systematic review on excess rates of physical illness in schizophrenia stefan leucht, md department...
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Systematic Review on Excess Rates of Physical Illness in Schizophrenia
Stefan Leucht, MD Stefan Leucht, MD Department of Psychiatry and Psychotherapy, TU-Munich, GermanyDepartment of Psychiatry and Psychotherapy, TU-Munich, Germany
Programme on the physical health of people with mental disordersProgramme on the physical health of people with mental disorders
Published in: Published in: Leucht S, Burkard T, Henderson J, Maj M, Sartorius N. Physical Leucht S, Burkard T, Henderson J, Maj M, Sartorius N. Physical illness and schizophrenia: a review of the literature.illness and schizophrenia: a review of the literature.
Acta Psychiatr Scand. 2007 Nov;116(5):317-33 Acta Psychiatr Scand. 2007 Nov;116(5):317-33
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Increased Mortality Rates for Medical Disorders in schizophrenia
50% increased risk of death from medical causes in schizophrenia, and 20% shorter lifespan(Harris et al. Br J Psychiatry 1998;173:11)
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Method
MEDLINE search (1966 – 2006) combining the MESH term of schizophrenia with the MEDLINE search (1966 – 2006) combining the MESH term of schizophrenia with the general MESH terms of physical illnesses:general MESH terms of physical illnesses:
Bacterial Infections and Mycoses [C01] +Bacterial Infections and Mycoses [C01] +
Virus Diseases [C02] + Virus Diseases [C02] +
Parasitic Diseases [C03] + Parasitic Diseases [C03] +
Neoplasms [C04] + Neoplasms [C04] +
Musculoskeletal Diseases [C05] + Musculoskeletal Diseases [C05] +
Digestive System Diseases [C06] + Digestive System Diseases [C06] +
Stomatognathic Diseases [C07] + Stomatognathic Diseases [C07] +
Otorhinolaryngologic Diseases [C09] + Otorhinolaryngologic Diseases [C09] +
Nervous System Diseases [C10]Nervous System Diseases [C10]
Eye Diseases [C11]Eye Diseases [C11]
Urologic and Male Genital Diseases [C12] Urologic and Male Genital Diseases [C12]
Female Genital Diseases and Pregnancy Complications [C13]Female Genital Diseases and Pregnancy Complications [C13]
4
Method
Cardiovascular Diseases [C14]Cardiovascular Diseases [C14]
Hemic and Lymphatic Diseases [C15] Hemic and Lymphatic Diseases [C15]
Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
Skin and Connective Tissue Diseases [C17]Skin and Connective Tissue Diseases [C17]
Nutritional and Metabolic Diseases [C18]Nutritional and Metabolic Diseases [C18]
Endocrine System Diseases [C19]Endocrine System Diseases [C19]
Immune System Diseases [C20]Immune System Diseases [C20]
Disorders of Environmental Origin [C21]Disorders of Environmental Origin [C21]
Animal Diseases [C22]Animal Diseases [C22]
Pathological Conditions, Signs and Symptoms [C23] + Pathological Conditions, Signs and Symptoms [C23] +
44202 44202 hits!hits!
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Bacterial Infections and Mycoses, Viral Diseases, Parasitic Diseases
Bacterial infections and mycoses
Surprisingly little (a few studies on tuberculosis)
Viral diseases
1. HIV (~20 studies), Hepatitis B and C
Mostly USA east coast cities, very high prevalence rates, but
broad range (1.3-22.9%), no population-based studies
Paradox—reduced sexual interest—high rates of HIV
Epidemiological studies of better methodology still warranted
2. Bornavirus, influenza virus (etiological studies)
Parasitic diseases Toxoplasma gondii, 21 reportsMainly increased T gondii antibody titers in schizophrenia
7
NeoplasmsProbably the best studied area with a number of population based studies available Probably the best studied area with a number of population based studies available (n=13), many more studies of less good quality (first one 1909)(n=13), many more studies of less good quality (first one 1909)
Most of the studies show decreased rates of cancer in people with schizophreniaMost of the studies show decreased rates of cancer in people with schizophrenia
Only the largest one, a Finnish population based studies showed increased rates, Only the largest one, a Finnish population based studies showed increased rates, reasons are unclear, therefore despite the enormous amount of studies the puzzle reasons are unclear, therefore despite the enormous amount of studies the puzzle has not been put together yet.has not been put together yet.
Specific kinds of cancer different results, e.g. lung cancer in large Danish studies Specific kinds of cancer different results, e.g. lung cancer in large Danish studies decreased, but in Finnish or recent Israeli study increaseddecreased, but in Finnish or recent Israeli study increased
Hypotheses explaining decreased risk:Hypotheses explaining decreased risk: medication, early Danish studies say that medication, early Danish studies say that smoking was not allowed in psychiatric hospitals, discussion on genetic factors that smoking was not allowed in psychiatric hospitals, discussion on genetic factors that are associated with the development of schizophrenia on the one hand and are associated with the development of schizophrenia on the one hand and protection against cancer on the other hand.protection against cancer on the other hand.
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Musculoskeletal DiseasesRheumatoid Arthritis:Rheumatoid Arthritis: 19 studies, almost all show reduced rates of RA in 19 studies, almost all show reduced rates of RA in schizophreniaschizophrenia
Hypotheses: institutionalization, immobility, less active life, antinflammatory effects Hypotheses: institutionalization, immobility, less active life, antinflammatory effects of antipsychotic drugs, immunsystem related factors of antipsychotic drugs, immunsystem related factors -methodological artefact: Mors et al. 1999 population based not only decreased methodological artefact: Mors et al. 1999 population based not only decreased rates of osteoarthritis, but also of arthrosis and unspecific back pain. Artefact of rates of osteoarthritis, but also of arthrosis and unspecific back pain. Artefact of underreporting by people with schizophrenia (e.g. because of decreased pain underreporting by people with schizophrenia (e.g. because of decreased pain sensitivity).sensitivity).
Osteoporosis:Osteoporosis: 13 studies. Quality of most of the studies is limited, especially large 13 studies. Quality of most of the studies is limited, especially large population based studies are not available. However, almost all show reduced bone population based studies are not available. However, almost all show reduced bone mineral densitiy in people with schizophrenia.mineral densitiy in people with schizophrenia.
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Digestive System Diseases, Nutritional and Metabolic Diseases Endocrine System Diseases
Weight gain, diabetes, metabolic syndrome:Weight gain, diabetes, metabolic syndrome:
Many studies on the effects of the new generation antipsychoticsMany studies on the effects of the new generation antipsychotics
Given that this question is a hot topic, relatively few high quality studies on pure Given that this question is a hot topic, relatively few high quality studies on pure epidemiology were found.epidemiology were found.
Epidemiology is not clear, most studies show increased BMI and higher rates of Epidemiology is not clear, most studies show increased BMI and higher rates of diabetes of people with schizophrenia compared to normal controls. More studies are diabetes of people with schizophrenia compared to normal controls. More studies are needed, especially studies outside the US.needed, especially studies outside the US.
Increased rates of overweight were already found in the preatypical area.Increased rates of overweight were already found in the preatypical area.
Hypotheses:Hypotheses: medication, some small not very convincing studies that increased rates medication, some small not very convincing studies that increased rates even in antipsychotic naïve patients, life-style (little exercise, poor quality of food – little even in antipsychotic naïve patients, life-style (little exercise, poor quality of food – little evidence available) evidence available)
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Prevalence of overweight in US adults
1. Behvioral Risk Factor Surveillance System (BRFSS, * BMI >30)
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Only in America... Only in America...
12
ClozapineClozapine
OlanzapineOlanzapine
ThioridazineThioridazine
SertindoleSertindole
ChlorpromazineChlorpromazine
RisperidoneRisperidone
HaloperidolHaloperidol
FluphenazineFluphenazine
ZiprasidoneZiprasidone
AmisulprideAmisulpride
00 11 22 33 44 55
Weight gain in kgWeight gain in kg
4.454.45
4.154.15
3.193.19
2.922.92
2.582.58
2.12.1
1.081.08
0.3740.374
0.040.04
0.80.8 Aripiprazol 0,6kg within 4 weeksAripiprazol 0,6kg within 4 weeks
Meta-analysis of weight gain liabilities
Allison et al., J Clin Psychiatry 2001; 62 (suppl 7):22-31
4 – 10 week studies, N=72
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Digestive System Diseases, Nutritional and Metabolic Diseases Endocrine System Diseases
Weight gain, diabetes, metabolic syndrome:Weight gain, diabetes, metabolic syndrome:
Many studies on the effects of the new generation antipsychoticsMany studies on the effects of the new generation antipsychotics
Given that this question is a hot topic, relatively few studies on pure epidemiology were Given that this question is a hot topic, relatively few studies on pure epidemiology were found and even fewer studies with high quality.found and even fewer studies with high quality.
Epidemiology is not clear, most studies show increased BMI and higher rates of Epidemiology is not clear, most studies show increased BMI and higher rates of diabetes of people with schizophrenia compared to normal controls. More studies are diabetes of people with schizophrenia compared to normal controls. More studies are needed, especially studies outside the US.needed, especially studies outside the US.
Increased rates of overweight were already found in the preatypical area.Increased rates of overweight were already found in the preatypical area.
Hypotheses:Hypotheses: medication, some small not very convincing studies that increased rates medication, some small not very convincing studies that increased rates even in antipsychotic naïve patients, life-style (little exercise, poor quality of food – little even in antipsychotic naïve patients, life-style (little exercise, poor quality of food – little evidence available) evidence available)
14 Allison DB et al. J Clin Psychiatry. 1999;60:215-220.
Percent
< 18.518.5-20 20-22 22-24 24-26 26-28 28-30 30-32 32-34 > 34
0
10
20
30
No schizophrenia
Schizophrenia
Obese Overweight Acceptable Under-weight
BMI Range
BMI Distributions for General Population and Those With Schizophrenia (1989)
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Schizophrenia: Natural Causes of Death
Higher standardized mortality rates (SMR) for men than the general Higher standardized mortality rates (SMR) for men than the general population frompopulation from11:: Diabetes Diabetes 2.7 2.7 × × general populationgeneral population Cardiovascular disease (CVD)Cardiovascular disease (CVD) 2.3 2.3 ×× general population general population Respiratory diseaseRespiratory disease 3.2 3.2 ×× general population general population Infectious diseases Infectious diseases 3.4 3.4 ×× general population general population
The largest single cause of death in schizophrenic patients is CVD, The largest single cause of death in schizophrenic patients is CVD, despite it not having the largest mortality ratio compared with the despite it not having the largest mortality ratio compared with the general populationgeneral population11
That is because a much larger That is because a much larger numbernumber of people of people overall die from CVDoverall die from CVD22
1. Harris EC, Barraclough B. Br J Psychiatry. 1998;173:11-53. 2. Hennekens et al. 2005
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Digestive System Diseases, Nutritional and Metabolic Diseases Endocrine System Diseases
Polydipsia:Polydipsia:
Surprisingly large literature (14 studies) showing quite clearly increased rates of Surprisingly large literature (14 studies) showing quite clearly increased rates of polydipsia in schizophrenia (reviewed e.g. by Leon et al. 1994)polydipsia in schizophrenia (reviewed e.g. by Leon et al. 1994)
Suggesting that this phenomenon is present in more than 20% of chronic Suggesting that this phenomenon is present in more than 20% of chronic psychiatric patientspsychiatric patients
Not considered enough by psychiatrists, although consequences can be fatal Not considered enough by psychiatrists, although consequences can be fatal (delirium, water intoxication, death)(delirium, water intoxication, death)
The problem is that most studies used rather soft definitions to define polydipsia, The problem is that most studies used rather soft definitions to define polydipsia, e.g. just simple hyponatremia. How often dangerous polydipsia occurs is not clear e.g. just simple hyponatremia. How often dangerous polydipsia occurs is not clear (case reports exist).(case reports exist).
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Digestive System Diseases, Nutritional and Metabolic Diseases Endocrine System Diseases
Thyroid dysfunction:Thyroid dysfunction:
There is a large spectrum of thyroid function test abnormalities in schizophrenia and in There is a large spectrum of thyroid function test abnormalities in schizophrenia and in psychiatric patients in general, although the alterations have been described often to psychiatric patients in general, although the alterations have been described often to be transient and that cases of clinically manifest thyroid disease are rare. be transient and that cases of clinically manifest thyroid disease are rare.
A screening test for thyroid function at admission should be part of any baseline work A screening test for thyroid function at admission should be part of any baseline work on newly admitted patients. on newly admitted patients.
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Stomatognathic Diseases
A number of studies highlight the poor dental status of A number of studies highlight the poor dental status of people with schizophrenia. people with schizophrenia.
Poor dental status can be a source of infections and Poor dental status can be a source of infections and endocarditis. endocarditis.
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Respiratory Tract Diseases
62% smoke (meta-analysis Leon 2006)62% smoke (meta-analysis Leon 2006)
A population-based study by Filik et al A population-based study by Filik et al (2006) found higher rates of lung (2006) found higher rates of lung impairment in people with schizophrenia impairment in people with schizophrenia compared with a UK national sample compared with a UK national sample
Chafetz et al (2005) also reported Chafetz et al (2005) also reported that that people with schizophrenia have high people with schizophrenia have high rates of chronic respiratory problemsrates of chronic respiratory problems
Filik R et al. Acta Psychiatr Scand. 2006;113:298-305. Chafetz L et al. Community Ment Health J. 2005;41:169-84.
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Otorhinolaryngologic Diseases
Middle ear disease and vestibular disease may be etiological factors contributing to the development of schizophrenia. A number of experimental studies are available, although Levy and colleagues 1983 concluded that the role of vestibular disease in schizophrenia is overestimated.
Deafness:
Some evidence that hardness of hearing is overrepresented in people with late life schizophrenia, but this is mainly discussed as an etiological factor (old review by Cooper 1976).
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Nervous System Diseases Extrapyramidal side-effects, akathisia, tardive dyskinesia:Extrapyramidal side-effects, akathisia, tardive dyskinesia: wide range of prevalence 2%-90% (Casey 1993)wide range of prevalence 2%-90% (Casey 1993)
14 studies showing that even 14 studies showing that even antipsychotic naïveantipsychotic naïve people with schizophrenia show people with schizophrenia show fine motor symptomsfine motor symptoms
Multiple sclerosis:Multiple sclerosis:Geographical similarities of distribution (Templer et al. 1985)Geographical similarities of distribution (Templer et al. 1985)
Myasthenia gravis:Myasthenia gravis:Negative association in a couple of case reportsNegative association in a couple of case reports
Epilepsy:Epilepsy: Huge literature, but only in the other directionHuge literature, but only in the other direction
CNS infections:CNS infections: see above see above
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Nervous System Diseases Amyotrophic lateral sclerosis:Amyotrophic lateral sclerosis: two case report about schizophrenic symptoms in a two case report about schizophrenic symptoms in a patient with ALSpatient with ALS
Alzheimer’s disease:Alzheimer’s disease:
Equal or slightly less than in the general population (Murphy et al. 1998), more studies Equal or slightly less than in the general population (Murphy et al. 1998), more studies are neededare needed
Blindness:Blindness: very rare in schizophrenia (Riscalla 1980) very rare in schizophrenia (Riscalla 1980)
Creatinine phospokinase activity (CPK):Creatinine phospokinase activity (CPK): increased together with increased together with
morphological changes of muscles of schizophrenics (Meltzer 1976)morphological changes of muscles of schizophrenics (Meltzer 1976)
Sleep problems:Sleep problems: sleep is disturbed in people with schizophrenia (Benca et al. 1992) sleep is disturbed in people with schizophrenia (Benca et al. 1992)
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Nervous System Diseases Pain insensitivity:Pain insensitivity:
A number of case series and many experimental studies showed a decreased pain A number of case series and many experimental studies showed a decreased pain sensitivity in people with schizophrenia.sensitivity in people with schizophrenia.
Important, because this may explain the decreased rates of some medical illnesses Important, because this may explain the decreased rates of some medical illnesses (polyarthritis) due to underreporting, but also why people with schizophrenia develop (polyarthritis) due to underreporting, but also why people with schizophrenia develop these diseasesthese diseases
Hypotheses:Hypotheses:
Analgetic effects of antipsychotic drugs, basic deficit of schizophrenia for example as Analgetic effects of antipsychotic drugs, basic deficit of schizophrenia for example as the expression of a disturbed psycho-physiological development, inability of sensing the expression of a disturbed psycho-physiological development, inability of sensing and communicating painand communicating pain
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Urologic and Male Genital Diseases Female Genital Diseases and Pregnancy Complications
Urinary incontinence:Urinary incontinence: two reports on the association two reports on the association with clozapinewith clozapine
Sexual dysfunction:Sexual dysfunction: frequently in schizophrenia, but frequently in schizophrenia, but further studies seem to be warrantedfurther studies seem to be warranted
Prostate cancer:Prostate cancer: the only specific cancer that was the only specific cancer that was consistently decreased in the individual studies consistently decreased in the individual studies (explained by effects of medication and decreased (explained by effects of medication and decreased sexual activity)sexual activity)
25
Female Genital Diseases and Pregnancy Complications Galactorrhea:Galactorrhea: very little epidemiological studies, rates between 10% -57%. RCT’s very little epidemiological studies, rates between 10% -57%. RCT’s were not screened, they should underestimate the risk by their nature.were not screened, they should underestimate the risk by their nature.
Amenorrhea:Amenorrhea: typical antipsychotics 18,8% - 78%, literature on atypical typical antipsychotics 18,8% - 78%, literature on atypical antipsychotics is mainly based on RCT’santipsychotics is mainly based on RCT’s
Cancer of breast, ovary, cervix uteri and corpus uteri:Cancer of breast, ovary, cervix uteri and corpus uteri: prolactin may be a prolactin may be a promoter of breast cancer. The results of the population based cancer studies about promoter of breast cancer. The results of the population based cancer studies about all these forms of cancer are contradictory with some studies finding increased risk, all these forms of cancer are contradictory with some studies finding increased risk, some reduced risk and some equal risk in schizophrenia.some reduced risk and some equal risk in schizophrenia.
Nulliparity and sexual activity are known risk factors for female cancersNulliparity and sexual activity are known risk factors for female cancers
26
Female Genital Diseases and Pregnancy Complications Obstetrical complications:Obstetrical complications: large literature (32 studies included), the vast majority large literature (32 studies included), the vast majority of which show increase rates of obstetrical complications in women with of which show increase rates of obstetrical complications in women with schizophrenia.schizophrenia.
Hypotheses:Hypotheses: environmental factors (smoking, drugs), socioeconomic factors (low environmental factors (smoking, drugs), socioeconomic factors (low income), pharmacological factors (medication), disease related (cognitive function, income), pharmacological factors (medication), disease related (cognitive function, self neglect)self neglect)
Unclear:Unclear: parental risk, which risk factors are the most important ones, is the risk parental risk, which risk factors are the most important ones, is the risk also increased in other psychiatric disorders, what is the best form of care for also increased in other psychiatric disorders, what is the best form of care for pregnant women with schizophreniapregnant women with schizophrenia
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Cardiovascular Diseases Many risk factors in the population:Many risk factors in the population: smoking smoking (62%!),(62%!), obesity, diabetes, obesity, diabetes, dyslipidemia, antipsychotic medication (QTc prolongation), little exercisedyslipidemia, antipsychotic medication (QTc prolongation), little exercise
21 studies were included and showed that overall the people with schizophrenia 21 studies were included and showed that overall the people with schizophrenia have high rates of cardiovascular problems such as ECG changes, arhythmias, have high rates of cardiovascular problems such as ECG changes, arhythmias, cardiac infarction or sudden cardiac death.cardiac infarction or sudden cardiac death.
More evidence can be derived from mortality studiesMore evidence can be derived from mortality studies
Stigma may play an important roleStigma may play an important role
28
Increased death rates of mentally ill people
(Lawrence and Coghlan N S W Public Health Bull 2002; 13(7): 155–158)
0 50 100 150 200 250
Suicide
Accidental death
Chronic obstructive pulmonary disease
Peneumonia & influenza
Other circulatory system
Cerebrovascular disease
Other ischaemic heart disease
Acute myocardial infection
Diabetes mellius
Malignant neoplasms
Death rate per 100,000 person-years
Mentally ill
WA population
Death Rates in People with Mental Illness Compared to the Rest of the Population, Western Australia, 1980-1998
Death Rates in People with Mental Illness Compared to the Rest of the Population, Western Australia, 1980-1998
29
Reduced access to services of mentally ill
(Lawrence and Coghlan N S W Public Health Bull 2002; 13(7): 155–158)
0 0.5 1 1.5 2 2.5 3
Depressive disorder
Adjustment reaction
Personality disorder
Neurotic disorder
Other psychosis
Affective psychosis
Schizophrenia
Alcohol/drugs
Dementia
Rate ratio
ProceduresHospitalisationDeath
IHD Hospitalisation Revascularisation Procedure and Death rates, by Principal Psychiatric Diagnosis, Western Australia, 1980-1998
IHD Hospitalisation Revascularisation Procedure and Death rates, by Principal Psychiatric Diagnosis, Western Australia, 1980-1998
30
Cardiovascular Diseases Many risk factors in the population:Many risk factors in the population: smoking smoking (62%!)(62%!), obesity, diabetes, , obesity, diabetes, dyslipidemia, antipsychotic medication (QTc prolongation), little exercisedyslipidemia, antipsychotic medication (QTc prolongation), little exercise
28 epidemiological studies were included and showed that overall the people with 28 epidemiological studies were included and showed that overall the people with schizophrenia have high rates of cardiovascular problems such as ECG changes, schizophrenia have high rates of cardiovascular problems such as ECG changes, arhythmias, cardiac infarction or sudden cardiac death.arhythmias, cardiac infarction or sudden cardiac death.
More evidence can be derived from mortality studiesMore evidence can be derived from mortality studies
Stigma may play an important roleStigma may play an important role
31
Miscellaneous topics
Eye Diseases
Hemic and Lymphatic Diseases
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Immune System Diseases
Disorders of Environmental Origin
Animal Diseases
Pathological Conditions, Signs and Symptoms
32
Limitations
Despite the enormous amount of references (44202) Despite the enormous amount of references (44202) identified by our review may not be complete. Most of identified by our review may not be complete. Most of the studies came from Europe and the US. the studies came from Europe and the US.
Modern systematic review methods such as meta-Modern systematic review methods such as meta-analysis were not possible, often due to the analysis were not possible, often due to the methodological heterogeneity of the studies identifiedmethodological heterogeneity of the studies identified
33
Origin of 225 epidemiological studies on the association between schizophrenia and physical illness
Leucht et al. 2006
Africa, 1.0%Latin America,
0.4%
Australia, 3.0%
Europe, 38.0%
Asia, 13.0%
North America, 45.0%
34
Medical Comorbidity With Schizophrenia Is Very Common
TuberculosisTuberculosis
HIV++HIV++
Hepatitis B/CHepatitis B/C
Osteoporosis/decreased bone Osteoporosis/decreased bone mineral densitymineral density
Poor dental statusPoor dental status
Impaired lung functionImpaired lung function
Sexual dysfunctionSexual dysfunction
Extrapyramidal side effects of Extrapyramidal side effects of antipsychotic drugs; motor signs antipsychotic drugs; motor signs in antipsychotic-naive patientsin antipsychotic-naive patients
Obstetric complications++Obstetric complications++
Hyperprolactinemia-related side Hyperprolactinemia-related side effects of antipsychotics (eg, effects of antipsychotics (eg, irregular menses, galactorrhea)irregular menses, galactorrhea)
Cardiovascular problems++Cardiovascular problems++
Hyperpigmentation (side effect of Hyperpigmentation (side effect of chlorpromazine)chlorpromazine)
Obesity++,Obesity++, diabetes, diabetes, hyperlipidemia, metabolic hyperlipidemia, metabolic syndromesyndrome
Thyroid dysfunctionThyroid dysfunction
Physical Disease With Increased Frequency in Schizophrenia
(++) very good evidence for increased risk (eg, population-based studies).
35
Summary
MeSH disease category MeSH disease category Physical disease with increased frequency in schizophreniaPhysical disease with increased frequency in schizophrenia
Bacterial infections and mycoses Tuberculosis (+)
Virus diseases HIV (++), hepatitis B/C (+)
Neoplasms Cancer in general (-)1
Musculoskeletal diseases Osteoporosis/decreased bone mineral density (+)
Stomatognathic diseases Poor dental status (+)
Respiratory tract diseases Impaired lung function (+)
Nervous system diseasesExtrapyramidal side-effects of antipsychotic drugs (+), motor signs in antipsychotic naive patients (+), altered (reduced) pain sensitivity (+)
Urological and male genital diseases Sexual dysfunction (+), prostate cancer (-)
Female genital diseases and pregnancy complications
Obstetric complications (++), sexual dysfunction (+), hyperprolactinemia related side-effects of antipsychotics (irregular menses, galactorrhea etc.) (+)
Cardiovascular diseases Cardiovascular problems (++)
Skin and connective tissue diseases Hyperpigmentation (+)2, rheumatoid arthritis (-)
Nutritional and metabolic diseases Obesity (++), diabetes (+), hyperlipidemia (+), metabolic syndrome including hyperlipidemia (+), polydipsia (+)
Endocrine system diseases Thyroid dysfunction (+), hyperprolactinemia (+) (side-effect of a number of antipsychotics)
Summary of physical diseases which occur with increased frequency in schizophrenia according to our review
(++) very good evidence for increased risk (e.g. population based studies), (+) good evidence for increased risk, (-) at least good evidence for decreased risk. 1 the results on specific forms of cancer were mostly inconclusive due to contradictory results and limited power2 a side-effect of chlorpromazine, probably not a problem of most other antipsychoticsThe table does not list physical diseases that have only been shown to be related to the etiology of schizophrenia (e.g. influenza virus). There were no clearly increased rates of physical diseases in the categories “parasitic diseases”, “digestive system diseases”, “otorhinolaryngological diseases”, “eye diseases”, “hemic and lymphatic diseases”, “congenital, hereditary, and neonatal diseases and abnormalities”, “immune system diseases”, “disorders of environmental origin”, “animal diseases”, “pathological conditions, signs and symptoms” or these diseases were listed in another category.
36
Conclusions
Morbidity in terms of rates of a number of physical Morbidity in terms of rates of a number of physical illnesses is clearly increased in schizophrenia.illnesses is clearly increased in schizophrenia.
The amount and quality of epidemiolgical studies found The amount and quality of epidemiolgical studies found in some areas – especially some hot topics – could be in some areas – especially some hot topics – could be better (e.g. obesity where more work is underway)better (e.g. obesity where more work is underway)
Surprising medical particularities such as decreased risk Surprising medical particularities such as decreased risk of cancer existof cancer exist
Future studies should focus on life style and stigma Future studies should focus on life style and stigma issues and prevention programmes are necessaryissues and prevention programmes are necessary
38
Acknowledgement
We thank the following experts for reviewing single chapters of publications that will be based on this review: Profs. and Drs. de Leon, Friedlander, Lawrence, Hatta, Templer, McCreadie, Perkins, Mortensen, Rybakowski, Steiner, Mondelli, Oken, Newcomer, and Cournos
39
BibliographyAllison DB, Fontaine KR, Heo M, Mentore JL, Cappelleri JC, Chandler LP, Weiden PJ, Cheskin LJ. The distribution of body mass index among Allison DB, Fontaine KR, Heo M, Mentore JL, Cappelleri JC, Chandler LP, Weiden PJ, Cheskin LJ. The distribution of body mass index among
individuals with and without schizophrenia. J Clin Psychiatry. 1999 Apr;60(4):215-20.individuals with and without schizophrenia. J Clin Psychiatry. 1999 Apr;60(4):215-20.
Allison DB, Casey DE. Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry. 2001;62 Suppl 7:22-31.Allison DB, Casey DE. Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry. 2001;62 Suppl 7:22-31.
Benca RM, Obermeyer WH, Thisted RA, Gillin JC. Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry. 1992;49(8):651-68; Benca RM, Obermeyer WH, Thisted RA, Gillin JC. Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry. 1992;49(8):651-68; 669-70. 669-70.
Casey DE. Neuroleptic-induced acute extrapyramidal syndromes and tardive dyskinesia. Psychiatr Clin North Am. 1993 Sep;16(3):589-610.Casey DE. Neuroleptic-induced acute extrapyramidal syndromes and tardive dyskinesia. Psychiatr Clin North Am. 1993 Sep;16(3):589-610.
CDC, Behavioral Risk Factor Surveillance System (BRFSS) 1991 and 2001. Graphic Breakdown: Domestic Impact of Obesity. In: A Handbook on CDC, Behavioral Risk Factor Surveillance System (BRFSS) 1991 and 2001. Graphic Breakdown: Domestic Impact of Obesity. In: A Handbook on Obesity in America. The Endocrine Society: May 2004. Reprinted January 2005: 38-42Obesity in America. The Endocrine Society: May 2004. Reprinted January 2005: 38-42
Chafetz L, White MC, Collins-Bride G, Nickens J. The poor general health of the severely mentally ill: impact of schizophrenic diagnosis. Chafetz L, White MC, Collins-Bride G, Nickens J. The poor general health of the severely mentally ill: impact of schizophrenic diagnosis. Community Ment Health J. 2005 Apr;41(2):169-84. Community Ment Health J. 2005 Apr;41(2):169-84.
Cooper AF. Deafness and psychiatric illness. Br J Psychiatry. 1976 Sep;129:216-26.Cooper AF. Deafness and psychiatric illness. Br J Psychiatry. 1976 Sep;129:216-26.
de Leon J, Verghese C, Tracy JI, Josiassen RC, Simpson GM. Polydipsia and water intoxication in psychiatric patients: a review of the de Leon J, Verghese C, Tracy JI, Josiassen RC, Simpson GM. Polydipsia and water intoxication in psychiatric patients: a review of the epidemiological literature. Biol Psychiatry. 1994 Mar 15;35(6):408-19.epidemiological literature. Biol Psychiatry. 1994 Mar 15;35(6):408-19.
Filik R, Sipos A, Kehoe PG, Burns T, Cooper SJ, Stevens H, Laugharne R, Young G, Perrington S, McKendrick J, Stephenson D, Harrison G. The Filik R, Sipos A, Kehoe PG, Burns T, Cooper SJ, Stevens H, Laugharne R, Young G, Perrington S, McKendrick J, Stephenson D, Harrison G. The cardiovascular and respiratory health of people with schizophrenia. Acta Psychiatr Scand. 2006 Apr;113(4):298-305. cardiovascular and respiratory health of people with schizophrenia. Acta Psychiatr Scand. 2006 Apr;113(4):298-305.
Lawrence D, Coghlan R. Health inequalities and the health needs of people with mental illness. N S W Public Health Bull. 2002 Jul;13(7):155-158. Lawrence D, Coghlan R. Health inequalities and the health needs of people with mental illness. N S W Public Health Bull. 2002 Jul;13(7):155-158.
Leucht S, Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry. Leucht S, Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry. 2006;67 Suppl 5:3-8. Review.2006;67 Suppl 5:3-8. Review.
Levy DL, Holzman PS, Proctor LR. Vestibular dysfunction and psychopathology. Schizophr Bull. 1983;9(3):383-438.Levy DL, Holzman PS, Proctor LR. Vestibular dysfunction and psychopathology. Schizophr Bull. 1983;9(3):383-438.
Meltzer HY. Serum creatine phosphokinase in schizophrenia. Am J Psychiatry. 1976 Feb;133(2):192-7. Meltzer HY. Serum creatine phosphokinase in schizophrenia. Am J Psychiatry. 1976 Feb;133(2):192-7.
Murphy GM Jr, Lim KO, Wieneke M, Ellis WG, Forno LS, Hoff AL, Nordahl T. No neuropathologic evidence for an increased frequency of Murphy GM Jr, Lim KO, Wieneke M, Ellis WG, Forno LS, Hoff AL, Nordahl T. No neuropathologic evidence for an increased frequency of Alzheimer's disease among elderly schizophrenics. Biol Psychiatry. 1998 Feb 1;43(3):205-9. Alzheimer's disease among elderly schizophrenics. Biol Psychiatry. 1998 Feb 1;43(3):205-9.
Riscalla LM.Blindness and schizophrenia. Med Hypotheses. 1980 Dec;6(12):1327-1328.Riscalla LM.Blindness and schizophrenia. Med Hypotheses. 1980 Dec;6(12):1327-1328.
Ryan MC, Collins P, Thakore JH. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry. Ryan MC, Collins P, Thakore JH. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry. 2003;160:284-289.2003;160:284-289.
Templer DI, Regier MW, Corgiat MD. Similar distribution of schizophrenia and multiple sclerosis. J Clin Psychiatry. 1985 Feb;46(2):73.Templer DI, Regier MW, Corgiat MD. Similar distribution of schizophrenia and multiple sclerosis. J Clin Psychiatry. 1985 Feb;46(2):73.