Physical illness in patients with severe mental disorders. II. Barriers to care, monitoring and treatment guidelines, plus recommendations at the system and individual level
Authors: MARC DE HERT, DAN COHEN, JULIO BOBES, MARCELO CETKOVICH‐BAKMAS, STEFAN LEUCHT, DAVID M. NDETEI, JOHN W. NEWCOMER, RICHARD UWAKWE, ITSUO ASAI, HANS‐JURGEN MÖLLER, SHIV GAUTAM, JOHAN DETRAUX, CHRISTOPH U. CORRELL
Journal: World Psychiatry (2011)

As outlined in the first part of this bi-partite publication 1, individuals with severe mental illness (SMI) are at an increased risk for a large number of physical disorders that require clinical attention. People with SMI are entitled to the same standards of care as the rest of the population. However, rates of undiagnosed and untreated medical illnesses are higher in SMI individuals, compared to the general population. Despite the fact that the higher morbidity and mortality of physical illnesses in SMI patients are largely due to modifiable lifestyle risk factors 1, there is sufficient evidence that disparities not only in health care access and utilization, but also in health care provision, contribute to these poor physical health outcomes 2,3. According to one recent study, people with psychotic disorders, bipolar disorder, or major depressive disorder have greatly increased odds of reporting difficulties in accessing care (odds ratios, OR=2.5–7.0) 4. Although parity in access to and provision of health care should be conceived as a basic human right, a confluence of patient, provider, treatment and system factors has created a situation in which access to and quality of health care is problematic for individuals with SMI 5. Table 1 summarizes the barriers to the recognition and management of somatic illnesses in SMI patients. In many cases, the SMI patients' only contact with the health service is through the mental health care team. Moreover, because of their SMI, these patients are less capable than other patients of interpreting physical signs, as well as solving their problems and caring for themselves, which places an increased responsibility on the part of mental care workers to be in the fore front for the physical health care of these patients 6. Two consensus conferences have called on mental health care providers to take responsibility for the physical health of their patients 7,8. However, despite data suggesting that the sensitization of psychiatrists to expand their tasks to include assessments of both mental and physical health in SMI patients can be improved by consensus guidelines 9, many psychiatrists still consider their primary or, even, sole function to provide clinical care in terms of psychiatric symptom control and are reluctant to monitor physical health 6. Although many barriers can be related to the patient and his/her illness, and/or to the clinician and his/her medical treatment, the reintegration of psychiatric care and general somatic services, with an ultimate goal of providing optimal services to this vulnerable patient population, seems to represent one of the most important challenges for psychiatric care today 7,10. However, this is only one part of the broader picture: 37% of 195 countries in the world do not even have a specified budget for mental health, and 25% of the countries (of the 101 countries that reported their mental health budget) spend less than 1% of their total health care budget on mental health 11. In some parts of the world, mental health resources are even poorer. In Africa and in the Western Pacific Regions, a mental health policy was found to be present in only half of the countries 12. Moreover, in developing as well as in developed countries, stigmatization, discrimination, erroneous beliefs and negative attitudes associated with SMI will have to be eliminated to achieve parity in health care access and provision. Due to differences between regions and countries (e.g., level of economic development, budgeting of health care, availability of mental health care personnel, etc.), the majority of actions should be adapted to the local needs and circumstances 7. The excess mortality rates in persons with SMI are largely due to modifiable health risk factors 1. Therefore, the monitoring and treatment of these factors should be a part of clinical routine care of the psychiatrist. Furthermore, to address the problem of suboptimal medical treatment for patients with SMI, changes need to be made in the health care system and delivery 48, wherein the psychiatrist, once again, can and should play a pivotal role. Physical health checks should focus on monitoring 49,50,51: - weight gain and obesity (body mass index, BMI; waist circumference, WC); - blood pressure; - dietary intake; - activity level and exercise; - use of tobacco and alcohol or other substances; - fasting blood levels of glucose; - fasting blood levels of lipids, especially triglycerides and high-density lipoprotein (HDL)-cholesterol; - prolactin levels (if indicated by reproductive system and/or sexual symptoms); - cardiovascular disease (CVD) risk and electrocardiographic (ECG) parameters; - dental health; - liver function tests, blood count, thyroid hormone, electrolytes (periodically, as indicated). Many of these physical health monitoring tests are simple, easy to perform and inexpensive 6,52,53,54, and therefore can/should be implemented in the health care systems of developed as well as developing countries. Moreover, even in developing countries, several of these simple and inexpensive measurements (e.g., body weight and blood pressure) can be routinely done by health workers other than doctors. Screening and assessment of physical health should begin with the patient's personal and family history, covering 40: diabetes mellitus (DM), hypertension, CVD (myocardial infarction or cerebrovascular accident, including age at onset), smoking, diet, physical activity. Secondly, as the individual components of the metabolic syndrome (MetS) (see 1) are critical in predicting the morbidity and mortality of CVD, DM, cancer and other related diseases, these, as well as some other non-metabolic parameters, should be checked at baseline and measured regularly thereafter 46,51. Concerning metabolic parameters, one should remember that drug-naïve, first-episode patients, as well as children and adolescents with psychotic disorders, are at higher risk for metabolic side effects of medications 55,56. Higher baseline values of weight and visceral fat distribution, as well as laboratory evidence of impaired glucose and lipid metabolism, have been, although not consistently, reported for these patients 57. Likewise, young drug-naïve patients of non-Caucasian ethnicity with a personal or family history of metabolic risk factors are more likely to develop metabolic side effects 57. Psychiatrists should, regardless of the medication prescribed, monitor and chart BMI and WC of every patient with SMI at every visit, and should encourage patients to monitor and chart their own weight 58. WC seems to be a more useful measurement than BMI. Prospective data in patients with impaired glucose tolerance revealed that central adiposity, having a strong correlation with insulin resistance 59, better predicted future type 2 DM than BMI 60. WC is also a stronger indicator than BMI for systolic blood pressure, HDL-cholesterol, or triglycerides 61, and has been proposed as the best single measure to identify individuals at high risk for CVD and the MetS 52. It is also a simple tool to assess the likelihood of insulin resistance: in one study, a WC <100 cm excluded insulin resistance in 98% of males and 94% of females 61. This assessment can easily be done with a simple and inexpensive waist tape measure. The International Diabetes Federation (IDF) definition (see 1) provides sex- and race-specific criteria for defining elevated WC to identify people with central obesity, thus adapting this criterion to make it also applicable to non-Caucasian populations. However, multiple studies found that WC is rarely measured 62,63,64. The other MetS criteria of blood pressure, fasting plasma glucose and fasting lipid profile should also be assessed, even if WC is normal. As the MetS components seem to cluster, the presence of one component often suggests the presence of the others. High blood pressure in SMI patients is often missed 65. As the cost for measuring blood pressure is low, and hypertension is a relevant CVD risk factor, blood pressure can/ought to be assessed routinely, even at every visit. Hypertension can be defined as a systolic blood pressure $130 mm Hg or a diastolic blood pressure $85 mm Hg 66. This diagnosis requires at least two separate, independent measurements that fall both within the range of hypertension 65. Individuals with a systolic blood pressure of 120 to 130 mm Hg or a diastolic blood pressure of 80 to 85 mm Hg should be considered as pre-hypertensive and require lifestyle modifications to prevent heart disease 67. A baseline measure of plasma glucose level should be collected for all patients before starting treatment 58. In patients starting antipsychotic (AP) treatment, finger prick tests should be carried out at baseline, 6 and 12 weeks to capture early cases of hyperglycemia and then, at minimum, yearly. Formal laboratory screening tests can then be carried out when necessary 68. Ideally, blood glucose measurement should be conducted in the fasting state, because this is the most sensitive measurement for the detection of developing glucose abnormalities. However, this can prove problematic to achieve. In cases where patients present non-fasting, it is preferable to conduct a random blood glucose test (and/or hemoglobin A1C test), rather than to miss the opportunity to screen 6. An abnormal test value (fasting plasma glucose ≥126 mg/dl or hemoglobin A1C value ≥6.5%) 69 suggests the possibility of DM. Fasting plasma glucose levels between 100 and 125 mg/dl (or hemoglobin A1C values of 5.7–6.4%) are indicative of pre-diabetes and should also prompt closer assessment and follow-up. However, the possibility of false positive results need to be excluded by at least one repeated measurement of fasting plasma glucose. If the abnormality is confirmed, the frequency of fasting plasma glucose measurements needs to be increased to 4 times a year to assess the speed of the rise. Likewise, if fasting plasma glucose levels are ≥126 mg/dl or hemoglobin A1C values are >6.4%, the possibility of false positive results needs to be excluded by at least one repeated measurement of fasting plasma glucose. If the second measurement confirms the abnormality, this should lead to a consultation with an internist or other primary health care provider for further assessment and, possibly, treatment. Importantly, hemoglobin A1C reflects the mean glucose levels during the past 3 months. This is excellent as a goal for treatment outcome, but probably not sensitive enough to detect hyperglycaemia in its early stages 70. Patients who have significant risk factors for DM (family history, BMI ≥25, WC above critical values, gestational diabetes, minority ethnicity) should have their fasting plasma glucose level or hemoglobin A1C value monitored at the same time points as other patients starting medication (baseline, week 6 and 12), but thereafter they need to be checked more frequently (approximately every 3–6 months). Patients who are gaining 7% or more of their baseline weight should also have their fasting plasma glucose level or hemoglobin A1C value monitored more frequently, for example, every 4 months 58. Because of its high mortality, special attention should be given to diabetic ketoacidosis (DKA). DKA signs and symptoms often develop quickly, sometimes within 24 hours. One may notice: polyuria and polydipsia, nausea and vomiting, abdominal pain, poor appetite, unintended weight loss, fatigue, Kussmaul respirations (a pattern of deep breathing and hyperventilation in response to metabolic acidosis), fruity-scented breath, somnolence and confusion. The presentation of a patient with DKA varies substantially depending on the severity of the episode (e.g., mild or moderately ill patients may only describe vague symptoms of fatigue, lethargy, poor appetite, or headache). In type 2 DM, polyuria and polydipsia may have been building for weeks to months. More specific signs of DKA, which can be detected through laboratory tests, include: blood glucose level >250 mg/dL, pH <7.3 and a moderate degree of ketonemia or ketonuria 71,72,73,74. Lipid parameters (especially triglycerides and HDL-cholesterol) should also be assessed at baseline and at 3 months, with 12-monthly assessments thereafter. More frequent screening is unnecessary, unless in case of abnormal values. Abnormal values for total cholesterol are >190 mg/dl for patients without DM and >175 mg/dl for patients with DM. Abnormal low-density lipoprotein (LDL)-cholesterol values for patients without and with DM are >115 mg/dl and >100 mg/dl, respectively 65. However, the cost and lack of availability of this assessment may not make it feasible as a routine measure in all settings and patients. The patient's individual CVD risk should be calculated from his/her age, sex, presence or absence of DM, smoking habit, systolic blood pressure and total cholesterol, or the ratio of total cholesterol to HDL-cholesterol with reference to published guidelines, local protocols or online risk calculators. These measurements are relatively simple and easily accessible 54. In the psychiatric setting, it is often difficult to obtain an ECG as rapidly as in other acute medical settings. In less well economically developed countries, obtaining an ECG may be even more problematic. In these cases, whatever psychotropic a psychiatrist is intending to prescribe, patients should be asked about heart risks, such as family history of early cardiac death (i.e, <50 years in males and <55 years in females), personal history of a heart murmur, previous prescription of cardiac medications or anti-hypertensives, or if he/she has ever had an episode of simple syncope 51. Nevertheless, the measurement of ECG parameters as a baseline requirement deserves serious consideration. We propose that the ECG monitoring of patients with SMI has to be seen as a desired baseline parameter in order to assess the overall cardiac health status. As a general rule, we recommend that every patient should have an ECG measurement prior to the initiation of medication. Thereafter, depending on the advice given by a cardiologist, ECG monitoring can be repeated. A baseline ECG assessment is especially important in patients with clinical risk factors for arrhythmias, i.e., those with a family history of early cardiac death, personal history of a heart murmur, hypertension or diabetes, tachycardia at rest, irregular heart beats and fainting spells, particularly upon exertion. If possible, to have a reference value, prolactin levels should be measured in all patients at baseline. If too expensive, prolactin levels should only be measured in case sexual or reproductive system abnormalities are reported. Yet, these need to be asked about directly and monitored. Reproductive system abnormalities triggering prolactin level measurement include amenorrhea or oligomenorrhea (i.e, <9 periods per year), galactorrhea, gynecomastia in males, and/or breast tenderness and pain in females. Sexual dysfunction that should prompt prolactin measurement include new symptoms and/or those that coincided with antipsychotic treatment or dose change, including decreased libido, erectile or ejaculatory dysfunction, problems with arousal or orgasm. In these cases, prolactin should be measured every 3 months, especially when increasing the dose of known prolactin-elevating compounds. Although the clinician needs to be aware that laboratory ranges may differ between sites 75,76, in most laboratories normal prolactin values are set at 20 ng/ml (424 mIU/mL) for men and 25 ng/ml (530 mIU/L) for women 77. A complicating factor during measurement of prolactin levels is the presence of macroprolactin, which is essentially biologically inactive, but may lead to falsely high prolactin levels as measured by many assays 78. Conservative estimates suggest that the presence of macroprolactin leads to misdiagnosis in as many as 10% of all reported instances of biochemical hyperprolactinemia 79. In cases where measured prolactin is significantly raised, reporting of estimated monomeric prolactin instead of just "macroprolactin positive" can avoid unnecessary investigations. With antipsychotic treatment, prolactin levels below 200 ng/ml and, mostly, below 100 ng/ml are most commonly observed. To date, the physiological relevance of these levels is unknown, unless hypogonadism (i.e., a state of markedly reduced sex hormone production) is the result, which has been associated with osteoporosis and fracture risk. The risk for breast cancer is much less clear. What seems to be certain is that any prolactin level that leads to hypogonadism should prompt a treatment change to a less prolactin elevating antipsychotic (e.g., quetiapine, aripiprazole or, in refractory patients, clozapine). Magnetic resonance imaging (MRI) of the sella turcica to rule out a prolactinoma should only be ordered after other reasons for prolactin elevation are excluded (e.g., chronic renal failure by assessing creatinine, hypothyroidism by assessing thyroid stimulating hormone, and pregnancy or oral contraception), if prolactin levels are above 200 ng/ml and do not decrease after a change to a lower risk agent, or if lateral visual deficits are observed, raising the suspicion of a prolactinoma 80. Although currently considered by many clinicians as not important, oral health needs to be scrutinized in the same way as other physical health problems 81,82. Risk factors for a poor oral health (e.g., smoking, medication side effects) and individual oral care needs should be assessed 83. Physical screening and monitoring programs are well accepted by patients and can be implemented in a variety of settings. Contrary to general belief, it is not difficult to motivate most patients to take part in the fasting blood assessments, and most are keen to getting and discussing the results of the evaluations 53,54. Screening patients using an algorithm 84, monitoring form 85 or risk chart 65,86 is a simpler option than using the more complex and detailed guidelines previously published. Although, over recent years, both national and international groups have developed screening and monitoring guidelines 58,84,87,88,89,90,91,92,93,94,95, these seem not to be routinely implemented in the clinical care of patients 62,64,96,97. Follow-up monitoring should be done at appropriate intervals 98 (Table 2). Physical health assessments should be recorded on charts showing the times and results of the assessments compared with reference ranges 54. During initial phases of treatment, it is important to measure weight weekly to identify patients who gain weight rapidly. Waterreus and Laugharne 84 advocate screening of all patients on any medication at baseline (to identify high-risk individuals and to ensure early detection of changes in metabolic parameters), and, at the minimum, every 3 months. Other guidelines propose screening and monitoring at baseline, 3 months, 12 months and annually, unless patients gain at least 7% of baseline body weight or are at increased risk for adverse health outcomes (e.g., family history of DM or early cardiac death, personal history of overweight or obesity, gestational DM, minority ethnicity, etc.). If the patient has central obesity, hypertensive blood pressure (≥130/85 mm Hg), pre-diabetes (fasting plasma glucose =100–125 mg/dL or hemoglobin A1C =5.7–6.4%) or DM (fasting plasma glucose ≥126 mg/dL or hemoglobin A1C >6.4%), or marked dyslipidemia (total cholesterol >350 mg/dL; LDL-cholesterol >160 mg/dL; triglycerides >300 mg/dL), he/she should be referred to primary care provider to treat these conditions, unless simple healthy lifestyle guidance or behavioural adjustment and/or switching to a lower cardiometabolic risk medication can address these medical conditions adequately 17,99. Many, but not all, individuals with SMI either are unaware of the need to change or do not possess the knowledge and skills required to make lifestyle changes. Psychiatrists, physicians, nurses and other members of the multidisciplinary team can help educate and motivate people with SMI to address their lifestyle, including smoking, diet and exercise, through the use of effective behavioural interventions 57,100. Patients with SMI, as well as their family and caregivers, should be taught about healthy lifestyles and should receive psychoeducational packages to facilitate them. Psychoeducation does not need to be administered by a specialist (e.g., a nutritionist), nor does it require special training, but should be administered by staff at the mental health clinic. Lifestyle advice and interventions can be obtained using resources already available within the local mainstream service 6. Patients should be provided positive feedback and support 17 and treatment must be tailored to meet the individual needs of SMI patients 14. Non-pharmacological interventions, incorporating dietary and physical activity modifications, demonstrated promise in terms of preventing weight gain in schizophrenia 94,95,96,97,98,99,100,101,102,103. The impact on one's overall health, even with simple life style changes, is considerable (Table 3). A healthy diet, regular physical activity and quitting smoking are the key components of lowering the prevalence and impact of modifiable risk factors. However, if lifestyle interventions do not succeed, medication, including statins, anti-hypertensive therapy or antidiabetic agents, may be indicated. These drugs should be prescribed and managed as for the general population and are generally well tolerated 109,110. Moreover, pharmacologic treatments added to reduce antipsychotic-related weight can be tried. To date, most evidence exists for metformin (500 to 1000 mg bid with meals) or topiramate (50–200 mg in divided doses) 111. Many patients with SMI do not know the components of a healthy diet 46. It is commonly known that patients with schizophrenia have a diet higher in fat 111, higher in refined sugar 112, lower in fiber 25, and poor in fruits and vegetables 113. Therefore, nutrition education may be beneficial 46. Patients should be advised to avoid juices and soft drinks containing sugar and, even, artificial sweeteners, as well as high calorie, high fat, and nutritionally poor food, such as fast food and unhealthy snacks. The importance of consuming healthy alternatives, such as fresh fruit and vegetables, fish, and lean meats in a balanced way, should be stressed by clinicians whenever possible. Although educating patients (as well as their family and caregivers) about healthy food is recommended, patients need to understand that lifestyle changes should be gradual. Most people who experience rapid weight loss without gradual behaviour modifications will return to their previous weight. Losing weight hastily increases the likelihood of developing cholesterol gallstones. Further, many toxins are stored in fat tissue and a rapid weight loss may release those toxins too quickly 46. Changes in dietary composition can have substantial effects. Weight loss has many health-related benefits that are of particular importance to SMI patients, including a reduction in risk of DM and CVD, reduction of serum triglycerides and LDL-cholesterol concentrations, increase in HDL-cholesterol concentrations, and reduction in blood glucose concentrations and hemoglobin A1c among patients with type 2 DM. However, interventions that address nutrition, weight management and physical activity have not become a routine part of psychiatric care 98. The psychiatrist can involve the individual with SMI in educational and psychosocial programs that address the issues of health and wellness, which can reduce medical comorbidities in this population. These programs, such as "The Healthy Living" program, the "Small Changes" strategy and the "Solutions for Wellness" program have been shown to be effective in people with SMI 114,115,116,117,118,119. Table 4 gives some examples of behavioural interventions to improve the health of patients with SMI. Physical inactivity is one of the risk factors that theoretically can most easily be addressed and modified in individuals with SMI 100. People with schizophrenia are significantly more sedentary than the general population 120. Only 25.7% of these patients meet the minimum public health recommendation of 150 min a week of at least moderate-intensity physical activity 121,122. According to the guidelines of the American College of Sports Medicine and the American Heart Association, moderate-intensity physical activity between 150 and 250 min a week will provide modest weight loss and is effective in preventing weight gain. Greater amounts of physical activity (>250 min a week) can be associated with clinically significant weight loss 108. Physical activity can improve metabolic health status even in the absence of weight loss. There is evidence that physical activity with or without diet counselling is feasible and effective in reducing weight and improving cardiometabolic risk profile in people with schizophrenia 123. However, in patients who are obese, physical exercise should be accompanied by proper diet to achieve significant weight loss. For example, if a patient walks for 1 hour per day, about 200 calories are burned. While this is beneficial in terms of cardiovascular health, this energy expenditure will not result in substantial weight loss. More strenuous physical activities, such as jogging, may be necessary 46. Considering all these facts, patients should be advised to engage in at least 30 minutes of moderately vigorous activity (at least a brisk walk) on most days of the week 65. A meta-analysis of worldwide studies demonstrated that schizophrenic patients, compared with the general population, have a higher prevalence of ever smoking, heavy smoking and high nicotine dependence, as well as of risk factors that make them more vulnerable to start smoking 124. Up to 85% of individuals with SMI will die and/or have a reduced quality of life because of a tobacco-related disease 48,125. Cessation of smoking is associated with approximately a 50% decrease in the risk of coronary heart disease 104, and a 75% decrease in the risk of high/very high 10-year cardiovascular events 126. Therefore, SMI patients should be strongly encouraged to stop smoking. However, smoking cessation has important implications for the management of patients taking clozapine and olanzapine. Abrupt cessation of smoking is associated with a potentially serious risk of toxicity in patients taking clozapine, while olanzapine levels can also increase significantly. Cormac et al 127 found that the percentage of patients with a plasma clozapine level ≥1000 µg/l increased from 4.2% to 41.7% within the six month period following the smoking ban despite dose reductions. Therefore, plasma clozapine levels must be monitored closely and adjustments made in dosage, if necessary, for at least six months after cessation 127. Moreover, smoking cessation also increases the short-term risk for DM. In a prospective study, adults who quit smoking experienced an increased risk for incident DM that peaked within 3 years of quitting (hazard ratio, HR=1.91) but was still observable 6 years after quitting. The increased risk seems to be partially mediated by weight gain: withdrawal of nicotine may lead to increased appetite and excess caloric intake. Therefore, clinicians should consider countermeasures (e.g., use of nicotine replacement therapy), especially for heavy smokers 128. Treating tobacco dependence is effective in patients with SMI. There is emerging evidence that people with SMI can stop smoking 129,130,131,132. Moreover, treatments that work in the general population appear to be approximately equally effective in SMI patients. The evidence also suggests that treating tobacco dependence in SMI patients with stable psychiatric conditions does not worsen mental state 133. Finally, although staff from psychiatric hospitals often express concerns that adopting a smoke-free policy would have a negative impact on the hospital's treatment milieu, this is not necessarily the case 134. Therefore, at a minimum, psychiatric professionals should assess tobacco use in all patients, advise all tobacco users to quit, assist patients in developing a quit plan, and arrange follow-up 100. If necessary and possible, patients can be referred to a smoking cessation service, which can offer behavioural counselling, nicotine replacement therapy or other pharmacological interventions 65. Target blood pressure levels of less than 130/85 mmHg are recommended. Lifestyle changes, such as stopping smoking, reducing salt intake, weight reduction and increased exercise, may be sufficient to reduce mildly elevated blood pressure, although some patients are likely to require pharmacological therapy 65. Recently updated European guidelines stress the importance of choosing anti-hypertensive agents best suited to the individual patient's needs 86,135. Oral health advice, support and education should be provided to SMI patients, appropriate to their needs. Preventive and treatment programmes need to be tailored to meet the individual needs of patients with different diagnoses, severity and stages of mental illness. These should include dietary issues, smoking, and oral side effects of medication, namely dry mouth and carbohydrate craving. Advice on the dietary control of sugars and the importance of sugar free lubrication to relieve the symptoms of a dry mouth are essential to reduce the adverse oral side effects of some psychotropic drugs. Psychiatrists should be made more aware of the importance of oral health habits. Therefore, training for clinicians in the identification of oral health risk factors such as smoking and of oral side effects of medication, and on proper oral hygiene techniques, is necessary 83. Above all, patients with SMI need encourageme