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Das: Physical Health in the In-Patient Mental Health Setting
- 1. Physical Health Care in the Mental Health In-Setting Dr Mrigendra Das Clinical Lead, Consultant Psychiatrist Broadmoor High Secure Hospital United Kingdom
- 4. A view
- 9. Broadmoor High Secure Hospital
- 16. Cardiovascular risk factors – overview BMI = body mass index; TC = total cholesterol; DM = diabetes mellitus; HTN = hypertension Wilson PWF et al . Circulation. 1998;97:1837–1847; *Data using Framingham study cohort; Dawber TR et al. Am J Public Health 1951;41:279 The Framingham Study* 0 2 4 6 8 10 12 14 HTN DM Smoking BMI >27 TC >220 Single risk factors Multiple risk factors Odds ratios Smoking + BMI 2 Smoking + BMI + TC >220 3 Smoking + BMI + TC >220 + DM 4 Smoking + BMI + TC >220 + DM + HTN 5
- 17. Cardiovascular risk factors and schizophrenia 1. Allison DB et al . Am J Psychiatry. 1999;156(11):1686 – 1696; 2. Herran A et al. Schizophr Res . 2000;41(2):373–381; 3. Goff DC et al. J Clin Psychiatry 2005;66:183–94; 4. Davidson S et al. Aust N Z J Psychiatry . 2001;35(2):196–202. Dyslipidaemia 4 Hypertension 4 Age Diabetic control 3 Personal history Smoking 2 Family history Obesity 1 Gender Modifiable risk factors Non-modifiable risk factors
- 19. Prevalance of Metabolic Syndrome (Yadav etal 2009) Description n(%) Description n(%) Metabolic syndrome 75(53) Atypical antipsychotics 66(47) Caucasian 101(72) Clozapine 33 (25) Black 23(16) Olanzapine 14(11) Asian 8(6) Quetiapine 11(8) Mixed Race 8(6) Risperidone 12(9) Smoker 101 (72) Typical Antipsychotics 21(16) Schizophrenia spectrum 100(71) Typical and atypical Antipsych 10(7) Personality Disorder 36(25) Mood Stabiliser 25(18) Mood Disorder 2(1) Valproate 17(12) Autistic Spectrum 2(1) Other antidepressant 8 (6)
- 20. Relative risk for diabetes and cardiovascular disease among patients with the Metabolic Syndrome (13 studies)* 1-Circulation, 2004;109:42-46 2-Circulation, 2003;108:414-419 3-Diabetes Care 2005;28(2):385-90 4-Circulation 2004;110:1239-1244 5-JAMA 2002;289:2709-2716 6-Am J Card 2004;93(2):136-141 diabetes 7-Circulation 2003;107:391-397 8-Arch Int Med 2004;164:1066-1076 9-Diabetes Care 2001;24:683-689 10-Atheroschlerosis 2004; 173:309-314 11-Circulation 2004;110:1245-1251 12-Diabetes Care 2003;26:3153-3159 13-EASD 2004
- 21. CHD risk increases with increasing number of metabolic syndrome risk factors (3 separate studies) Sattar et al, Circulation. 2003;108:414–419 Whyte et al, American Diabetes Association , 2001 Adapted from Ridker, Circulation. 2003;107:393–339 Number of metabolic risk factors
- 22. Prevalence of metabolic syndrome according to BMI “ Overweight” = BMI 25-29.9; “obese” = BMI 30 (National Heart, Lung and Blood Institute, Obesity Guidelines); N=12,363; Data using NCEP ATP III definition for metabolic syndrome 0 10 20 30 40 50 60 70 Prevalence (%) Healthy Overweight Obese Healthy Overweight Obese Men Women Park YW et al. Arch Intern Med. 2003;163:427–436
- 23. Visceral adiposity and drug-na ïve schizophrenia 1 Thakore JH et al. Int J Obes Relat Metab Disord. 2002;26(1):137–141; 2 Ryan MC et al. Life Sci. 2004;74(16):1999–2008; 3 Zhang ZJ, Yao ZJ, Liu W et al. Br J Psychiatry. 2004;184:58–62 Not significant Age, gender, BMI and waist circumference 10 chronic patients, 10 controls Meyer (Submitted) Not significant Age, gender 46 first-episode, drug-naïve patients in Nanjing, China, 46 controls Zhang ZJ et al. (2004) 3 Greater IAF in patients with schizophrenia Age, gender 19 first-episode, drug-naïve patients in Dublin, 19 controls Ryan MC et al. (2004) 2 3x greater IAF in patients with schizophrenia Age, gender 15 drug-naïve patients or drug-free for 6 weeks in Dublin, 15 controls Thakore JH et al. (2002) 1 Intra-abdominal fat (IAF) mass Matching variables N Study
- 24. Short-term mean change in weight with some antipsychotics 1 Adapted from: Allison DB et al. Am J Psychiatry. 1999(Nov);156(11):1686–1696 . 2 Marder et al. Schizophr Res. 2003; 61:123–126 ; 3 Jon es et al. Presentation at ACNP. 1999 Estimated weight change at 10 weeks on ‘standard’ dose Haloperidol Risperidone Olanzapine Clozapine 6 Weight change (kg) 5 4 3 2 1 0 -1 -2 -3 Placebo Fluphenazine Ziprasidone Chlorpromazine 13.2 Weight change (lb) 11.0 8.8 6.6 4.4 2.2 0 -2.2 -4.4 -6.6 Quetiapine Aripiprazole Aripiprazole (4-6 week pooled data) 2 and quetiapine (6-week data) 2 added to analysis by Allison et al. Thioridazine/ mesoridazine
- 25. Clinically significant ( 7%) weight gain during antipsychotic treatment Abilify® [package insert]. Princeton NJ: Bristol-Myers Squibb and Rockville, Md: Otsuka America Pharmaceutical; 2005 ; Risperdal® [package insert]. Titiusville, NJ: Janssen Pharmaceutica Products, LP; 2003; Seroquel® [package insert]. Wilmington DE: AstraZeneca; 2004; Zyprexa® [package insert]. Indianapolis, Ind: Eli Lilly and Company; 2004. Incidence (%) 0 5 10 15 20 25 30 35 Placebo Aripiprazole Placebo Risperidone Placebo Quetiapine Placebo Olanzapine Data from package inserts (USA). Data obtained from different short-term (4-8 week) clinical studies. 0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 35
- 26. Aripiprazole vs olanzapine: mean weight change (26 week study) Baseline: aripiprazole = 80.8±1.85 kg; olanzapine = 80.4±1.84 kg (OC analysis) McQuade RD, et al, J Clin Psychiatry 2004;65(Suppl 18):47 – 56. 5.6kg Aripiprazole Olanzapine P ≤ 0.02 significantly greater than aripiprazole . N=274. * * * * * * * * * * * *
- 27. Prevalence of diabetes or IGT in schizophrenia IGT=impaired glucose tolerance; IFG=impaired fasting glucose; SCZ=schizophrenia; DM=diabetes mellitus 1. Ryan MC. et al . Am J Psychiatry. 2003;160:284-289; 2. Dixon L. et al. Schizophr Bull. 2000;26:903–912. — Current: 10.8% Lifetime: 14.9% Self-report of diabetes Field study: uncontrolled SCZ sample from 2 states (n=719) — 5.1% Self-report of diabetes vs NHANES III (n=18 825) — 11.1% Paid claim for diabetes Medicaid sample SCZ sample (n=6066) — 12.5% Paid claim for diabetes Medicare sample of SCZ adults (n=14,182) 2 Dixon et al (2000) <.02 15.4% vs 0% IFG ( 110 and 125 mg/dL) First episode, drug-naive inpatients with SCZ vs age-, BMI-, and health habit-matched non-DM controls (n=52) 1 Ryan et al ( 2003) P Value Rate of DM or IGT Diabetes Assessment Sample (N) Study
- 28. Diabetes, hyperglycaemia and diabetic ketoacidosis: case reports *Into widespread use DKA = diabetic ketoacidosis 1. Koller E et al. Am J Med 2001;111:716–723; 2. Koller E et al. Pharmacotherapy 2003;23:735–744 ; 3. Koller E et al. Pharmacotherapy 2002;22:841–852; 4. Koller E. et al. J Clin Psychiatry 2004;65:857–863. Year of introduction New cases Exacerbations DKA Deaths Clozapine 1 1990* 242 54 80 25 Olanzapine 3 1996 188 44 80 15 Quetiapine 4 1998 34 8 21 11 Risperidone 2 1993 78 46 26 4
- 29. Antipsychotic therapy and differential risk for hyperlipidaemia* *Adjusted for age, sex, duration of follow-up, use of -blocker, -blockers, corticosteroid, thiazide diuretic, lithium, valproate, oral contraceptives containing norgesterol. N = 18,309. Koro et al. Arch Gen Psychiatry . 2002;59:1021. Versus conventional antipsychotic agents Versus conventional antipsychotic agents Versus no exposure Versus no exposure Odds of hyperlipidemia Olanzapine users Risperidone users P 0.001 P 0.001 0 1 2 3 4 5 6 7 8 9 10
- 30. HOMA insulin resistance in treated patients with schizophrenia 0 1 2 3 4 5 6 Controls Typical Risperidone Olanzapine Clozapine HOMA = homeostasis model assessment Newcomer JW et al., Arch Gen Psychiatry , 2002;59:337–345. P < 0.05 P = 0.06 HOMA insulin resistance
- 31. ADA consensus on antipsychotic drugs and obesity and diabetes + = increased effect; - = no effect; D = discrepant results. *Newer drugs with limited long-term data. Precise risk estimates not ≤ available. † Not available in the UK American Diabetes Association. Diabetes Care. 2004;27(2):596–601 - - +/- ziprasidone* † - - +/- aripiprazole* D D + + quetiapine D D + + risperidone + + + + + olanzapine + + + + + clozapine Dyslipidaemia Diabetes Risk Weight Gain Drug
Editor's Notes
- This study was performed to evaluate the relationship between insulin-mediated glucose disposal and fat distribution in black males and females with type 2 diabetes. Female subjects had a substantially higher total fat volume than males, although abdominal fat volume did not differ between males and females. Despite these differences, glucose disposal decreased as the amount of adipose tissue increased, and this relationship was similar in males and females. The study concluded that abdominal fat, and not gender or subcutaneous fat, was the best predictor of impaired glucose regulation in this group of diabetics. It has been hypothesized that abdominal adipocytes may be more insulin-resistant than subcutaneous adipocytes and therefore more likely to generate free fatty acids. Banerji MA. Lebowitz J, Chaiken RL, Gordon D, Kral JG, Lebovitz HE. Relationship of visceral adipose tissue and glucose disposal is independent of sex in black NIDDM subjects. Am J Physiol Endocrinol Metab . 1997;273:E425-E432
- Many factors contribute to the increased risk for medical comorbidities in patients with schizophrenia or other mental illnesses. These are related to the illness itself, health behaviours, drug treatments and system of care. Psychiatrists do not always address the detection and treatment of physical illness in their patients. However, co-morbid conditions may adversely affect the treatment and clinical course of schizophrenia, hence it is important that these are considered as part of the management of patients. This slide summarizes the various sources of risks for medical comorbidities in patients with mental illness. 1 Increased risk for medical illness in people with major mental disorders may be related to the disease itself. The negative symptoms of schizophrenia, including loss of social skills, drive, and motivation, may place the patient at increased medical risk. In addition, ongoing psychiatric symptoms can make it difficult for patients to coherently communicate their medical needs. The incidence of illnesses such as diabetes may also be inherently higher among those with schizophrenia or bipolar disorder, placing the individual at greater risk of diabetes-related morbidity. An unhealthy lifestyle, which might include high-risk behaviours such as smoking, substance abuse, lack of exercise, and poor diet, can certainly contribute to medical risk in people with major mental disorders. Substance and alcohol abuse leading to intravenous drug use and unsafe sex may also contribute to the prevalence of HIV/AIDS and hepatitis C in these patients. Treatment-related comorbidity results primarily from the use of neuroleptic and anticholinergic medications. Side effects associated with antipsychotics include weight gain, diabetes, hyperlipidaemia and hyperprolactinaemia — all of which increase metabolic risk and cardiovascular disease. In addition, r esearch has shown that patients with schizophrenia may suffer a downward socioeconomic shift that adversely affects their access to healthcare. Infrastructural barriers in the health care system, combined with fragmentation of healthcare services, can also create impediments to good care for those with major mental disorders. 1. Lambert TJR, Velakoulis D, Pantelis C. Medical comorbidity in schizophrenia. Med J Aust. 2003;178:S67-S70.
- This slide illustrates the cumulative effect of risk factors and illustrates that risk factors are more than additive; the total risk is higher than just the sum of the individual risk factors. Monitoring of a USA population cohort in the town of Framingham, Massachusetts, USA, for the period of 12 years led to the identification of the major CVD risk factors, including high blood pressure, high total blood cholesterol, smoking, obesity and diabetes. Odds ratio for each of these risk factors alone ranges from around 1.2 to 2.2. When more than one factor is present, odds ratios are increased by more than an additive rate, so that all five (BMI>27, smoking, high total cholesterol, diabetes and hypertension) led to an approximate 7-fold increased risk compared to any one risk factor alone. 1. Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation . May 1998;97:1837 – 1847
- The major cardiovascular risk factors revealed in the Framingham study (obesity, smoking, diabetes and hypertension and dyslipidaemia) are those that, in the general population, are modifiable by behavioural changes and improved care. Individuals with schizophrenia are at increased risk for modifiable cardiovascular risk factors than the general population as shown in this slide. These risk factors are a major contributor to increased mortality in schizophrenia. The increased cardiovascular risks in the schizophrenic population highlights the need for intervention in this patient population to improve overall patient health. Although diabetes cannot be considered a modifiable risk factor, maintainence of good glycaemic control by can prevent the progression of the impaired fasting glucose to full blown diabetes. Allison DB et al . Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999,Nov;156(11):1686-1696. 2. Herran A et al. Determinants of smoking behaviour in outpatients with schizophrenia . Schizophr Res . 2000 Jan 21;41(2):373-381 ; 3. Goff DC, Cather C, Evins AE, Henderson DC, Freudenreich O, Copeland PM et al . Medical morbidity and mortality in schizophrenia: guidelines for psychiatrists. J Clin Psychiatry 2005;66:183-94. 4. Davidson S et al. Cardiovascular risk factors for people with mental illness. Aust N Z J Psychiatry . 2001 Apr;35(2):196-202. Dyslipidemia Hypertension Diabetes Smoking Obesity Modifiable risk factors ≥ 18% 10-14% 50-80% 45-55% Prevalence up to 5× 2× 2-3× 1.5-2× Relative risk
- This slide summarises the criteria for defining metabolic syndrome according to the National Cholesterol Education Program (NCEP). NCEP published their updated recommendations for cholesterol testing and management in The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III). 1. NCEP Expert Panel. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation . 2002;106(25):3143–3421
- This slide illustrates the pooled incidence of clinically significant weight gain reported in the US product labels for aripiprazole, risperidone, quetiapine, and olanzapine. All data were obtained in placebo-controlled trials, with clinically meaningful weight gain defined as ≥ 7% increase in body weight from baseline (about 10 pounds for a woman and 15 pounds for a man), which is considered by the National Institutes of Health to be the threshold for the development of serious adverse effects. As seen in this graph, compared with placebo, clinically significant weight gain occurred in 29% of the patients taking olanzapine, 1 23% taking quetiapine, 2 18% taking risperidone, 3 and 8% taking aripiprazole. 4 With long-term exposure to olanzapine (median 238 days), up to 56% of patients experienced clinically significant weight gain. 1 These data provide a guide to clinicians about what to expect when choosing an atypical antipsychotic in terms of relative weight gain and potentially weight-related metabolic disturbances. References: 1. Zyprexa ® [package insert]. Indianapolis, Ind: Eli Lilly and Company; 2004; 2. Seroquel ® [package insert]. Wilmington DE: AstraZenaca; 2004; 3. Risperdal ® [package insert]. Titiusville, NJ: Janssen Pharmaceutica Products, LP; 2003; 4. Abilify ® [package insert]. Princeton NJ: Bristol-Myers Squibb; Rockville, Md: Otsuka America Pharmaceutical; 2005.
- This was a double-blind, multi-center study to compare long-term weight effects of aripiprazole and olanzapine in patients with acute relapse of schizophrenia. Patients were randomized to aripiprazole (15-30 mg/day; n=154 ) or olanzapine (10-20 mg/day; n=156) for 26 weeks. Significant differences in mean weight change were observed throughout the study; at Week 26, there was a mean weight increase of 4.23 kg with olanzapine and a mean weight loss of 1.37 kg with aripiprazole ( P <0.001), a difference of 5.6 kg.
- This slide lists some of the studies that have demonstrated the higher prevalence of diabetes or impaired glucose tolerance in schizophrenia and bipolar disorder. In a 2003 study, Ryan et al demonstrated that first-episode, drug-naive patients with schizophrenia have impaired fasting glucose tolerance significantly more often than healthy control subjects (P< 0.02). 1 Dixon et al examined Medicare and Medicaid data from 1991, a time predating the widespread use of atypical antipsychotics. H igher rates of diabetes were seen for patients with schizophrenia than the general population. 2 The study by Lilliker (1980), conducted a decade before atypical antipsychotics came into existence, similarly observed that diabetes occurred more often in patients with bipolar disorder than in the general population. 1. Ryan MC, Collins P, Thakore JH. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry. 2003;160:284-289; 2. Dixon L, Weiden P, Delahanty J, et al. Prevalence and correlates of diabetes in national schizophrenia samples. Schizophr Bull. 2000;26:903-912; 3. Lilliker SL. Prevalence of diabetes in a manic-depressive population. Compr Psychiatry. 1980;21:270-275.
- Despite the limitations of database analyses, further evidence from case reports supports the link between some atypical antipsychotic and diabetes. This slide shows data from the FDA MedWatch Drug Surveillance System together with published reports and meetings abstracts that were used to identify reports of diabetes or hyperglycemia associated with each of the treatments. Analysis of cases identified from the FDA MedWatch system provides support for an association between clozapine and olanzapine therapy and diabetes development. 1. Koller E et al. C lozapine-associated diabetes. Am J Med 2001;111:716–723; 2. Koller E et al. Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy 2003;23:735-744; 3. Koller E et al. Olanzapine-associated diabetes mellitus. Pharmacotherapy 2002;22:841–852; 4. Koller E. et al. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus .J Clin Psychiatry 2004;65:857-863.