Alex J  Mitchell  www.psycho-oncology.info University of Leicester (UK) Acknowledgements Davy Vancampfort, Belgium Marc De...
I. Background
What are Severe Mental Health problems? <ul><li>These usually include </li></ul><ul><li>Schizophrenia and related disorder...
Is there Accelerated mortality in SMI? <ul><li>Yes, there is premature mortality by 20 years on average </li></ul><ul><li>...
Schizophrenia –Standardized Mortality Ratio Pooled estimate=2.50  (95% CI=2.18-2.83) > > > > Saha Arch Gen Psychiatry. 200...
Mortality trends in Stockholm County  1976–79 to 1990–95, cardiovascular causes of death *Controlling for age at first dia...
Cardiovascular disease is primary cause of death in persons with mental illness* *Average data from 1996–2000 Data From  C...
What is the Concern Re Obesity in the Popn? <ul><li>In 1950 </li></ul><ul><li>25% US adults were overweight (BMI > 25) </l...
 
 
Obesity increases the risk of disease Willet et al. Guidelines for Healthy Weight (1999) NEJM 341, 427 - 433
Which Risk Factors Are Important? <ul><li>For cardiovascular disease and general mortality… </li></ul><ul><li>Blood pressu...
Ranking of selected risk factors: 6 leading causes of death by income group, estimates for 2004  Percentage of total (tota...
The following are important for diabetes IFG BP Waist HDL TG <ul><ul><li>≥  102 cm or 40 inches (m) </li></ul></ul><ul><ul...
How Many Antipsychotics are prescribed? <ul><li>About 6million prescriptions in the UK per year </li></ul><ul><li>Perhaps ...
Source: IMS;  Robert Rosenheck MD Global Antipsychotic Market Sales (MAT Q1 by Yr)
Most common uses of atypical antipsychotics Off label use accounts for  ~ 1/3 of prescriptions
 
II. Weight, diabetes complications of Atypicals     The following are of high concern in SMI  (next slide)
IFG BP Waist HDL TG <ul><ul><li>≥  102 cm or 40 inches (m) </li></ul></ul><ul><ul><li>≥  88 cm or 36 inches(f) </li></ul><...
Prevalence of diabetes in schizophrenia compared to general population 8.6% diabetes; n=415 Slide thanks to De Hert et al ...
Bipolar comparison study  – prevalence of metabolic disturbances van Winkel et al 2008 72.3 59.8 71.6 17.0 29.3 22.1 10.7 ...
BMI change after 52 weeks of olanzapine in bipolar patients Image Credit: Hennen (2004)
Antipsychotic-induced diabetes mellitus..warning in 2003 <ul><li>October 20, 2003 </li></ul><ul><li>FDA warns diabetes and...
About the CATIE Study of Atypicals….. <ul><li>•  Non-industry sponsored.  </li></ul><ul><li>•  1493 patients. </li></ul><u...
Comparison of Metabolic Syndrome and Individual Criterion Prevalence:  Fasting CATIE vs Matched NHANES III Subjects CATIE ...
CATIE: rates of pharmacological interventions for abnormal blood pressure, lipids and glucose Nasrallah et al   2006 n=148...
But not everyone gains weight….
20% do not gain weight over 2yrs of Olanzapine Treatment Data from Basson, Kinon JCP
Weight gain begins early, typically plateaus
Weight Gain 3yrs of Olanzapine (n=573)  vs Haloperidol (n=103) Treatment Data from Kinon (2001) J Clin Psychiatry 62:92-10...
Weight Gain During 3yrs of Olanzapine (n=573) by baseline weight 9.5kg 7kg 3kg Data from Kinon (2001) J Clin Psychiatry 62...
Weight gain seen in bipolar disorder too
Weight Gain During 32 weeks of Olanzapine (n=948) by baseline weight in bipolar disorder 8kg Lipkovich Early Predictors of...
Weight gain highest in drug-naive patients
2-Year   Weight Gain in First-Episode Schizophrenia: Effect of Type of Analysis Zipursky RB et al.  Br J Psychiatry . 2005...
EUFEST – randomised controlled 12-month trial (n=498) Kahn RS et al. Effectiveness of antipsychotic drugs in first-episode...
CAFE study – weight and related measures in first-episode schizophrenia McEvoy et al 2007 5.7 Weight change * * 7.0 11.0 3...
Summary of Metabolic Complications <ul><li>We have summarized all existing data of studies measuring metabolic problems in...
 
… .and against general population rates?
 
… are patients monitored for these problems? <ul><li>Mitchell AJ, Delaffon V, Vancampfort D, Correll CU, De Hert M. </li><...
Psychol Med. 2011 Aug 10:1-23. [Epub ahead of print]
Can metabolic complications be avoided?  <ul><li>Yes by…. </li></ul><ul><li>By switching to a weight sparing antipsychotic...
Estimated Weight Change (lb)   After Switch to Ziprasidone † † Repeated measures analysis Improvement Presented at APA 200...
Alvarez-Jiménez– lifestyle in Unmedicated 1st Episode  (10-14 sessions over 3mo) Alvarez-Jiménez M J Clin Psychiatry. 2006...
Chen – Metformin after 3mo of Olanzapine Rx Chen et al (2008) Metformin for metabolic dysregulation in schizophrenic patie...
Metformin Coprescription at start of Olanzapine Wu et al Metformin Addition Attenuates Olanzapine-Induced Weight Gain in D...
Metformin in patients on antipsychotic drugs: a systematic review and meta-analysis Bjorkhem-Bergman  Journal of Psychopha...
Alex J  Mitchell  www.psycho-oncology.info University of Leicester (UK) Acknowledgements Davy Vancampfort, Belgium Marc De...
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Weight diabetes and metabolic problems in patients taking atypical antipsychotics (ajmitchell)

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Free slide show on weight gain, diabetes and metabolic problems in those taking atypical antipsychotic medication in schizophrenia, bipolar disorder and related conditions. Image credits retained by original authors. Please give correct acknolwedgements if you present any material from here.

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  • Arch Gen Psychiatry. 2007 Oct;64(10):1123-31. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Saha S , Chant D , McGrath J . Source Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol Q4076, Australia. Abstract CONTEXT: Despite improvements in mental health services in recent decades, it is unclear whether the risk of mortality in schizophrenia has changed over time. OBJECTIVE: To explore the distribution of standardized mortality ratios (SMRs) for people with schizophrenia. DATA SOURCES: Broad search terms were used in MEDLINE, PsychINFO, Web of Science, and Google Scholar to identify all studies that investigated mortality in schizophrenia, published between January 1, 1980, and January 31, 2006. References were also identified from review articles, reference lists, and communication with authors. STUDY SELECTION: Population-based studies that reported primary data on deaths in people with schizophrenia. DATA EXTRACTION: Operationalized criteria were used to extract key study features and mortality data. DATA SYNTHESIS: We examined the distribution of SMRs and pooled selected estimates using random-effects meta-analysis. We identified 37 articles drawn from 25 different nations. The median SMR for all persons for all-cause mortality was 2.58 (10%-90% quantile, 1.18-5.76), with a corresponding random-effects pooled SMR of 2.50 (95% confidence interval, 2.18-2.43). No sex difference was detected. Suicide was associated with the highest SMR (12.86); however, most of the major causes-of-death categories were found to be elevated in people with schizophrenia. The SMRs for all-cause mortality have increased during recent decades (P = .03). CONCLUSIONS: With respect to mortality, a substantial gap exists between the health of people with schizophrenia and the general community. This differential mortality gap has worsened in recent decades. In light of the potential for second-generation antipsychotic medications to further adversely influence mortality rates in the decades to come, optimizing the general health of people with schizophrenia warrants urgent attention.
  • Schizophr Res. 2000 Sep 29;45(1-2):21-8. Mortality and causes of death in schizophrenia in Stockholm county, Sweden. Osby U , Correia N , Brandt L , Ekbom A , Sparén P . Source Department of Psychiatry, Löwenströmska Hospital, Upplands Väsby, Sweden. urban.osby@nvso.sll.se Abstract A study of mortality for all patients with a first hospital diagnosis of schizophrenia in Stockholm County, Sweden, during 1973 to 1995 was performed, by linking the in-patient register with the national cause-of-death register. Overall and cause-specific standardized mortality ratios (SMR) were calculated by 5-year age classes and 5-year calendar time periods. The number of excess deaths was calculated by reducing the observed number of deaths by those expected. Our results confirmed a marked increase in mortality in schizophrenia both in males and females. Natural (somatic) causes of death was the main cause of excess deaths, with more than half of the excess deaths in females, and almost half of the excess deaths in males. Suicide was the specific cause of the largest number of excess deaths in males, while in females it was cardiovascular disease. SMRs were increased in both natural and unnatural causes of death, with 2.8 for males and 2.4 for females for all deaths, but were highest in suicide with 15.7 for males and 19.7 for females, and in unspecified violence with 11.7 for males and 9.9 for females. SMRs in suicide were especially high in young patients in the first year after the first diagnosis.
  • Prev Chronic Dis. 2006 April; 3(2): A42. Published online 2006 March 15. PMCID: PMC1563985 Copyright notice PEER REVIEWED Congruencies in Increased Mortality Rates, Years of Potential Life Lost, and Causes of Death Among Public Mental Health Clients in Eight States Craig W Colton, PhD and Ronald W Manderscheid, PhD Craig W Colton, Colton &amp; Associates; 475 West 2400 South, Bountiful, UT 84010, Phone: 801-299-1921, Email: [email_address] . Contributor Information . Corresponding author. This article has been cited by other articles in PMC.  Other Sections▼ Abstract Introduction Methods Results Discussion References Abstract Introduction Mortality rates are used as global measures of a population&apos;s health status and as indicators for public health efforts and medical treatments. Elevated mortality rates among individuals with mental illness have been reported in various studies, but very little focus has been placed on interstate comparisons and congruency of mortality and causes of death among public mental health clients. Methods Using age-adjusted death rates, standardized mortality ratios, and years of potential life lost, we compared the mortality of public mental health clients in eight states with the mortality of their state general populations. The data used in our study were submitted by public mental health agencies in eight states (Arizona, Missouri, Oklahoma, Rhode Island, Texas, Utah, Vermont, and Virginia) for 1997 through 2000 during the Sixteen-State Study on Mental Health Performance Measures, a multistate study federally funded by the Center for Mental Health Services in collaboration with the National Association of State Mental Health Program Directors. Results In all eight states, we found that public mental health clients had a higher relative risk of death than the general populations of their states. Deceased public mental health clients had died at much younger ages and lost decades of potential life when compared with their living cohorts nationwide. Clients with major mental illness diagnoses died at younger ages and lost more years of life than people with non-major mental illness diagnoses. Most mental health clients died of natural causes similar to the leading causes of death found nationwide, including heart disease, cancer, and cerebrovascular, respiratory, and lung diseases. Conclusion Mental health and physical health are intertwined; both types of care should be provided and linked together within health care delivery systems. Research to track mortality and primary care should be increased to provide information for additional action, treatment modification, diagnosis-specific risk, and evidence-based practices.
  • Lancet. 2011 Aug 27;378(9793):815-25. Health and economic burden of the projected obesity trends in the USA and the UK. Wang YC , McPherson K , Marsh T , Gortmaker SL , Brown M . Abstract Rising prevalence of obesity is a worldwide health concern because excess weight gain within populations forecasts an increased burden from several diseases, most notably cardiovascular diseases, diabetes, and cancers. In this report, we used a simulation model to project the probable health and economic consequences in the next two decades from a continued rise in obesity in two ageing populations--the USA and the UK. These trends project 65 million more obese adults in the USA and 11 million more obese adults in the UK by 2030, consequently accruing an additional 6-8·5 million cases of diabetes, 5·7-7·3 million cases of heart disease and stroke, 492,000-669,000 additional cases of cancer, and 26-55 million quality-adjusted life years forgone for USA and UK combined. The combined medical costs associated with treatment of these preventable diseases are estimated to increase by $48-66 billion/year in the USA and by £1·9-2 billion/year in the UK by 2030. Hence, effective policies to promote healthier weight also have economic benefits. Copyright © 2011 Elsevier Ltd. All rights reserved. Comment on
  • Lancet. 2011 Aug 27;378(9793):804-14. The global obesity pandemic: shaped by global drivers and local environments. Swinburn BA , Sacks G , Hall KD , McPherson K , Finegood DT , Moodie ML , Gortmaker SL . Source WHO Collaborating Centre for Obesity Prevention, Deakin University, Melbourne, VIC, Australia. boyd.swinburn@deakin.edu.au Abstract The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers. Copyright © 2011 Elsevier Ltd. All rights reserved.
  • Willet et al. Guidelines for Healthy Weight (1999) NEJM 341, 427 - 433
  • World Health Organization. http://www.who.int/healthinfo/global_burden_disease/global_health_risks/en/index.htm
  • Comparison of Metabolic Syndrome and Individual Criterion Prevalence: Fasting CATIE vs Matched NHANES III Subjects This table compares rates of NCEP ATP III criteria for metabolic syndrome in patients with schizophrenia vs normal controls. The analysis included patients with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and a randomly selected sample from NHANES III, matched 1:1 on the basis of age, sex, and race/ethnicity. In men and women alike, the prevalence of metabolic syndrome was significantly higher in patients with schizophrenia versus matched controls. Correspondingly, men as well as women with schizophrenia had significantly higher rates of each of the NCEP ATP III criteria for metabolic syndrome, including waist circumference, triglyceride level, HDL-C level, and blood pressure level. The blood glucose criterion was significantly more prevalent in women with than without schizophrenia, whereas rates were similar in both groups of men. Reference McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res . 2005;80:19-32.
  • 66% of people with schizophrenia who have coronary heart disease (CHD) are less likely to be prescribed statins compared to 81% of other people with CHD. Lambert et al. Med J Aust 2003;178(Suppl):S67–S70
  • 66% of people with schizophrenia who have coronary heart disease (CHD) are less likely to be prescribed statins compared to 81% of other people with CHD. Lambert et al. Med J Aust 2003;178(Suppl):S67–S70
  • 66% of people with schizophrenia who have coronary heart disease (CHD) are less likely to be prescribed statins compared to 81% of other people with CHD. Lambert et al. Med J Aust 2003;178(Suppl):S67–S70
  • Lipkovich Early Predictors of Substantial Weight Gain in Bipolar Patients Treated with Olanzapine (J Clin Psychopharmacol 2006;26:316–320) To determine predictors of substantial weight gain (SWG) during treatment of bipolar disorder with olanzapine, data were pooled from 4 long-term randomized, multicenter studies in patients with bipolar mania or mixed mania (N = 948 at initiation of olanzapine). SWG was defined as gaining 5 kg or 7% of initial weight in 30 ± 2 weeks. Logistic regression estimated odds ratios associated with early weight gain and baseline risk factors for predicting SWG. A classification system to identify patients at risk for SWG was constructed by recursive data partitioning. Baseline characteristics significantly associated with SWG included younger age, nonwhite ethnicity, lower body mass index (BMI), nonrapid cycling, and psychotic features. Weight gain of 2 or more kg in the first 3 weeks of therapy predicted SWG by 30 weeks (sensitivity = 57%; specificity = 71%). A classification system with thresholds for early weight gain, baseline BMI, and ethnicity further improved SWG predictability (sensitivity = 79%; specificity = 70%). In conclusion, patients with bipolar disorder who gained 2 to 3 kg during the first 3 weeks of treatment with olanzapine, SWG was predicted after 30 weeks of treatment. Patients with less pronounced early weight gain might still be at risk for later SWG if they have close to normal BMI (27 kg/m2) at treatment initiation. (J Clin Psychopharmacol 2006;26:316–320)
  • 2-Year Weight Gain in First-Episode Schizophrenia: Effect of Type of Analysis The course of weight gain was evaluated in 263 patients with first-episode schizophrenia who were randomized to olanzapine or haloperidol in a 2-year, double-blind trial. The data were subjected to 2 types of analyses according to last observation carried forward (LOCF, shown on the left side of the slide) and observed cases (shown on the right side). These data show that the degree and course of weight gain varied considerably, depending on the type of analysis. The LOCF analysis showed that both treatment groups gained weight rapidly during the first 12 weeks of treatment. The pace of weight gain then tapered gradually and eventually stabilized after 1 year. In the olanzapine group, the mean weight gain was 7.3 kg at 12 weeks, 10.2 kg at 1 year, and 10.2 kg at 2 years. In the haloperidol group, the weight gains at these time points were 2.6 kg, 4.2 kg, and 4.0 kg, respectively. Compared with the LOCF analysis, the observed-cases analysis showed a longer course of steady weight gain, which lasted up to 60 weeks in the olanzapine group and up to 36 weeks in the haloperidol group. The overall weight gain was also higher according to this analysis. The mean weight gain in the olanzapine group was 9.2 kg at 12 weeks, 15.5 kg at 1 year, and 15.4 kg at 2 years. In the haloperidol group, the weight gains at these time points were 3.7 kg, 7.1 kg, and 7.5 kg, respectively. Reference Zipursky RB, Gu H, Green AI, et al. Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol. Br J Psychiatry . 2005;187:537-543.
  • Changes in weight were analyzed using a mixed random coefficients model similar to that used for the secondary efficacy measures. The olanzapine-treated group gained more weight than the quetiapine or risperidone groups at Weeks 12 and 52 ( P &lt;0.001). Women in the risperidone group had greater increases in weight and BMI than women in the quetiapine group. At Week 52, 80% of olanzapine-treated patients gained  7% of their baseline weight compared with 50% and 58% of quetiapine- and risperidone-treated patients (observed cases). The olanzapine-treated group had a higher proportion of patients with a ≥ 1 BMI unit increase than the quetiapine group at Week 12 and 52 and the risperidone group at Week 12. References Lieberman J, McEvoy JP, Perkins D, Hamer RH. Comparison of atypicals in first-episode psychosis: a randomized, 52-week comparison of olanzapine, quetiapine, and risperidone. Eur Neuropsychopharmacol . 2005;15(Suppl 3):S526. Marx CE. Comparison of atypicals in first-episode psychosis (CAFE): a randomized, double-blind, 52-week comparison of olanzapine, quetiapine, and risperidone. Paper presented at: 8 th World Congress of Biological Psychiatry; June 28 – July 3, 2005; Vienna, Austria.
  • Background: People with severe mental illnesses (SMI), including schizophrenia, are at increased risk of cardiovascular disease (CVD). Guidelines recommend regular CVD screening and in the United Kingdom, since 2004, General Practitioners are remunerated for annual reviews. Objectives: To compare annual rates of CVD screening provision in people with and without SMI between 2000 and 2008. Method: We identified 18,696 people with SMI and 95,512 people without SMI in the UK The Health Improvement Network (THIN) primary care database. We compared the rates of measurement of blood pressure (BP), glucose, cholesterol and body mass index (BMI). Results: Prior to 2004, all people with SMI, were significantly less likely to receive each measurement, (including people above and below 60 years of age). In 2003; adjusted incidence rate ratios (95% CI) for screening in people with SMI under 60 years compared to people without SMI were: BMI: 0.62 (0.58–0.65); BP: 0.59 (0.56–0.62); glucose: 0.66 (0.61–0.70) and cholesterol: 0.54 (0.49–0.59). By 2007 people with SMI under 60 were equally likely receive a measurement of BMI: 1.00 (0.96–1.04), glucose: 1.00 (0.96–1.05) and cholesterol: 0.95 (0.90–1.0); the gap in screening for BP had narrowed 0.87 (0.83–0.90). However people with SMI over 60 years of age remained significantly less likely to be screened. There was little difference in screening according to social deprivation. Conclusions: In UK primary care, people with SMI over 60 years of age remain less likely than the general population to receive annual CVD screening despite higher risk of developing CVD.
  • Psychol Med. 2011 Aug 10:1-23. [Epub ahead of print] Guideline concordant monitoring of metabolic risk in people treated with antipsychotic medication: systematic review and meta-analysis of screening practices. Mitchell AJ , Delaffon V , Vancampfort D , Correll CU , De Hert M . Source Psycho-oncology, Leicester General Hospital, Leicestershire Partnership Trust, Leicester, UK. Abstract BACKGROUND: Despite increased cardiometabolic risk in individuals with mental illness taking antipsychotic medication, metabolic screening practices are often incomplete or inconsistent.MethodWe undertook a systematic search and a PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) meta-analysis of studies examining routine metabolic screening practices in those taking antipsychotics both for patients in psychiatric care before and following implementation of monitoring guidelines. RESULTS: We identified 48 studies (n=290 534) conducted between 2000 and 2011 in five countries; 25 studies examined predominantly schizophrenia-spectrum disorder populations; 39 studies (n=218 940) examined routine monitoring prior to explicit guidelines; and nine studies (n=71 594) reported post-guideline monitoring. Across 39 studies, routine baseline screening was generally low and above 50% only for blood pressure [69.8%, 95% confidence interval (CI) 50.9-85.8] and triglycerides (59.9%, 95% CI 36.6-81.1). Cholesterol was measured in 41.5% (95% CI 18.0-67.3), glucose in 44.3% (95% CI 36.3-52.4) and weight in 47.9% (95% CI 32.4-63.7). Lipids and glycosylated haemoglobin (HbA1c) were monitored in less than 25%. Rates were similar for schizophrenia patients, in US and UK studies, for in-patients and out-patients. Monitoring was non-significantly higher in case-record versus database studies and in fasting samples. Following local/national guideline implementation, monitoring improved for weight (75.9%, CI 37.3-98.7), blood pressure (75.2%, 95% CI 45.6-95.5), glucose (56.1%, 95% CI 43.4-68.3) and lipids (28.9%, 95% CI 20.3-38.4). Direct head-to-head pre-post-guideline comparison showed a modest but significant (15.4%) increase in glucose testing (p=0.0045). CONCLUSIONS: In routine clinical practice, metabolic monitoring is concerningly low in people prescribed antipsychotic medication. Although guidelines can increase monitoring, most patients still do not receive adequate testing. PMID: 21846426 [PubMed - as supplied by publisher]
  • Background: People with severe mental illnesses (SMI), including schizophrenia, are at increased risk of cardiovascular disease (CVD). Guidelines recommend regular CVD screening and in the United Kingdom, since 2004, General Practitioners are remunerated for annual reviews. Objectives: To compare annual rates of CVD screening provision in people with and without SMI between 2000 and 2008. Method: We identified 18,696 people with SMI and 95,512 people without SMI in the UK The Health Improvement Network (THIN) primary care database. We compared the rates of measurement of blood pressure (BP), glucose, cholesterol and body mass index (BMI). Results: Prior to 2004, all people with SMI, were significantly less likely to receive each measurement, (including people above and below 60 years of age). In 2003; adjusted incidence rate ratios (95% CI) for screening in people with SMI under 60 years compared to people without SMI were: BMI: 0.62 (0.58–0.65); BP: 0.59 (0.56–0.62); glucose: 0.66 (0.61–0.70) and cholesterol: 0.54 (0.49–0.59). By 2007 people with SMI under 60 were equally likely receive a measurement of BMI: 1.00 (0.96–1.04), glucose: 1.00 (0.96–1.05) and cholesterol: 0.95 (0.90–1.0); the gap in screening for BP had narrowed 0.87 (0.83–0.90). However people with SMI over 60 years of age remained significantly less likely to be screened. There was little difference in screening according to social deprivation. Conclusions: In UK primary care, people with SMI over 60 years of age remain less likely than the general population to receive annual CVD screening despite higher risk of developing CVD.
  • Psychol Med. 2011 Aug 10:1-23. [Epub ahead of print] Guideline concordant monitoring of metabolic risk in people treated with antipsychotic medication: systematic review and meta-analysis of screening practices. Mitchell AJ , Delaffon V , Vancampfort D , Correll CU , De Hert M . Source Psycho-oncology, Leicester General Hospital, Leicestershire Partnership Trust, Leicester, UK. Abstract BACKGROUND: Despite increased cardiometabolic risk in individuals with mental illness taking antipsychotic medication, metabolic screening practices are often incomplete or inconsistent.MethodWe undertook a systematic search and a PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) meta-analysis of studies examining routine metabolic screening practices in those taking antipsychotics both for patients in psychiatric care before and following implementation of monitoring guidelines. RESULTS: We identified 48 studies (n=290 534) conducted between 2000 and 2011 in five countries; 25 studies examined predominantly schizophrenia-spectrum disorder populations; 39 studies (n=218 940) examined routine monitoring prior to explicit guidelines; and nine studies (n=71 594) reported post-guideline monitoring. Across 39 studies, routine baseline screening was generally low and above 50% only for blood pressure [69.8%, 95% confidence interval (CI) 50.9-85.8] and triglycerides (59.9%, 95% CI 36.6-81.1). Cholesterol was measured in 41.5% (95% CI 18.0-67.3), glucose in 44.3% (95% CI 36.3-52.4) and weight in 47.9% (95% CI 32.4-63.7). Lipids and glycosylated haemoglobin (HbA1c) were monitored in less than 25%. Rates were similar for schizophrenia patients, in US and UK studies, for in-patients and out-patients. Monitoring was non-significantly higher in case-record versus database studies and in fasting samples. Following local/national guideline implementation, monitoring improved for weight (75.9%, CI 37.3-98.7), blood pressure (75.2%, 95% CI 45.6-95.5), glucose (56.1%, 95% CI 43.4-68.3) and lipids (28.9%, 95% CI 20.3-38.4). Direct head-to-head pre-post-guideline comparison showed a modest but significant (15.4%) increase in glucose testing (p=0.0045). CONCLUSIONS: In routine clinical practice, metabolic monitoring is concerningly low in people prescribed antipsychotic medication. Although guidelines can increase monitoring, most patients still do not receive adequate testing. PMID: 21846426 [PubMed - as supplied by publisher]
  • See Stroup TS, McEvoy JP, Ring KD, Hamer RH, LaVange LM, Swartz MS, Rosenheck RA, Perkins DO, Nussbaum AM, Lieberman JA. Comparison of antipsychotics for metabolic problems (CAMP):a randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk. American Journal of Psychiatry. Online ahead of print July 18, 2011.
  • J Clin Psychiatry. 2006 Aug;67(8):1253-60. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: A randomized controlled trial. Alvarez- Jiménez M , González -Blanch C , Vázquez-Barquero JL , Pérez-Iglesias R , Martínez-García O , Pérez-Pardal T , Ramírez -Bonilla ML , Crespo-Facorro B . Source University Hospital Marqués de Valdecilla Clinical and Social Psychiatry Research Unit, Department of Psychiatry, Santander, Spain. Abstract BACKGROUND: The purpose of this study was to compare an early behavioral intervention (EBI) with nonstructured standard physical care (routine care intervention [RCI]) in preventing antipsychotic-induced weight gain in drug-naive first-episode psychosis patients. METHOD: Sixty-one patients with a DSM-IV-diagnosed psychotic disorder were first randomly assigned to 3 different antipsychotic treatments (risperidone [N = 23], olanzapine [N = 18], and haloperidol [N = 21]) and subsequently randomly assigned to the intervention condition (EBI, N = 35) or RCI (N = 27). EBI was specifically designed to teach strategies to enhance control over factors associated with antipsychotic-induced weight gain and consisted of 8 flexible intervention modules that incorporated behavioral interventions, nutrition, and exercise. In the RCI group, patients were informed about potential weight gain and advised to increase their exercise and limit food intake. Body weight and body mass index were measured at baseline and then weekly for 3 months. In addition to change in weight and body mass index, a third outcome measure was the proportion of patients who had gained more than 7% of their body weight at 3 months. Participating patients were referred between August 2002 and September 2004. RESULTS: All 61 participants completed the study. Patients in the EBI group gained significantly less weight (mean = 4.1 kg, SD = 4.0) than those allocated to the RCI group (mean = 6.9 kg, SD = 4.5) (p &lt; .01) during the 3-month follow-up period. Similar findings were obtained when both groups were compared on treatment-induced change in body mass index, which was significantly less in the EBI group than in the RCI group (1.40 vs. 2.39 kg/m2) (p &lt; .01). Accordingly, significantly fewer patients in the EBI group (N = 11; 39.3%) than in the RCI group (N = 26; 78.8%) (p &lt; .002) increased their baseline weight by more than 7%, the cutoff for clinically meaningful weight gain. CONCLUSIONS: EBI was effective in attenuating antipsychotic-induced weight gain in a drug-naive first-episode psychosis cohort. Patients displayed good adherence to this type of preventive intervention.
  • Metformin for weight reduction in non-diabetic patients on antipsychotic drugs: a systematic review and meta-analysis Linda Bjorkhem-Bergman, Annika B Asplund and Jonatan D Lindh Bjorkhem-Bergman Journal of Psychopharmacology 2010; 25(3) 299–305 Abstract Weight gain is a clinically important side effect of antipsychotic drug therapy. The aim of this study was to determine the effect of the antidiabetic drug metformin on antipsychotic-induced weight gain in non-diabetic patients. In a systematic literature review we identified 195 citations from which seven randomized, placebo-controlled studies (398 patients) were included in the final analysis. Studies in adults (n ¼5) and in children (n ¼2) were analysed separately. Compared with placebo, metformin treatment caused a significant body weight reduction in adult non-diabetic patients treated with atypical antipsychotics (4.8%, 95% CI 1.6 to 8.0) and in children (4.1%, 95% CI 2.2 to 6.0). There was evidence of substantial heterogeneity among studies, and when the analysis was restricted to patients with a manifest (&gt;10%) body weight increase prior to randomisation metformin reduced weight by 7.5% (95% CI 2.9 to 12.0). The effect was larger in Asians (7.8%, 95% CI 4.4 to 11.2) than in Hispanics (2.0%, 95% CI 0.7 to 3.3). In conclusion, metformin has a pronounced weight-reducing effect in antipsychotic-treated patients, especially in those with a manifest weight gain. Although direct comparisons are lacking, the observed effect on body weight compares favourably with the effect of sibutramine and orlistat, approved for weight reduction. However, metformin is not approved for use in non-diabetic patients and it is still not generally advisable to recommend metformin to counteract antipsychotic-induced weight gain.
  • Weight diabetes and metabolic problems in patients taking atypical antipsychotics (ajmitchell)

    1. 1. Alex J Mitchell www.psycho-oncology.info University of Leicester (UK) Acknowledgements Davy Vancampfort, Belgium Marc De Hert, Belgium Weight Gain, Diabetes and Metabolic Problems in Patients prescribed Atypical Antipsychotics Online Information Oct 2011. Only use these slides for personal use and/or with credit to the author
    2. 2. I. Background
    3. 3. What are Severe Mental Health problems? <ul><li>These usually include </li></ul><ul><li>Schizophrenia and related disorders </li></ul><ul><li>Bipolar Affective Disorder (prev known as manic-depression) </li></ul><ul><li>Severe depression </li></ul><ul><li>These conditions are sometimes collectively called “ SMI ” and tend to be the ones where are antipsychotic is prescribed </li></ul>
    4. 4. Is there Accelerated mortality in SMI? <ul><li>Yes, there is premature mortality by 20 years on average </li></ul><ul><li>This “mortality gap” has been increasing, as shown over…. </li></ul>
    5. 5. Schizophrenia –Standardized Mortality Ratio Pooled estimate=2.50 (95% CI=2.18-2.83) > > > > Saha Arch Gen Psychiatry. 2007 Oct;64(10):1123-31 .
    6. 6. Mortality trends in Stockholm County 1976–79 to 1990–95, cardiovascular causes of death *Controlling for age at first diagnosis and years of follow-up **Standardised by the sex and age distribution of the patients Data from Osby et al 2000 0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1976–79 1980–85 1986–89 1990–95 Deaths/100,000 19 76–79 period of reference Patients with schizophrenia* General population**
    7. 7. Cardiovascular disease is primary cause of death in persons with mental illness* *Average data from 1996–2000 Data From Colton & Manderscheid 2006 Percentage of deaths 50 40 20 10 0 30 Heart disease Cancer Cerebrovascular Chronic respiratory Diabetes Influenza/pneumonia Accidents Suicide MO OK RI TX UT VA
    8. 8. What is the Concern Re Obesity in the Popn? <ul><li>In 1950 </li></ul><ul><li>25% US adults were overweight (BMI > 25) </li></ul><ul><li>In 2005 </li></ul><ul><li>25% were obese (BMI > 30) </li></ul><ul><li>In 1998 </li></ul><ul><li>25% of children were overweight </li></ul><ul><li>By 2012 </li></ul><ul><li>Only 25% of the US population will not be overweight </li></ul><ul><li>BMI = weight / height squared </li></ul>
    9. 11. Obesity increases the risk of disease Willet et al. Guidelines for Healthy Weight (1999) NEJM 341, 427 - 433
    10. 12. Which Risk Factors Are Important? <ul><li>For cardiovascular disease and general mortality… </li></ul><ul><li>Blood pressure (BP) </li></ul><ul><li>Smoking </li></ul><ul><li>Inactivity (fitness) </li></ul><ul><li>Weight / obesity </li></ul><ul><li>Cholesterol / lipids </li></ul>
    11. 13. Ranking of selected risk factors: 6 leading causes of death by income group, estimates for 2004 Percentage of total (total: 1.53 billion) World Health Organization . http://www.who.int/healthinfo/global_burden_disease/global_health_risks/en/index.htm
    12. 14. The following are important for diabetes IFG BP Waist HDL TG <ul><ul><li>≥ 102 cm or 40 inches (m) </li></ul></ul><ul><ul><li>≥ 88 cm or 36 inches(f) </li></ul></ul><ul><ul><li>≥ 150 mg/dl </li></ul></ul><ul><ul><li>< 40 mg/dL (m) </li></ul></ul><ul><ul><li>< 50 mg/dL (f) </li></ul></ul><ul><ul><li>≥ 130/85 mmHg </li></ul></ul>≥ 6.1 mmol/L (110 mg/dl). TG = triglycerides; IFG = impaired fasting glucose; HDL = high density lipids Collectively known as “metabolic syndrome” (when 3x are present)
    13. 15. How Many Antipsychotics are prescribed? <ul><li>About 6million prescriptions in the UK per year </li></ul><ul><li>Perhaps to 0.5 million people in the UK annually (estimated) </li></ul><ul><li>Globally they generate about 20billion per year for the pharmaceutical industry </li></ul><ul><li>They are prescribed for several mental health conditions </li></ul><ul><li>About 15% are given to the under 18’s </li></ul>
    14. 16. Source: IMS; Robert Rosenheck MD Global Antipsychotic Market Sales (MAT Q1 by Yr)
    15. 17. Most common uses of atypical antipsychotics Off label use accounts for ~ 1/3 of prescriptions
    16. 19. II. Weight, diabetes complications of Atypicals The following are of high concern in SMI (next slide)
    17. 20. IFG BP Waist HDL TG <ul><ul><li>≥ 102 cm or 40 inches (m) </li></ul></ul><ul><ul><li>≥ 88 cm or 36 inches(f) </li></ul></ul><ul><ul><li>≥ 150 mg/dl </li></ul></ul><ul><ul><li>< 40 mg/dL (m) </li></ul></ul><ul><ul><li>< 50 mg/dL (f) </li></ul></ul><ul><ul><li>≥ 130/85 mmHg </li></ul></ul>≥ 6.1 mmol/L (110 mg/dl ). Diab Smoking
    18. 21. Prevalence of diabetes in schizophrenia compared to general population 8.6% diabetes; n=415 Slide thanks to De Hert et al 2006 15 Age group (years) General population Patients 15–25 25–35 35–45 45–55 55–65 0 5 10 20 25 30 0.4 2.0 0.9 1.1 6.1 25.0 5.8 Prevalence of diabetes (%) 3.2 2.4 12.7
    19. 22. Bipolar comparison study – prevalence of metabolic disturbances van Winkel et al 2008 72.3 59.8 71.6 17.0 29.3 22.1 10.7 10.9 6.4 0 10 20 30 40 50 60 70 80 90 100 Bipolar (n=112) Schizoaffective (n=92) Schizophrenia (n=503) Prevalence of metabolic disturbances (%) Normal glucose values (n=496) Pre-diabetes (n=157) Diabetes (n=54)
    20. 23. BMI change after 52 weeks of olanzapine in bipolar patients Image Credit: Hennen (2004)
    21. 24. Antipsychotic-induced diabetes mellitus..warning in 2003 <ul><li>October 20, 2003 </li></ul><ul><li>FDA warns diabetes and antipsychotic medications </li></ul><ul><li>FDA to require diabetes warning on antipsychotics </li></ul><ul><li>In a series of letters delivered in mid-September, the US FDA disclosed to makers of atypical antipsychotic medications that it will require each drug maker to re-label its product to include warnings regarding risk of hyperglycaemia and diabetes mellitus </li></ul>
    22. 25. About the CATIE Study of Atypicals….. <ul><li>• Non-industry sponsored. </li></ul><ul><li>• 1493 patients. </li></ul><ul><li>• 18 month double blind. </li></ul><ul><li>• Olanzapine, quetiapine, risperidone, ziprasidone & perphenazine </li></ul><ul><li>74% discontinued before 18 months, median 4.6 months. Olanzapine 9.2 months </li></ul><ul><li>Metabolic problems much greater versus general population </li></ul><ul><li>Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209–1223 </li></ul>
    23. 26. Comparison of Metabolic Syndrome and Individual Criterion Prevalence: Fasting CATIE vs Matched NHANES III Subjects CATIE = Clinical Antipsychotic Trials of Intervention Effectiveness; NHANES = National Health and Nutrition Examination Survey. McEvoy JP et al. Schizophr Res . 2005;80:19-32. Men Women CATIE (%) (N=509) NHANES (%) (N=509) P CATIE (%) (N=180) NHANES III (%) (N=180) P Metabolic syndrome prevalence 36.0 19.7 .0001 51.6 25.1 .0001 Waist circumference criterion 35.5 24.8 .0001 76.3 57.0 .0001 Triglyceride criterion 50.7 32.1 .0001 42.2 19.6 .0001 HDL criterion 48.9 31.9 .0001 63.3 36.3 .0001 BP criterion 47.2 31.1 .0001 46.9 26.8 .0001 Glucose criterion 14.1 14.2 .9635 21.7 11.2 .0075
    24. 27. CATIE: rates of pharmacological interventions for abnormal blood pressure, lipids and glucose Nasrallah et al 2006 n=1488 n=685 n=690 Patients (%) n=481 n=300 n=75 n=34 n=471 n=421 33.2 10.9 68.3 62.4 45.3 89.4 0 20 40 60 80 100 Hypertension Diabetes Dyslipidaemia Prevalence Lack of medical intervention
    25. 28. But not everyone gains weight….
    26. 29. 20% do not gain weight over 2yrs of Olanzapine Treatment Data from Basson, Kinon JCP
    27. 30. Weight gain begins early, typically plateaus
    28. 31. Weight Gain 3yrs of Olanzapine (n=573) vs Haloperidol (n=103) Treatment Data from Kinon (2001) J Clin Psychiatry 62:92-100; Image Credit: JCP / Physicians Press 7kg
    29. 32. Weight Gain During 3yrs of Olanzapine (n=573) by baseline weight 9.5kg 7kg 3kg Data from Kinon (2001) J Clin Psychiatry 62:92-100; Image Credit: JCP / Physicians Press
    30. 33. Weight gain seen in bipolar disorder too
    31. 34. Weight Gain During 32 weeks of Olanzapine (n=948) by baseline weight in bipolar disorder 8kg Lipkovich Early Predictors of Substantial Weight Gain in Bipolar Patients Treated with Olanzapine. J Clin Psychopharm 2006;26:316-320 6kg 4.5kg
    32. 35. Weight gain highest in drug-naive patients
    33. 36. 2-Year Weight Gain in First-Episode Schizophrenia: Effect of Type of Analysis Zipursky RB et al. Br J Psychiatry . 2005;187:537-543. OLZ = olanzapine HAL = Haloperidol 18 16 14 12 10 8 6 4 2 0 0 10 20 30 40 50 60 70 80 90 100 110 OLZ( Yr 1): n=35 OLZ (Yr 2): n=13 HAL (Yr 1): n=47 HAL (Yr 2): n=28 15.4 kg 7.5 kg Week of Therapy
    34. 37. EUFEST – randomised controlled 12-month trial (n=498) Kahn RS et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet . 2008 Mar 29 ; 371(9618):1085-97 Haloperidol Amisulpride Olanzapine Quetiapine Ziprasidone 0 10 20 30 40 50 60 70 80 90 Weight gain >7% from baseline (%) p=0.053* 53 63 86% 65 37 0 2 4 6 8 10 12 14 16 7.3 9.7 13.9 4.8 10.5 p<0.0001* Weight change from baseline (kg)
    35. 38. CAFE study – weight and related measures in first-episode schizophrenia McEvoy et al 2007 5.7 Weight change * * 7.0 11.0 3.7 4.0 6.6 0 2 4 6 8 10 12 Week 12 Week 52 Least squares mean change (kg) Risperidone (n=133) Quetiapine (n=134) Olanzapine (n=133) 0 20 40 60 80 100 Week 12 Week 52 Percentage of patients ** ** 80.0 50.0 58.0 60.0 29.0 32.0 Weight gain  7% #
    36. 39. Summary of Metabolic Complications <ul><li>We have summarized all existing data of studies measuring metabolic problems in three groups: </li></ul><ul><li>Established schizophrenia </li></ul><ul><li>Vs early (first epsiode schizophrenia) </li></ul><ul><li>Vs unmedicated patients with schizophrenia </li></ul>
    37. 41. … .and against general population rates?
    38. 43. … are patients monitored for these problems? <ul><li>Mitchell AJ, Delaffon V, Vancampfort D, Correll CU, De Hert M. </li></ul><ul><li>Guideline concordant monitoring of metabolic risk in people treated with antipsychotic medication: systematic review and meta-analysis of screening practices. </li></ul><ul><li>Psychol Med. 2011 Aug 10:1-23. [Epub ahead of print] </li></ul>
    39. 44. Psychol Med. 2011 Aug 10:1-23. [Epub ahead of print]
    40. 45. Can metabolic complications be avoided? <ul><li>Yes by…. </li></ul><ul><li>By switching to a weight sparing antipsychotic </li></ul><ul><li>By giving lifestyle advice and assistance </li></ul><ul><li>By adding in weight loss medication (early or late) </li></ul><ul><li>By avoiding weight gaining antipsychotics (only a few exist) </li></ul>
    41. 46. Estimated Weight Change (lb) After Switch to Ziprasidone † † Repeated measures analysis Improvement Presented at APA 2004, New York, NY Conventionals Olanzapine Risperidone -25 -20 -15 -10 -5 0 5 LS Mean Change, lb 49 53 58 45 40 36 32 27 23 19 14 10 6 Weeks * *** *** ** ** *** * P <0.05 ** P <0.001 *** P <0.0001 Switched from
    42. 47. Alvarez-Jiménez– lifestyle in Unmedicated 1st Episode (10-14 sessions over 3mo) Alvarez-Jiménez M J Clin Psychiatry. 2006 Aug;67(8):1253-60. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: A randomized controlled trial.
    43. 48. Chen – Metformin after 3mo of Olanzapine Rx Chen et al (2008) Metformin for metabolic dysregulation in schizophrenic patients treated with olanzapine. Progress in Neuro-Psychopharmacology & Biological Psychiatry 32 (2008) 925–931
    44. 49. Metformin Coprescription at start of Olanzapine Wu et al Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: Am J Psychiatry 2008; 165:352–358
    45. 50. Metformin in patients on antipsychotic drugs: a systematic review and meta-analysis Bjorkhem-Bergman Journal of Psychopharmacology 2010; 25(3) 299–305
    46. 51. Alex J Mitchell www.psycho-oncology.info University of Leicester (UK) Acknowledgements Davy Vancampfort, Belgium Marc De Hert, Belgium Weight Gain, Diabetes and Metabolic Problems in Patients prescribed Atypical Antipsychotics Online Information Oct 2011

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