Metabolic adverse events in patients with mental illness treated with antipsychotics: a primary care perspective

Background: Individuals with mental illness are at a higher risk of medical mortality than the general population, primarily due to an increased risk of cardiovascular disease. There are a number of modifiable metabolic risk factors associated with some atypical antipsychotics that warrant careful monitoring and treatment in both psychiatric and primary care practice if the risk of cardiovascular disease is to be effectively reduced.Data Sources: Previous guidelines have focused on awareness of metabolic risk factors in psychiatry, yet few articles have appeared in the primary care-focused journals. We present pragmatic guidelines that focus on monitoring metabolic abnormalities in primary care based on established guidelines, including joint recommendations of the American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity, and the Mount Sinai conference.Data Synthesis: All patients receiving atypical antipsychotic agents associated with metabolic adverse events should be routinely monitored for weight gain and abnormalities in blood glucose and lipid levels. Effective communication and collaboration between mental health and primary care services and better access to primary care screening and treatment for individuals with mental health problems are needed.Conclusion: There is a clear need for awareness among primary care physicians, particularly as metabolic effects of atypical antipsychotics such as blood pressure and glucose and lipid levels are possibly best monitored in a primary care setting.     

Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC)

People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed in part to an increased risk of the modifiable coronary heart disease risk factors; obesity, smoking, diabetes, hypertension and dyslipidaemia. Antipsychotic medication and possibly other psychotropic medication like antidepressants can induce weight gain or worsen other metabolic cardiovascular risk factors. Patients may have limited access to general healthcare with less opportunity for cardiovascular risk screening and prevention than would be expected in a non-psychiatric population. The European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) published this statement with the aim of improving the care of patients suffering from severe mental illness. The intention is to initiate cooperation and shared care between the different healthcare professionals and to increase the awareness of psychiatrists and primary care physicians caring for patients with severe mental illness to screen and treat cardiovascular risk factors and diabetes.     

Physical health and schizophrenia

PURPOSE OF REVIEW: Patients with schizophrenia have higher than expected rates of morbidity and mortality. It is debatable whether this is related to shared risk factors, antipsychotic medication or inherent to the condition itself. This review will describe this association and the recent advances in the field. RECENT FINDINGS: The majority of patients with schizophrenia have at least one chronic comorbid medical condition. In the absence of systematic screening this may or may not be brought to the attention of health professionals. The cause of high rates of physical illness appears to be multifactorial involving shared vulnerability and genetic factors. Yet it is vascular risk factors and the adverse effects of prescribed medication that are most amenable to intervention. Current atypical antipsychotics may offer neurological and cognitive benefits, but there is accumulating evidence of problems with weight gain, diabetes, lipid dysregulation, metabolic syndrome and sexual side effects. SUMMARY: The physical health of patients with schizophrenia remains a concern. Yet the quality of medical and psychiatric care of patients with comorbid physical and mental health disorders has been shown to be unsatisfactory in several areas. We suggest that clinicians routinely assess and monitor physical health needs of patients with serious mental illness.     

Does colocated care improve access to cardiometabolic screening for patients with serious mental illness?

Objective

Individuals with serious mental illness (SMI; e.g., schizophrenia, bipolar disorder) experience disparities in mortality relative to the general population, mainly because of medical conditions (i.e., cardiometabolic disease).We assessed whether VA patients with SMI and receiving care from VA mental health facilities with colocated medical care were more likely to receive cardiometabolic risk assessments in accordance with clinical practice guidelines than patients from noncolocated facilities.

Methods

Patients with SMI identified prescribed second-generation antipsychotic medications in fiscal year (FY) 2007 receiving care from VA mental health facilities completing the VA Mental Health Program Survey were included. VA administrative data were ascertained to assess receipt of the following tests every 6 months in FY 2007: body mass index (BMI), blood pressure, lipid profile and fasting glucose.

Results

Out of 40,600 patients with SMI prescribed second-generation antipsychotics, 29% received all cardiometabolic tests (lipid, glucose, BMI and blood pressure). While 79% and 76% received blood pressure and BMI assessments, respectively, only 37% received a lipid test. Patients from colocated sites were more likely to receive all cardiometabolic tests (odds ratio=1.26, 95% confidence interval: 1.18–1.35, P<.001).

Conclusions

Colocated general medical providers in mental health clinics are more likely to provide cardiometabolic assessments for patients with SMI prescribed second-generation antipsychotics.     

Economic grand rounds: economic costs of failure to monitor adverse effects of second-generation antipsychotics: an underestimated factor

Since 2003, the U.S. Food and Drug Administration as well as the American Diabetes Association, the American Psychiatric Association, and others have called for routine monitoring of cardiometabolic risk factors for patients of all ages prescribed second-generation antipsychotic medications. This survey of major public and private mental health treatment systems in 2010 found that adherence to such guidelines was limited. The authors describe some of the impediments to widespread monitoring of cardiometabolic risk factors among psychiatric patients taking second-generation antipsychotics and advocate for a nationwide commitment to providing the organizational and financial supports necessary to ensure systematic screening of cardiometabolic health among such patients.     

The Metabolic Syndrome in Patients With Severe Mental Illnesses

BACKGROUND: Since the introduction of the first atypical antipsychotics in the early 1990s, this class of medication has been increasingly relied upon for the treatment of a variety of patients with psychotic and mood disorders.DATA SOURCES: The following retrospective review was derived from the MEDLINE database using the search terms metabolic syndrome, insulin resistance, obesity, diabetes, severe mental illness, schizophrenia, bipolar disorder, mood disorders, depression, unipolar depression, and prevalence from 1966 to the present. LITERATURE SYNTHESIS: Coincident with the growing usage of these agents, there have been a growing number of literature reports of changes in metabolic homeostasis among patients taking these medications. These changes have led to interest in evaluating whether there is a relationship among these mental illnesses, their psychiatric treatments, and certain physical comorbidities known collectively as the metabolic syndrome. This article reviews the existing literature around the metabolic syndrome in patients with severe mental illnesses. CONCLUSION: Patients with severe mental illnesses, particularly schizophrenia and chronic mood disorders, demonstrate a higher prevalence of metabolic syndrome or its components compared with the general population. Based upon this increased risk in these patients, baseline and periodic medical evaluations should become a standard component in ongoing clinical assessment.     

Treating Older Adults With Schizophrenia: Challenges and Opportunities

Schizophrenia affects people of all age groups. Treatment plans for older adults with schizophrenia must consider the effects of age on the course of the illness as well as on the response to antipsychotics and to psychosocial interventions. Positive symptoms of schizophrenia tend to become less severe, substance abuse becomes less common, and mental health functioning often improves. Hospitalizations are more likely to be due to physical problems rather than psychotic relapses. Physical comorbidity is a rule, however, and older age is a risk factor for most side effects of antipsychotics, including metabolic syndrome and movement disorders. We recently reported high rates of adverse events and medication discontinuation along with limited effectiveness of commonly used atypical antipsychotics in older adults. Psychosocial interventions such as cognitive behavioral social skills training are efficacious in improving functioning in older adults with schizophrenia. In formulating treatment plans for this population, a balanced approach combining cautious antipsychotic medication use with psychosocial interventions is recommended. Antipsychotic medications should generally be used in lower doses in older adults. Close monitoring for side effects and effectiveness of the medications and a watchful eye on their risk:benefit ratio are critical. In a minority of patients it may be possible to discontinue medications. Sustained remission of schizophrenia after decades of illness is not rare, especially in persons who receive appropriate treatment and psychosocial support—there can be light at the end of a long tunnel.Key words: schizophrenia, aging, antipsychotics, psychosocial treatments, cognition, psychosis     

Developing effective treatments for posttraumatic disorders among people with severe mental illness.

OBJECTIVE: The purpose of the study was to examine strategies for developing effective interventions for clients who have both serious mental illness and posttraumatic symptoms. METHODS: The authors conducted searches for articles published between 1970 and 2000, using MEDLINE, PsycLIT, and PILOTS. They assessed current practices, interviewed consumers and providers, and examined published and unpublished documents from consumer groups and state mental health authorities. RESULTS AND CONCLUSIONS: Exposure to trauma, particularly violent victimization, is endemic among clients with severe mental illness. Multiple psychiatric and behavioral problems are associated with trauma, but posttraumatic stress disorder (PTSD) is the most common and best-defined consequence of trauma. Mental health consumers and providers have expressed concerns about several trauma-related issues, including possible underdiagnosis of PTSD, misdiagnosis of other psychiatric disorders among trauma survivors, incidents of retraumatization in the mental health treatment system, and inadequate treatment for trauma-related disorders. Despite consensus that trauma and PTSD symptoms should be routinely evaluated, valid assessment techniques are not generally used by mental health care providers. PTSD is often untreated among clients with serious mental illness, or it is treated with untested interventions. It is important that policy makers, service system administrators, and providers recognize the prevalence and impact of trauma in the lives of people with severe mental illness. The development of effective treatments for this population requires a rational, orderly process, beginning with the testing of theoretically grounded interventions in controlled clinical trials.     

Metabolic considerations in the use of antipsychotic medications: a review of recent evidence

Compared with the general population, persons with schizophrenia have up to a 20% shorter lifespan, with cardiovascular disease as the leading cause of death. In addition, persons with schizophrenia have increased prevalence of the metabolic syndrome (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), increased prevalence of risk factors such as smoking, poverty, and poor nutrition, and reduced access to medical care. Results from the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) provide further evidence of the metabolic risk associated with different atypical antipsychotics. Based on this study and a growing number of other randomized clinical trials, clozapine and olanzapine treatment can produce substantial mean changes in weight and an increased risk of associated metabolic disturbances. Risperidone and quetiapine treatment can produce intermediate changes in mean weight in comparison to treatment with other atypical antipsychotics, with discrepant results with respect to metabolic risk. Aripiprazole and ziprasidone treatment induced the lowest mean changes in weight gain and had no effect on risk for adverse metabolic changes, among currently available atypical agents. Considerable evidence indicates that mentally ill patients often do not receive adequate recognition of, monitoring of, or care for their medical illnesses. There is a critical need for psychiatrists and primary care professionals to increase awareness of and attention to the physical health problems of persons with mental illness, including appropriate management of metabolic adverse events associated with psychiatric medications.     

Best practices: Optimizing care for people with serious mental illness and comorbid diabetes

Diabetes and obesity among patients with serious mental illness are common. Use of second-generation antipsychotics compounds risk, and widely prevalent unhealthy behaviors further contribute to negative outcomes. This column describes Targeted Training in Illness Management, a group-based psychosocial treatment that blends psychoeducation, problem identification, goal setting, and behavioral modeling and reinforcement. The intervention has been adapted to the primary care setting and is targeted at individuals with serious mental illness and diabetes. A key feature of the intervention is the use of peer educators with serious mental illness and diabetes to teach and model self-management. Promising results from a 16-week trial are reported.     

Racial disparities in the use of second-generation antipsychotics for the treatment of schizophrenia

OBJECTIVE: Despite recommendations that second-generation antipsychotics be used as first-line treatment for schizophrenia, previous studies have shown that blacks are less likely than whites to receive these newer drugs. This study determined the rate at which second-generation antipsychotics were prescribed to whites and blacks with schizophrenia who were treated as outpatients. METHODS: Data were collected from a community mental health clinic affiliated with an academic center in Rochester, New York. Multivariate logistic regression was used to examine the association between race and the receipt of a second-generation antipsychotic. RESULTS: Data were available for 456 patients: 276 whites and 180 blacks. Ninety-five percent received a second-generation antipsychotic. Whites were approximately six times more likely than blacks to receive a second-generation medication, after the analysis controlled for clinical and sociodemographic factors (p<.001). Most of this difference appeared to be driven by a disparity in the use of clozapine. CONCLUSIONS: In this sample, blacks were less likely than whites to receive second-generation antipsychotics, demonstrating a persistent gap in the quality of care for patients with schizophrenia.     

Responding to blood-borne infections among persons with severe mental illness

The Five-Site Health and Risk Study estimated prevalence rates of blood-borne infections, including the human immunodeficiency virus (HIV), hepatitis B, and hepatitis C, and addressed risk factors and correlates of infection among persons with severe mental illness. In this final article of the special section in this issue of Psychiatric Services, the authors review public health recommendations and best practices and discuss the implications of these results for community mental health care of clients with severe mental illness. Standard public health recommendations could be modified for use by community mental health providers. In addition, expansion of integrated dual disorders treatments and improving linkage with specialty medical care providers are recommended.     

HIV and people with serious mental illness: the public sector's role in reducing HIV risk and improving care.

OBJECTIVE: The paper discusses issues related to the detection, prevention of transmission, and treatment of human immunodeficiency virus (HIV) infection among persons with serious mental illness and suggests ways public mental health systems can address these issues. METHODS: MEDLINE was searched from 1980 through 1998, and all pertinent references were reviewed. RESULTS: Persons with severe mental illness are at greatly increased risk of HIV infection due to increased likelihood of high-risk sexual behaviors and injection drug use. The formidable barriers to detection and effective treatment of HIV that exist in this population can be attributed to the unique characteristics of this population, lack of knowledge and expertise among mental and physical health care providers, and fragmented mental and physical health care systems. CONCLUSIONS: In the last five years, treatments for HIV that are far more efficacious than earlier treatments have become available, making it more important for HIV infection be detected and treated among persons with serious mental illness. Public mental health systems need to implement active prevention policies and practices, educate both mental health and physical health care providers about key treatment issues, and develop effective linkages between mental and physical health care providers and systems.     

Strategies for the long-term treatment of schizophrenia: real-world lessons from the CATIE trial

Patients with schizophrenia have a chronic illness necessitating a biopsychosocial model of care that addresses the multiple dimensions of the disease, including coordinated primary care. Current research, including the lessons learned from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, shows that in addition to education, adherence, and minimizing adverse effects of psychopharmacologic agents, multimodal long-term treatment strategies are needed to address medical comorbidities, substance abuse, and both cognitive and social deficits. Health care professionals have the responsibility to monitor and help prevent adverse medical outcomes related to treatment with antipsychotics, in light of evidence that patients with schizophrenia are at risk for metabolic disorders and are undertreated for highly prevalent cardiovascular risk factors. These medical problems are particularly challenging in this population due to the chronicity of symptoms, cognitive limitations, social and financial challenges, and compliance issues with recommended medication treatment and therapeutic lifestyle changes. Mental health providers in the United States are now studying models that support the integration of psychiatric and nonpsychiatric medical treatment to address the complexity of multimodal schizophrenia care.     

Physical health monitoring of patients with schizophrenia

OBJECTIVE: Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings. METHOD: A consensus meeting including psychiatric and other medical experts assembled on October 17-18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis. Experts for each topic area formulated monitoring recommendations that were discussed by all of the participants until a consensus was reached. RESULTS: Consensus recommendations included regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction. Information from monitoring should guide the selection of antipsychotic agents. Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine. Patients who receive both first- and second-generation antipsychotic medications should be examined for extrapyramidal symptoms and tardive dyskinesia. Patients with schizophrenia should receive regular visual examinations. CONCLUSIONS: The conference participants recommended that mental health care providers perform physical health monitoring that typically occurs in primary care settings for their patients who do not receive physical health monitoring in those settings. This change in usual practice is recommended on the basis of the conference participants' belief that this additional monitoring will result in the earlier detection of common, serious risk factors that could, without detection and intervention, contribute to impaired health of patients with schizophrenia.     

Elderly patients with schizophrenia and depression: diagnosis and treatment

Background: The treatment of older patients with schizophrenia and depressive symptoms poses many challenges for clinicians. Current classifications of depressive symptoms in patients with schizophrenia include: Major Depressive Episodes that occur in patients with schizophrenia and are not classified as schizoaffective disorder, Schizoaffective Disorder, and Schizophrenia with subsyndromal depression in which depressive symptoms do not meet criteria for Major Depression. Research indicates that the presence of any of these depressive symptoms negatively impacts the lives of patients suffering from schizophrenia-spectrum disorders. Purpose: The purpose of this paper is to review the literature related to older patients with schizophrenia-spectrum disorders and co-occurring depressive symptoms, and to guide mental health professionals to better understand the diagnosis and treatment of depressive symptoms in patients with schizophrenia. Conclusions: The treatment of elderly patients with schizophrenia and depressive symptoms includes first reassessing the diagnosis to make sure symptoms are not due to a comorbid condition, metabolic problems or medications. If these are ruled out, pharmacological agents in combination with psychosocial interventions are important treatments for older patients with schizophrenia and depressive symptoms. A careful assessment of each patient is needed in order to determine which antipsychotic would be optimal for their care; second-generation antipsychotics are the most commonly used antipsychotics. Augmentation with an antidepressant medication can be helpful for the elderly patient with schizophrenia and depressive symptoms. More research with pharmacologic and psychosocial interventions is needed, however, to better understand how to treat this population of elderly patients.     

Ethnicity and prescription patterns for haloperidol, risperidone, and olanzapine

OBJECTIVE: Patients with schizophrenia may respond better to second-generation antipsychotics than to older antipsychotics because of their superior efficacy and safety profiles. However, the reduced likelihood among ethnic minority groups of receiving newer antipsychotics may be associated with reduced medication adherence and health service use, potentially contributing to poor response rates. This study examined whether ethnicity helped predict whether patients with schizophrenia were given a first- or a second-generation antipsychotic, haloperidol versus risperidone or olanzapine, and what type of second-generation antipsychotic was prescribed, risperidone or olanzapine, when other factors were controlled for. METHODS: Texas Medicaid claims were analyzed for persons aged 21 to 65 years with a diagnosis of schizophrenia or schizoaffective disorder who started treatment with olanzapine (N=1875), risperidone (N=982), or haloperidol (N= 726) between January 1, 1997 and August 31, 1998. The association between antipsychotic prescribing patterns among African Americans, Mexican Americans, and whites was assessed by using logistic regression analysis. Covariates included other patient demographic characteristics, region, comorbid mental health conditions, and medication and health care resource use in the 12 months before antipsychotic initiation. RESULTS: The results of the first- versus second-generation antipsychotic analysis indicated that African Americans were significantly less likely than whites to receive risperidone or olanzapine. Although not statistically significant, the odds ratio indicated that Mexican Americans were also less likely to receive risperidone or olanzapine. Ethnicity was not associated with significant differences in the prescribing patterns of risperidone versus olanzapine. CONCLUSIONS: When other factors were controlled for, African Americans were significantly less likely to receive the newer antipsychotics. Among those who received the newer antipsychotics, ethnicity did not affect medication choice.     

Patterns of emotional experience in schizophrenia: differences in emotional response to visual stimuli are associated with clinical presentation and functional outcome

Second generation antipsychotics (SGA) are associated with new onset diabetes, dyslipidemia and significant weight gain. Patients with schizophrenia are also at an increase risk of developing metabolic disorders, making routine metabolic monitoring important in patients with schizophrenia. The objective of our study was to identify glucose and lipid monitoring rates in Kansas Medicaid beneficiaries with schizophrenia who received long-term SGA therapy both before and after metabolic concerns of SGA had been introduced in the medical literature and after publication of metabolic monitoring guidelines from professional organizations in 2004. A retrospective cohort study was conducted using health care claims of Kansas Medicaid enrollees (age 18-64 years) with a diagnosis of schizophrenia and receiving long-term SGA. Proportions of these patients receiving annual blood glucose and serum lipid laboratory tests were calculated for two periods: 2002-2003 and 2005-2007. Bivariate and multivariate analyses were conducted to determine associations between demographic characteristics and monitoring outcomes. Among 2204 persons in the 2002 cohort, 23% received annual blood glucose monitoring and 10.1% received lipid monitoring. Among 1646 persons in the 2006 cohort, 75.3% received blood glucose monitoring and 52.5% received lipid monitoring. Our findings showed significant increases in blood glucose and lipid monitoring rates observed across a 4-year period in Kansas Medicaid enrollees with schizophrenia receiving SGA. The large rise in monitoring over time may be due to increase awareness of metabolic concerns by mental health care specialists, whom patients with schizophrenia are likely to receive their care from.