of metabolic syndrome; and we stress the need to compare side effects in the same studies and not different studies. Future prospective observational cohort studies must target side effects and be designed to collect and analyze data on confounding factors.

Risperidone-related Weight Gain

A serious side effect of atypical antipsychotics is increased body weight, which leads to further morbidity and nonadherence to medication. It has been suggested that both genetic and nongenetic variables may influence antipsychotics-related weight gain. This study aimed to simultaneously explore the effects of multiple candidate genes and environment factors on body weight of schizophrenia patients who received risperidone, a commonly used atypical antipsychotic agent. One hundred twenty-three ethnically Han Chinese inpatients with acutely exacerbated schizophrenia were given risperidone monotherapy for up to 42 days. Body weight and clinical manifestations were assessed biweekly. Drug efficacy was measured by the Positive and Negative Syndrome Scale (PANSS), and safety was evaluated by the Extrapyramidal Symptom Rating Scale (ESRS) and the UKU Side Effect Rating Scale. We collected body weight as the response value. Potential prognostic factors were baseline body weight, age, sex, diagnosis subtypes, risperidone dosage, PANSS total scores, treatment duration (weeks 0-6), and 15 genetic variants [across 10 candidate genes: 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, D1, D2, D3, and alpha1-adrenergic receptors, brain-derived neurotrophic factor (BDNF), and cytochrome P450 2D6 (CYP2D6)]. Because there were repeated assessments, multiple linear regression with the generalized estimating equation (GEE) method was used to adjust the within-subject dependence. Of 15 genetic polymorphisms examined, 5-HT2A 102-T/C, 5-HT2C -759-C/T, 5-HT6 267-C/T, BDNF 66-Val/Met, and CYP2D6 188-C/T significantly influenced body weight, and so did baseline body weight, age, gender, schizophrenia subtype, and treatment duration and efficacy. These results suggest that numerous genetic and nongenetic factors affect antipsychotics-related weight gain.

Antipsychotiques atypiques et dysfonction sexuelle : à propos de cinq cas associés à la rispéridone

Antipsychotiques atypiques et dysfonction sexuelle : à propos de cinq cas associés à la rispéridone

Metabolic side effects of atypical antipsychotics in children: a literature review

The objective of this review is to summarize the data about metabolic side effects of atypical antipsychotics in children. Original research articles about side effects of atypical antipsychotics used in children were reviewed. The data was obtained mainly through Medline searches, identifying articles focusing on the use of atypical antipsychotics in children. Forty studies that addressed the issue of metabolic side effects were selected. The use of atypical antipsychotics in children has been consistently associated with weight gain and moderate prolactin elevation, while only a few case reports address the issue of glucose dysregulation and dyslipidaemia. The risk of weight gain and hyperprolactinaemia might be higher in younger children. Other risk factors have also been associated with antipsychotic-induced metabolic disturbances. These changes seem to be reversible, at least in some cases. Metabolic side effects of atypical antipsychotics could lead to serious complications in children who are prescribed these medications. Serious considerations should be given before initiating treatment and consistent clinical monitoring is essential. More research is needed, especially regarding glucose dysregulation and dyslipidaemia.

Hormonal Correlates of Clozapine-Induced Weight Gain in Psychotic Children: An Exploratory Study

Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. Fasting serum samples for 24 patients with COS and 21 matched healthy controls (HC) were obtained. Levels of leptin, insulin, adiponectin, amylin, ghrelin, and tumor necrosis factor alpha were measured and compared between the groups. For 23 patients with COS, hormonal levels were measured at background and week 6 of clozapine treatment. Change in body mass index was correlated with levels of clozapine and changes in hormonal levels and clinical ratings. At baseline, COS did not differ significantly from HC on any hormonal measure. Clozapine treatment was associated with significant (7.9% +/- 8.5%) increase in mean body mass index. Only leptin levels increased significantly from baseline to week 6 on clozapine (p = .003). Body mass index increase was significantly correlated with decrease in ghrelin and adiponectin and was positively correlated with clinical improvement. This is the first study of weight gain-related hormones in children on clozapine. Hormonal changes are correlated with weight gain. How effectiveness of clozapine is linked to weight gain remains uncertain.

Side effects of atypical antipsychotics in the geriatric population

Geriatric patients are particularly sensitive to medication-related side effects, which also holds true for the antipsychotic drugs. Those of particular concern in the elderly include the anticholinergic side effects, which further impair cognitive function, parkinsonian events, orthostatic hypotension, cardiac disturbances, reduced bone mineral density, sedation, tardive dyskinesia, stroke, and cognitive slowing. It should also be noted that elderly patients have multiple medical problems such as cardiovascular disease, diabetes, dementia, and arthritis, and take multiple medications. The patients, their family members, and caregivers often have their own views on this issue. This article reviews some of these issues and addresses the side effects of the currently available atypical antipsychotic agents.

Side effects of atypical antipsychotics

Side effects of atypical antipsychotics

Recognizing and responding to atypical antipsychotic side effects.

Prescription of atypical antipsychotics to manage psychotic symptoms of dementia in the elderly has become a widespread practice, despite dementia being an off-label indication for use of these medications. Atypical antipsychotics are generally preferred over typical antipsychotics because they produce fewer extrapyramidal side effects, the Parkinson-like movement disorders caused by drugs that block dopamine receptor sites.