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Comorbidity between common mental disorders and chronic somatic diseases in primary care patients
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General Hospital Psychiatry 32 (2010) 240 – 245
Comorbidity between common mental disorders and chronic somatic diseases in primary care patients☆ Margalida Gili, Ph.D.a,b,⁎, Angels Comas, M.D.c , Margarita García-García, M.D.d , Saray Monzón, M.A.a,b , Serrano-Blanco Antoni, M.D., Ph.D.b,e , Miquel Roca, M.D., Ph.D.a,b a
Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), University of Balearic Islands, 07122 Palma de Mallorca, Spain b Red de Actividades Preventivas y Promoción de la Salud en Atención Primaria (RediAPP), 08007 Spain c Almirall Medical Department, Barcelona, 08022 Spain d Biométrica Institut, 08028 Barcelona, Spain e Research and Development Unit, San Joan de Deu, 08950 Barcelona, Spain Received 16 November 2009; accepted 25 January 2010
Abstract Objective: To estimate the prevalence of the most common mental disorders in primary care patients with chronic somatic diseases based on physicians' diagnoses and compared with healthy probands. Method: A systematic sample of 7940 adult primary care patients was recruited by 1925 general practitioners (GPs) in a large cross-sectional national epidemiological study. The Primary Care Evaluation of Mental Disorders (PRIME-MD) was used as standardized instrument for the assessment of mental disorders. Medical diagnoses were provided by patient's GP. Results: The prevalence rate of mental disorder was significantly higher in patients with chronic somatic diseases (56.8%) compared with physically healthy subjects (48.9%; OR: 1.37). Prevalence of depressive and anxiety disorders is higher among individuals with neurological, oncological or liver disease. The differences are significant in all comparisons, with the exception of anxiety disorders in patients with musculoskeletal disorders. There is an increase in prevalence rates of mental disorders according to the number of somatic diseases. Conclusions: The study provides evidence of the comorbidity of common mental disorders and somatic diseases. We need a predominant focus on affective and anxiety disorders in primary care patients with chronic somatic diseases. Symptoms overlap makes it necessary to discriminate these differences more in detail in future studies. © 2010 Elsevier Inc. All rights reserved. Keywords: Comorbidity; Mental disorders; Somatic diseases; Primary care; PRIME-MD
1. Introduction Chronic somatic diseases are the main cause of disability throughout the world [1]. Mental diseases likewise affect a large percentage of the population and constitute another important cause of morbidity, mortality and disability [2,3]. Different studies have reported a high prevalence of mental disorders in patients with chronic somatic illnesses. Meta☆ The project was possible due to an unrestricted educational grant from Almirall Spain. ⁎ Corresponding author. Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), University of Balearic Islands, Palma de Mallorca, Spain. Tel.: +34 971 173081; fax: +34 971 173190. E-mail address: [email protected] (M. Gili).
0163-8343/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2010.01.013
bolic, gastrointestinal and pulmonary diseases, as well as cardiovascular, muskuloeskeletal and neurological diseases show the highest prevalence rates of mental disorder [4–6], although no powerful association between any specific medical illness with a particular mental disorder has been found [7]. Such comorbidity in turn results in a poorer prognosis, increased resource utilization, higher costs, disability and poorer treatment compliance [8–10]. Most of these studies have analyzed the prevalences of mental disorders in populations with specific chronic diseases such as asthma, arteriosclerosis or cancer, and have been limited to the prevalences of affective or somatization disorders, or to elderly population groups [8,11–14]. The NIMH Epidemiological Catchment Area Study [15] was the first study to include a broad range of
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chronic medical disorders and mental illnesses, though the medical diagnoses were based on reports from the patients themselves not on the information supplied by the attending physicians. Furthermore, all the subjects were outpatients and were recruited from general population. Recently, the World Mental Health Surveys included a limited range of self-reported chronic physical conditions (arthritis, heart disease, respiratory disease, chronic back/neck pain, chronic headache and diabetes) [10]. The differences in mental disorders rates among medical patients suggest that epidemiological data are largely dependent on clinical setting, sample composition, psychopathology, chronicity, age, inconsistent diagnostic criteria, overlapping symptoms and other features [16,17]. Most of these comorbidity studies were conducted in specialized services or specific groups and so might not be generalized to primary care patients. According to several epidemiologic studies, between 20% and 53% of primary care patients have a mental disorder [18–22]. Patients with medical–psychiatric comorbidity compose the majority of the population seen in primary care (PC). The aim of the present study was to estimate the comorbidity of common psychiatric disorders (affective and anxiety disorders) and complete range of medical diseases in a large sample of primary care patients; additionally, to analyze the relationship between the amount of somatic comorbidity and the higher risk for common mental disorders; to estimate if the prevalence rates of affective and anxiety disorders differ between different types of chronic somatic diseases; and finally, to find significant association between any specific medical illness and a particular mental disorder. This is the first nationwide cross-sectional epidemiological study carried out in the primary care setting in Spain and the largest in a European country. 2. Method 2.1. Sample and procedure A Spanish national cross-sectional epidemiological study was designed. Two thousand general practitioners (GPs) — distributed proportionally by provinces and health centers in Spain's 17 regional communities — were randomly selected to participate in this study. Male/female, rural/urban and age proportions were as well guaranteed. One thousand nine hundred twenty-five GPs joined the study after having received an open invitation (96.2% was the response rate). The GPs were instructed in the use of the instruments, which were presented in an easy-to-use computerized format specifically designed for the study. Each GP was asked to recruit four patients randomized by days of the week and timetables. In case of refusal or exclusion, the next patient attending the primary care unit was enrolled until each GP obtained a total of four cases. Because a priori sample size of 8000 patients was calculated, an additional random sample (n=300) was selected to achieve the target. Sixty data sets
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were excluded from analyses due to incomplete or missing data. Finally, 7940 patients were included. All patients gave their written informed consent. The recruitment period was 12 weeks. The Clinical Teknon Ethical Committee (Barcelona) approved the study. 2.2. Instruments 2.2.1. Mental disorders The Primary Care Evaluation of Mental Disorders (PRIME-MD) is an easy and brief diagnostic assessment tool [23]. It consists of two principal components: a patient's questionnaire, completed by the patient and a 12-page Clinician Evaluation Guide, a structured interview completed by primary care physicians. The PRIME-MD questionnaire can be used as a general screening procedure in all patients or as a diagnostic procedure in patients in whom a mental illness is suspected. It assesses the five groups of mental disorders that are most frequent in primary care: mood, anxiety, somatoform, alcohol-related and eating disorders. It is based on the DSM-IV diagnostic criteria, modified for use in primary care. Seven of the possible diagnoses correspond directly to DSM-IV categories. The eighth diagnosis is multisomatoform disorder and is adjusted for primary care. Four subthreshold diagnoses are included since certain disorders that do not meet DSM-IV criteria for specific disorder are likely to be severe enough to cause impairment in primary care patients (minor depressive disorder, somatoform disorder not otherwise specified, binge eating disorder and anxiety disorder not otherwise specified). The sensitivity and specificity values of the Spanish version of the PRIME-MD questionnaire are 81.4% and 66.1%, respectively [24,25]. 2.2.2. Chronic medical conditions World Health Organization medical diagnoses were provided by the patient's GP according to medical records revised on the basis of radiology or laboratory test data. Diagnoses were later coded by one of the investigators (MGG) using the Medical Dictionary for Regulatory Activities (MedDRA) an international medical coding system used in clinical trials and research. 2.3. Data analysis All the data were processed using the SPSS 16 for Windows. Prevalence rates (%) and 95% confidence intervals (CIs) (level of significance b.05) were calculated for diagnosis and group categories. Differences were tested by logistic regression analysis with mental diagnosis or mental diagnostic group as dependent variable and medical diagnosis or medical diagnosis group as independent variables. Since female and older patients with lower socioeconomic status tend to have more common mental and physical health problems, sex, age, education and employment status were considered as confounder variables. Nonparametric tests were applied when the criteria for normality were not met.
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M. Gili et al. / General Hospital Psychiatry 32 (2010) 240–245 Table 2 Diagnosis of mental disorder and number of comorbid medical diseases
3. Results Patients with medical diseases showed an increased risk of having any mental disorder compared with physically healthy subjects. When multivariate logistic regression analyses were conducted with adjustments for differences in sex, age, education and employment status, the prevalence rate of mental disorder (Table 1) was significantly higher in patients with chronic somatic diseases (56.8%) compared with physically healthy subjects (48.9%; AOR: 1.46). Table 2 shows increased prevalence rates of mental disorders according to the increasing number of somatic disease. Patients with four or more chronic diseases show the highest rates of mental disorders. Adjusted ORs of having a mental disorder increases as number of medical diseases rises. The prevalence for any mental disorder is higher in any categories of somatic diseases comparing with physically healthy subjects (Table 3) and the rates of mental disorders differ between specific kinds of somatic diseases being highest among hepatic (75.7%; AOR: 2.54), neurological (75.5%; AOR: 2.58), oncological (68%; AOR: 1.79) and gastrointestinal diseases (67.2%; AOR: 1.98). Table 4 shows the results obtained for each group of diseases with the different comorbid medical disorders. The prevalence of depressive conditions was higher among the subjects presenting neurological (60.4%, P b 0.01), oncological (56.6%, P b 0.01) and liver disease (51.4%, P b 0.01) than among patients with other medical conditions. The same order was seen to apply on considering anxiety disorders. The differences were significant in all comparisons made between the different groups of medical diseases and depressive disorders. The same is true for anxiety disorders, except as regards the group of subjects with musculoskeletal problems. In the case of the somatoform disorders, the comparison was no longer significant in the group of oncological diseases. Lastly, Table 5 shows the prevalence rates of major depressive disorder, generalized anxiety disorder (GAD) and panic disorder (PD) among the specific somatic illnesses. Significant differences were established between major depressive disorder and all the groups of medical disorders, with the exception of cardiovascular diseases. Likewise, in the case of GAD, no significant differences were established with either musculoskeletal or metabolic conditions. Table 1 Comorbidity of medical disease in primary care patients with and without mental disorders
Medical disease No medical disease
a
Mental disorder % (n)
No mental disorder % (n)
Adjusted OR (95% CI)
56.8 (2677)
43.2 (2036)
1.46 (1.32–1.61)
48.9 (1577)
51 (1650)
a Multivariate logistic regression analysis adjusted by sex, age, education and employment status.
Mental No mental Adjusted ORa disorder % (n) disorder % (n) (95% CI) No medical disease One medical disease Two medical diseases Three medical diseases Four or more medical diseases
48.9 (1577) 50.3 (1137) 58.6 (795) 65.1 (401) 71.9 (344)
51 (1650) 49.7 (1124) 41.4 (563) 34.9 (215) 28.1 (134)
1.19 (1.07–1.33) 1.80 (1.56–2.01) 2.89 (2.36–3.53) 4.20 (3–5.87)
a Multivariate logistic regression analysis adjusted by sex, age, education and employment status.
4. Discussion The main conclusion drawn from our study is the high comorbidity between the most common mental conditions (depressive and anxiety disorders) and medical diseases in patients seen in the primary care setting. To date, the great majority of studies analyzing medical–psychiatric comorbidity are not population-based or have not been conducted in the primary care setting [17]. The investigation of comorbidity in population-based samples or in PC is essential in order to minimize the effect or referral bias in psychiatric units or psychiatric inpatients. Another important conclusion is the correlation found between mental disease and the number of concomitant medical disorders. Patients with two or more somatic disorders show an increased risk when compared with subjects that have only one somatic disease. A certain number of studies have shown high levels of comorbidity between chronic medical disorders and depressive disorders [26]. There is a scarcity of studies regarding anxiety disorders in chronic medical patients. The published studies of anxiety disorders focus on a particular medical condition such as diabetes, hypertension, asthma or cardiac disease [11,27,28]. One important question is if the Table 3 Different types of medical diseases in patients with and without mental disorder Mental No mental Adjusted ORa disorder % (n) disorder % (n) (95% CI) Any cardiovascular disease Any respiratory disease Any gastrointestinal disease Any metabolic disease Any musculoskeletal disease Any neurological disease Any hepatic disease Any oncological disease
55.5 (977)
44.5 (783)
1.1 (0.98–1.26)
57.9 (463) 67.2 (923)
42.1 (336) 32.8 (451)
1.19 (1.01–1.38) 1.82 (1.61–2.07)
58.2 (620) 57.8 (1316)
41.8 (445) 42.2 (960)
1.19 (1.04–1.36) 1.17 (1.05–1.31)
75.5 (406)
24.5 (132)
2.58 (2.10–3.17)
75.7 (137) 68 (83)
24.3 (44) 32 (39)
2.54 (1.79–3.62) 1.79 (1.21–2.67)
a Multivariate logistic regression analysis adjusted by sex, age, education and employment status.
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Table 4 Different PRIME-MD mental disorder categories and medical comorbidities
Any cardiovascular disease Any respiratory disease Any gastrointestinal disease Any metabolic disease Any musculoskeletal disease Any neurological disease Any hepatic disease Any oncological disease
Affective disorder % (n)
Anxiety disorder % (n)
Somatoform disorder % (n)
Alcohol use/abuse % (n)
Eating disorder % (n)
38 (668)⁎ 41.1 (328)⁎⁎ 47.7 (656)⁎⁎ 41.2 (439)⁎⁎ 41.8 (952)⁎⁎ 60.4 (325)⁎⁎ 51.4 (94)⁎⁎ 56.6 (69)⁎⁎
21.7 (328)⁎⁎ 29.4 (235)⁎⁎ 34.6 (475)⁎⁎ 28.1 (299)⁎⁎ 25.9 (590) 47 (253)⁎⁎ 36.5 (66)⁎ 38.5 (47)⁎
28.5 (501) 28.8 (230) 38.9 (535)⁎⁎ 33.5 (357)⁎⁎ 32.9 (748)⁎⁎ 43.1 (232) 42 (76)⁎⁎ 6.6 (8)
9.3 (163) 13 (104)⁎⁎ 12.9 (177)⁎⁎ 8.4 (89) 6.4 (146)⁎⁎ 7.2 (39) 42 (76)⁎⁎ 6.6 (8)
2.1 (37) 2.6 (21) 3.2 (44)⁎⁎ 2.8 (30) 2 (45) 2.6 (14) 1.1 (2) 0.8 (1)
Multivariate logistic regression analysis adjusted by sex, age, education and employment status. ⁎ P b 0.05. ⁎⁎ P b 0.001.
association between anxiety or affective disorders and somatic diseases is nonspecific to any of these disorders or is specific to a particular common mental disorder. In our study depressive conditions most often show comorbidity with neurological, oncological and hepatic diseases, and this association is exactly the same in the case of anxiety disorders. The differences are significant for all the most comorbid medical disorders, with the only exception of the association between anxiety disorders and musculoskeletal diseases. It is also interesting the finding that gastrointestinal, neurological and hepatic diseases show the strongest correlations with the three main specific categories of mental diagnoses analyzed (major depressive disorders, GAD and PD). Unlike previous studies [4,29], we did not find significant relationship between musculoskeletal diseases and anxiety disorders, neither GAD nor PD. According to the data of the National Comorbidity Survey (NCS) [29], posttraumatic stress disorder (PTSD) had the greatest number of significant associations with chronic physical disorders. PTSD was not assessed in our study because is not an available diagnosis in the PRIME-MD. Somatoform disorders are also highly prevalent in the sample. Nevertheless, some somatic diseases such as oncological conditions do not present significant correlations to these mental disorders. There are problems of validity and Table 5 Medical diseases comorbidity and specific diagnosis of depressive (major depressive disorder) and anxiety disorders (GAD and PD)
Any cardiovascular disease Any respiratory disease Any gastrointestinal disease Any metabolic disease Any musculoskeletal disease Any neurological disease Any hepatic disease Any oncological disease
MDD % (n)
GAD % (n)
PD % (n)
30.5 (356) 33.9 (271)⁎ 41.1 (565)⁎⁎ 34.4 (366)⁎⁎ 33.9 (771)⁎⁎ 53.2 (286)⁎⁎ 45.9 (83)⁎⁎ 50.8 (62)⁎⁎
9.5 (167)⁎⁎ 15.1 (121)⁎ 16.7 (229)⁎⁎ 12.7 (135) 11.7 (267) 29.4 (134)⁎⁎ 21 (38)⁎⁎ 22.1 (27)⁎⁎
7.8 (137)⁎ 12.8 (102)⁎ 14.5 (199)⁎⁎ 11.3 (120) 10 (227) 24.2 (130)⁎⁎ 17.7 (32)⁎⁎ 15.6 (19)⁎
Multivariate logistic regression analysis adjusted by sex, age, education and employment status. MDD=major depressive disorder. ⁎ P b 0.05. ⁎⁎ P b 0.001.
reliability with these diagnoses which clearly generate controversy in the psychiatric literature and lie at the center of debate regarding psychological factors affecting medical conditions. These patients tend to attribute their problems to somatic rather than to psychological factors. The overlap of symptoms with both somatic diseases and mental disorders is so important that any conclusions drawn in this category would prove polemical [30,31]. In our study there is an association between alcohol use/ abuse and respiratory, gastrointestinal, musculoskeletal and hepatic disease but not with cardiovascular, metabolic, neurological or oncological disease. In recent studies this comorbidity between alcohol use/abuse and somatic disease was low due to the fact of the high prevalence of alcohol consumption in young population who usually do not show chronic physical conditions [22]. What can be concluded from these results about the nature of the relationship between mental and somatic illnesses? Despite statistical significance, the high prevalence of mental disorder in all patients with medical conditions means a lack of specificity of associations. The understanding mechanisms involved in the development of increased psychiatric morbidity in medical patients is complex and includes biological and psychosocial factors [6,17,32]. Some evidences suggest that mental disorders may be both a cause and a consequence of some medical illness. A revision of 66 published papers found excess mortality from both natural and unnatural causes among psychiatric patients [33]. The biological linkages remain poorly understood [16]. Certain authors [34] have postulated depression as a metabolic disorder conditioned by immune-inflammatory and endocrine processes, neurocognitive alterations and comorbidity with medical disorders evidenced by studies such as our own. Neither our study nor the majority of those published in the literature to date have been designed to describe an eventual etiological nature of the relationship between mental disorders and chronic somatic diseases. What are the strengths of this study? (1) We used a large PC sample from all adults' age groups and health regions, representative of the chronically ill Spanish population. (2) We used a standardized diagnostic interview (PRIME-MD)
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that assesses the five groups of mental disorders most prevalent in PC and based in DSM-IV criteria modified for this clinical setting. (3) Unlike most studies analyzing medical illness, in our study the medical diagnoses were based on PC physicians clinical records and not on a selfreported checklist presented to the patient. (4) Finally, multiple chronic somatic diseases were included. The study is not focused on specific somatic disease as cancer or asthma. Very few comorbidity studies comprise a complete range of somatic conditions. Among the limitations, we should mention the problems deriving from the use of the diagnostic instruments. The study was performed by a large number of primary care physicians, which may also have affected the interrater reliability, even though it was carried out with an instrument with well-established psychometric properties in primary care patients as the PRIME-MD. Another limitation would be the fact that the PRIME-MD only includes two specific diagnoses of anxiety disorder (PD and GAD) but does not contemplate social phobia or post-traumatic stress disorder. The comorbidity with other mental disorders and the severity of each chronic somatic-specific disorder have not been taken into account. The results of this kind of study have implications for health care strategies. Primary care physicians need adequate information on the forms of presentation of medical comorbidities of the most common mental disorders in primary care. Further clarification is needed with regard to differential diagnosis between depressive, anxiety and somatoform disorders because the overlap contributes to errors in the diagnosis and delays in the management and treatment of these patients. Only in this way we will be able to investigate possible risk factors or etiopathogenic mechanisms such as shared vulnerability, life style, habits or treatments. Acknowledgments We thank all the Spanish GP physicians of the SCREEN GROUP who participated in data collection. References
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Comorbidity between common mental disorders and chronic somatic diseases in primary care patients☆ Margalida Gili, Ph.D.a,b,⁎, Angels Comas, M.D.c , Margarita García-García, M.D.d , Saray Monzón, M.A.a,b , Serrano-Blanco Antoni, M.D., Ph.D.b,e , Miquel Roca, M.D., Ph.D.a,b a
Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), University of Balearic Islands, 07122 Palma de Mallorca, Spain b Red de Actividades Preventivas y Promoción de la Salud en Atención Primaria (RediAPP), 08007 Spain c Almirall Medical Department, Barcelona, 08022 Spain d Biométrica Institut, 08028 Barcelona, Spain e Research and Development Unit, San Joan de Deu, 08950 Barcelona, Spain Received 16 November 2009; accepted 25 January 2010
Abstract Objective: To estimate the prevalence of the most common mental disorders in primary care patients with chronic somatic diseases based on physicians' diagnoses and compared with healthy probands. Method: A systematic sample of 7940 adult primary care patients was recruited by 1925 general practitioners (GPs) in a large cross-sectional national epidemiological study. The Primary Care Evaluation of Mental Disorders (PRIME-MD) was used as standardized instrument for the assessment of mental disorders. Medical diagnoses were provided by patient's GP. Results: The prevalence rate of mental disorder was significantly higher in patients with chronic somatic diseases (56.8%) compared with physically healthy subjects (48.9%; OR: 1.37). Prevalence of depressive and anxiety disorders is higher among individuals with neurological, oncological or liver disease. The differences are significant in all comparisons, with the exception of anxiety disorders in patients with musculoskeletal disorders. There is an increase in prevalence rates of mental disorders according to the number of somatic diseases. Conclusions: The study provides evidence of the comorbidity of common mental disorders and somatic diseases. We need a predominant focus on affective and anxiety disorders in primary care patients with chronic somatic diseases. Symptoms overlap makes it necessary to discriminate these differences more in detail in future studies. © 2010 Elsevier Inc. All rights reserved. Keywords: Comorbidity; Mental disorders; Somatic diseases; Primary care; PRIME-MD
1. Introduction Chronic somatic diseases are the main cause of disability throughout the world [1]. Mental diseases likewise affect a large percentage of the population and constitute another important cause of morbidity, mortality and disability [2,3]. Different studies have reported a high prevalence of mental disorders in patients with chronic somatic illnesses. Meta☆ The project was possible due to an unrestricted educational grant from Almirall Spain. ⁎ Corresponding author. Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), University of Balearic Islands, Palma de Mallorca, Spain. Tel.: +34 971 173081; fax: +34 971 173190. E-mail address: [email protected] (M. Gili).
0163-8343/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2010.01.013
bolic, gastrointestinal and pulmonary diseases, as well as cardiovascular, muskuloeskeletal and neurological diseases show the highest prevalence rates of mental disorder [4–6], although no powerful association between any specific medical illness with a particular mental disorder has been found [7]. Such comorbidity in turn results in a poorer prognosis, increased resource utilization, higher costs, disability and poorer treatment compliance [8–10]. Most of these studies have analyzed the prevalences of mental disorders in populations with specific chronic diseases such as asthma, arteriosclerosis or cancer, and have been limited to the prevalences of affective or somatization disorders, or to elderly population groups [8,11–14]. The NIMH Epidemiological Catchment Area Study [15] was the first study to include a broad range of
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chronic medical disorders and mental illnesses, though the medical diagnoses were based on reports from the patients themselves not on the information supplied by the attending physicians. Furthermore, all the subjects were outpatients and were recruited from general population. Recently, the World Mental Health Surveys included a limited range of self-reported chronic physical conditions (arthritis, heart disease, respiratory disease, chronic back/neck pain, chronic headache and diabetes) [10]. The differences in mental disorders rates among medical patients suggest that epidemiological data are largely dependent on clinical setting, sample composition, psychopathology, chronicity, age, inconsistent diagnostic criteria, overlapping symptoms and other features [16,17]. Most of these comorbidity studies were conducted in specialized services or specific groups and so might not be generalized to primary care patients. According to several epidemiologic studies, between 20% and 53% of primary care patients have a mental disorder [18–22]. Patients with medical–psychiatric comorbidity compose the majority of the population seen in primary care (PC). The aim of the present study was to estimate the comorbidity of common psychiatric disorders (affective and anxiety disorders) and complete range of medical diseases in a large sample of primary care patients; additionally, to analyze the relationship between the amount of somatic comorbidity and the higher risk for common mental disorders; to estimate if the prevalence rates of affective and anxiety disorders differ between different types of chronic somatic diseases; and finally, to find significant association between any specific medical illness and a particular mental disorder. This is the first nationwide cross-sectional epidemiological study carried out in the primary care setting in Spain and the largest in a European country. 2. Method 2.1. Sample and procedure A Spanish national cross-sectional epidemiological study was designed. Two thousand general practitioners (GPs) — distributed proportionally by provinces and health centers in Spain's 17 regional communities — were randomly selected to participate in this study. Male/female, rural/urban and age proportions were as well guaranteed. One thousand nine hundred twenty-five GPs joined the study after having received an open invitation (96.2% was the response rate). The GPs were instructed in the use of the instruments, which were presented in an easy-to-use computerized format specifically designed for the study. Each GP was asked to recruit four patients randomized by days of the week and timetables. In case of refusal or exclusion, the next patient attending the primary care unit was enrolled until each GP obtained a total of four cases. Because a priori sample size of 8000 patients was calculated, an additional random sample (n=300) was selected to achieve the target. Sixty data sets
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were excluded from analyses due to incomplete or missing data. Finally, 7940 patients were included. All patients gave their written informed consent. The recruitment period was 12 weeks. The Clinical Teknon Ethical Committee (Barcelona) approved the study. 2.2. Instruments 2.2.1. Mental disorders The Primary Care Evaluation of Mental Disorders (PRIME-MD) is an easy and brief diagnostic assessment tool [23]. It consists of two principal components: a patient's questionnaire, completed by the patient and a 12-page Clinician Evaluation Guide, a structured interview completed by primary care physicians. The PRIME-MD questionnaire can be used as a general screening procedure in all patients or as a diagnostic procedure in patients in whom a mental illness is suspected. It assesses the five groups of mental disorders that are most frequent in primary care: mood, anxiety, somatoform, alcohol-related and eating disorders. It is based on the DSM-IV diagnostic criteria, modified for use in primary care. Seven of the possible diagnoses correspond directly to DSM-IV categories. The eighth diagnosis is multisomatoform disorder and is adjusted for primary care. Four subthreshold diagnoses are included since certain disorders that do not meet DSM-IV criteria for specific disorder are likely to be severe enough to cause impairment in primary care patients (minor depressive disorder, somatoform disorder not otherwise specified, binge eating disorder and anxiety disorder not otherwise specified). The sensitivity and specificity values of the Spanish version of the PRIME-MD questionnaire are 81.4% and 66.1%, respectively [24,25]. 2.2.2. Chronic medical conditions World Health Organization medical diagnoses were provided by the patient's GP according to medical records revised on the basis of radiology or laboratory test data. Diagnoses were later coded by one of the investigators (MGG) using the Medical Dictionary for Regulatory Activities (MedDRA) an international medical coding system used in clinical trials and research. 2.3. Data analysis All the data were processed using the SPSS 16 for Windows. Prevalence rates (%) and 95% confidence intervals (CIs) (level of significance b.05) were calculated for diagnosis and group categories. Differences were tested by logistic regression analysis with mental diagnosis or mental diagnostic group as dependent variable and medical diagnosis or medical diagnosis group as independent variables. Since female and older patients with lower socioeconomic status tend to have more common mental and physical health problems, sex, age, education and employment status were considered as confounder variables. Nonparametric tests were applied when the criteria for normality were not met.
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M. Gili et al. / General Hospital Psychiatry 32 (2010) 240–245 Table 2 Diagnosis of mental disorder and number of comorbid medical diseases
3. Results Patients with medical diseases showed an increased risk of having any mental disorder compared with physically healthy subjects. When multivariate logistic regression analyses were conducted with adjustments for differences in sex, age, education and employment status, the prevalence rate of mental disorder (Table 1) was significantly higher in patients with chronic somatic diseases (56.8%) compared with physically healthy subjects (48.9%; AOR: 1.46). Table 2 shows increased prevalence rates of mental disorders according to the increasing number of somatic disease. Patients with four or more chronic diseases show the highest rates of mental disorders. Adjusted ORs of having a mental disorder increases as number of medical diseases rises. The prevalence for any mental disorder is higher in any categories of somatic diseases comparing with physically healthy subjects (Table 3) and the rates of mental disorders differ between specific kinds of somatic diseases being highest among hepatic (75.7%; AOR: 2.54), neurological (75.5%; AOR: 2.58), oncological (68%; AOR: 1.79) and gastrointestinal diseases (67.2%; AOR: 1.98). Table 4 shows the results obtained for each group of diseases with the different comorbid medical disorders. The prevalence of depressive conditions was higher among the subjects presenting neurological (60.4%, P b 0.01), oncological (56.6%, P b 0.01) and liver disease (51.4%, P b 0.01) than among patients with other medical conditions. The same order was seen to apply on considering anxiety disorders. The differences were significant in all comparisons made between the different groups of medical diseases and depressive disorders. The same is true for anxiety disorders, except as regards the group of subjects with musculoskeletal problems. In the case of the somatoform disorders, the comparison was no longer significant in the group of oncological diseases. Lastly, Table 5 shows the prevalence rates of major depressive disorder, generalized anxiety disorder (GAD) and panic disorder (PD) among the specific somatic illnesses. Significant differences were established between major depressive disorder and all the groups of medical disorders, with the exception of cardiovascular diseases. Likewise, in the case of GAD, no significant differences were established with either musculoskeletal or metabolic conditions. Table 1 Comorbidity of medical disease in primary care patients with and without mental disorders
Medical disease No medical disease
a
Mental disorder % (n)
No mental disorder % (n)
Adjusted OR (95% CI)
56.8 (2677)
43.2 (2036)
1.46 (1.32–1.61)
48.9 (1577)
51 (1650)
a Multivariate logistic regression analysis adjusted by sex, age, education and employment status.
Mental No mental Adjusted ORa disorder % (n) disorder % (n) (95% CI) No medical disease One medical disease Two medical diseases Three medical diseases Four or more medical diseases
48.9 (1577) 50.3 (1137) 58.6 (795) 65.1 (401) 71.9 (344)
51 (1650) 49.7 (1124) 41.4 (563) 34.9 (215) 28.1 (134)
1.19 (1.07–1.33) 1.80 (1.56–2.01) 2.89 (2.36–3.53) 4.20 (3–5.87)
a Multivariate logistic regression analysis adjusted by sex, age, education and employment status.
4. Discussion The main conclusion drawn from our study is the high comorbidity between the most common mental conditions (depressive and anxiety disorders) and medical diseases in patients seen in the primary care setting. To date, the great majority of studies analyzing medical–psychiatric comorbidity are not population-based or have not been conducted in the primary care setting [17]. The investigation of comorbidity in population-based samples or in PC is essential in order to minimize the effect or referral bias in psychiatric units or psychiatric inpatients. Another important conclusion is the correlation found between mental disease and the number of concomitant medical disorders. Patients with two or more somatic disorders show an increased risk when compared with subjects that have only one somatic disease. A certain number of studies have shown high levels of comorbidity between chronic medical disorders and depressive disorders [26]. There is a scarcity of studies regarding anxiety disorders in chronic medical patients. The published studies of anxiety disorders focus on a particular medical condition such as diabetes, hypertension, asthma or cardiac disease [11,27,28]. One important question is if the Table 3 Different types of medical diseases in patients with and without mental disorder Mental No mental Adjusted ORa disorder % (n) disorder % (n) (95% CI) Any cardiovascular disease Any respiratory disease Any gastrointestinal disease Any metabolic disease Any musculoskeletal disease Any neurological disease Any hepatic disease Any oncological disease
55.5 (977)
44.5 (783)
1.1 (0.98–1.26)
57.9 (463) 67.2 (923)
42.1 (336) 32.8 (451)
1.19 (1.01–1.38) 1.82 (1.61–2.07)
58.2 (620) 57.8 (1316)
41.8 (445) 42.2 (960)
1.19 (1.04–1.36) 1.17 (1.05–1.31)
75.5 (406)
24.5 (132)
2.58 (2.10–3.17)
75.7 (137) 68 (83)
24.3 (44) 32 (39)
2.54 (1.79–3.62) 1.79 (1.21–2.67)
a Multivariate logistic regression analysis adjusted by sex, age, education and employment status.
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Table 4 Different PRIME-MD mental disorder categories and medical comorbidities
Any cardiovascular disease Any respiratory disease Any gastrointestinal disease Any metabolic disease Any musculoskeletal disease Any neurological disease Any hepatic disease Any oncological disease
Affective disorder % (n)
Anxiety disorder % (n)
Somatoform disorder % (n)
Alcohol use/abuse % (n)
Eating disorder % (n)
38 (668)⁎ 41.1 (328)⁎⁎ 47.7 (656)⁎⁎ 41.2 (439)⁎⁎ 41.8 (952)⁎⁎ 60.4 (325)⁎⁎ 51.4 (94)⁎⁎ 56.6 (69)⁎⁎
21.7 (328)⁎⁎ 29.4 (235)⁎⁎ 34.6 (475)⁎⁎ 28.1 (299)⁎⁎ 25.9 (590) 47 (253)⁎⁎ 36.5 (66)⁎ 38.5 (47)⁎
28.5 (501) 28.8 (230) 38.9 (535)⁎⁎ 33.5 (357)⁎⁎ 32.9 (748)⁎⁎ 43.1 (232) 42 (76)⁎⁎ 6.6 (8)
9.3 (163) 13 (104)⁎⁎ 12.9 (177)⁎⁎ 8.4 (89) 6.4 (146)⁎⁎ 7.2 (39) 42 (76)⁎⁎ 6.6 (8)
2.1 (37) 2.6 (21) 3.2 (44)⁎⁎ 2.8 (30) 2 (45) 2.6 (14) 1.1 (2) 0.8 (1)
Multivariate logistic regression analysis adjusted by sex, age, education and employment status. ⁎ P b 0.05. ⁎⁎ P b 0.001.
association between anxiety or affective disorders and somatic diseases is nonspecific to any of these disorders or is specific to a particular common mental disorder. In our study depressive conditions most often show comorbidity with neurological, oncological and hepatic diseases, and this association is exactly the same in the case of anxiety disorders. The differences are significant for all the most comorbid medical disorders, with the only exception of the association between anxiety disorders and musculoskeletal diseases. It is also interesting the finding that gastrointestinal, neurological and hepatic diseases show the strongest correlations with the three main specific categories of mental diagnoses analyzed (major depressive disorders, GAD and PD). Unlike previous studies [4,29], we did not find significant relationship between musculoskeletal diseases and anxiety disorders, neither GAD nor PD. According to the data of the National Comorbidity Survey (NCS) [29], posttraumatic stress disorder (PTSD) had the greatest number of significant associations with chronic physical disorders. PTSD was not assessed in our study because is not an available diagnosis in the PRIME-MD. Somatoform disorders are also highly prevalent in the sample. Nevertheless, some somatic diseases such as oncological conditions do not present significant correlations to these mental disorders. There are problems of validity and Table 5 Medical diseases comorbidity and specific diagnosis of depressive (major depressive disorder) and anxiety disorders (GAD and PD)
Any cardiovascular disease Any respiratory disease Any gastrointestinal disease Any metabolic disease Any musculoskeletal disease Any neurological disease Any hepatic disease Any oncological disease
MDD % (n)
GAD % (n)
PD % (n)
30.5 (356) 33.9 (271)⁎ 41.1 (565)⁎⁎ 34.4 (366)⁎⁎ 33.9 (771)⁎⁎ 53.2 (286)⁎⁎ 45.9 (83)⁎⁎ 50.8 (62)⁎⁎
9.5 (167)⁎⁎ 15.1 (121)⁎ 16.7 (229)⁎⁎ 12.7 (135) 11.7 (267) 29.4 (134)⁎⁎ 21 (38)⁎⁎ 22.1 (27)⁎⁎
7.8 (137)⁎ 12.8 (102)⁎ 14.5 (199)⁎⁎ 11.3 (120) 10 (227) 24.2 (130)⁎⁎ 17.7 (32)⁎⁎ 15.6 (19)⁎
Multivariate logistic regression analysis adjusted by sex, age, education and employment status. MDD=major depressive disorder. ⁎ P b 0.05. ⁎⁎ P b 0.001.
reliability with these diagnoses which clearly generate controversy in the psychiatric literature and lie at the center of debate regarding psychological factors affecting medical conditions. These patients tend to attribute their problems to somatic rather than to psychological factors. The overlap of symptoms with both somatic diseases and mental disorders is so important that any conclusions drawn in this category would prove polemical [30,31]. In our study there is an association between alcohol use/ abuse and respiratory, gastrointestinal, musculoskeletal and hepatic disease but not with cardiovascular, metabolic, neurological or oncological disease. In recent studies this comorbidity between alcohol use/abuse and somatic disease was low due to the fact of the high prevalence of alcohol consumption in young population who usually do not show chronic physical conditions [22]. What can be concluded from these results about the nature of the relationship between mental and somatic illnesses? Despite statistical significance, the high prevalence of mental disorder in all patients with medical conditions means a lack of specificity of associations. The understanding mechanisms involved in the development of increased psychiatric morbidity in medical patients is complex and includes biological and psychosocial factors [6,17,32]. Some evidences suggest that mental disorders may be both a cause and a consequence of some medical illness. A revision of 66 published papers found excess mortality from both natural and unnatural causes among psychiatric patients [33]. The biological linkages remain poorly understood [16]. Certain authors [34] have postulated depression as a metabolic disorder conditioned by immune-inflammatory and endocrine processes, neurocognitive alterations and comorbidity with medical disorders evidenced by studies such as our own. Neither our study nor the majority of those published in the literature to date have been designed to describe an eventual etiological nature of the relationship between mental disorders and chronic somatic diseases. What are the strengths of this study? (1) We used a large PC sample from all adults' age groups and health regions, representative of the chronically ill Spanish population. (2) We used a standardized diagnostic interview (PRIME-MD)
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that assesses the five groups of mental disorders most prevalent in PC and based in DSM-IV criteria modified for this clinical setting. (3) Unlike most studies analyzing medical illness, in our study the medical diagnoses were based on PC physicians clinical records and not on a selfreported checklist presented to the patient. (4) Finally, multiple chronic somatic diseases were included. The study is not focused on specific somatic disease as cancer or asthma. Very few comorbidity studies comprise a complete range of somatic conditions. Among the limitations, we should mention the problems deriving from the use of the diagnostic instruments. The study was performed by a large number of primary care physicians, which may also have affected the interrater reliability, even though it was carried out with an instrument with well-established psychometric properties in primary care patients as the PRIME-MD. Another limitation would be the fact that the PRIME-MD only includes two specific diagnoses of anxiety disorder (PD and GAD) but does not contemplate social phobia or post-traumatic stress disorder. The comorbidity with other mental disorders and the severity of each chronic somatic-specific disorder have not been taken into account. The results of this kind of study have implications for health care strategies. Primary care physicians need adequate information on the forms of presentation of medical comorbidities of the most common mental disorders in primary care. Further clarification is needed with regard to differential diagnosis between depressive, anxiety and somatoform disorders because the overlap contributes to errors in the diagnosis and delays in the management and treatment of these patients. Only in this way we will be able to investigate possible risk factors or etiopathogenic mechanisms such as shared vulnerability, life style, habits or treatments. Acknowledgments We thank all the Spanish GP physicians of the SCREEN GROUP who participated in data collection. References
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