depression is a common mental disorder that is associated with functional impairment and high morbidity and mortality .
the world health organization ( who ) has reported that depression is the leading cause of disability in the world , and by 2020 , it will be the second greatest public health concern .
one of the important issues to note is that depression has been shown to have a higher prevalence in patients with somatic diseases than in healthy people .
a large , prospective , community - based study in canada found that 4% ( confidence interval [ ci ] : 3.34.7 ) of those with medical conditions versus 2.8% ( ci : 2.23.4 ) of those without developed depression over a 2-year period .
another study performed a meta - analysis of studies investigating the prevalence of depression in coronary heart disease ( chd ) in china , with the results showing that patients with chd had a high prevalence of depression : 51% in hospitals and from 34.6% to 45.8% in the community .
furthermore , it has been suggested that chronic somatic diseases might have a negative impact on the overall functioning , recognition rate , or treatment response of depressed patients , and that these patients are associated with a higher risk of recurrence or chronic course of depression .
furthermore , studies have suggested that depression has a high comorbidity with chronic somatic diseases .
for example , a meta - analysis of studies that tested the bi - directional relationship between depression and type 2 diabetes showed a high relative risk of 1.60 ( ci : 1.371.88 ) for the incidence of diabetes associated with depression .
another meta - analysis of the impact of depression on various cardiovascular diseases ( cvds ) showed that depression might be an independent risk factor for the onset of a wide range of cvds .
however , it is important to note that although a high comorbidity in depression and somatic diseases has been highlighted , few studies have comprehensively investigated and compared the socio - demographic characteristics , clinical symptoms , and antidepressant prescriptions of depressed patients with and without somatic comorbidity ( sc ) .
based on the above considerations , we conducted this study to investigate the prevalence of sc in depressed asian patients , and to determine the differences in socio - demographic characteristics , depressive symptoms , and prescription patterns of psychotropic drugs of depressed patients with and without sc .
the study was a part of the research on east asian psychotropic prescription patterns project , an international , cross - sectional , case record , and drug - centered study using a standardized data collection procedure in asian countries and territories .
the sample included 2320 outpatients or inpatients from 42 psychiatric centers in 8 asian countries : china ( including the mainland , hong kong sar , taiwan ) , india , indonesia , japan , the republic of korea , malaysia , singapore , and thailand .
a consensus meeting was held before the study to discuss methodological details , including uniformity of case selection , data collection , arrangement , and data entry procedures to assure comparability across sites and countries .
briefly , patients were included if they ( i ) had been prescribed antidepressants on the day of the survey ; ( ii ) could comprehend the aims of the study ; and ( iii ) agreed to participate in this study , and provided written or oral consent according to the requirements of the clinical research ethics committees at the respective study sites .
the clinical research ethics committees of the respective centers granted approval for the study protocol .
diagnoses were made according to the major , standard , international classification of disease , 10 revision ( icd-10 ) categories .
depression was defined as the presence of f32 or f33 in the icd-10 diagnostic system .
somatic diseases were self - reported diseases monitored by a healthcare professional and/or treated with medication .
we listed 17 common physical disorders : myocardial infarction , congestive heart failure , peripheral vascular disease , cerebrovascular disease , dementia , chronic pulmonary disease , rheumatic disease , peptic ulcer disease , mild liver disease , diabetes without chronic complications , diabetes with chronic complications , hemiplegia or paraplegia , renal disease , any malignancy , moderate or severe liver disease , metastatic solid tumor , and hiv / aids .
we classified somatic diseases into 9 categories , and the percentages of patients with each category are shown in figure 1 .
endoc : endocrine system ; diges : digestive system ; nerv : nervous system ; circu : circulatory system ; neopl : neoplastic disease ; urina : urinary system ; sk - mu : musculoskeletal system ; respi : respiratory system .
the 10 depressive symptoms in this study were selected based on the national institute for health and care excellence guidelines , the icd-10 and the diagnostic and statistical manual of mental disorders - iv .
these are the core symptoms of depression that represent the mood and the vegetative and cognitive profiles of a depressive illness .
fifty - six antidepressants in the anatomical therapeutic chemical classification index by the who collaborating center for drug statistics methodology ( oslo ) were listed .
based on which chemicals in the brain they affect , the antidepressants were classified into 7 classes including tricyclic antidepressants , tetracyclic , monoamine oxidase inhibitors , selective serotonin reuptake inhibitors ( ssris ) , serotonin norepinephrine reuptake inhibitors ( snris ) , noradrenergic and specific serotonergic antidepressant ( nassa ) , and other newer antidepressants .
all analyses were performed using the statistical package for social sciences ( spss ) , version 21.0 ( spss inc . ,
comparisons of socio - demographic and clinical characteristics between the comorbidity group and the noncomorbidity group were performed with independent samples t - test or pearson chi - square tests , as appropriate .
the study was a part of the research on east asian psychotropic prescription patterns project , an international , cross - sectional , case record , and drug - centered study using a standardized data collection procedure in asian countries and territories .
the sample included 2320 outpatients or inpatients from 42 psychiatric centers in 8 asian countries : china ( including the mainland , hong kong sar , taiwan ) , india , indonesia , japan , the republic of korea , malaysia , singapore , and thailand .
a consensus meeting was held before the study to discuss methodological details , including uniformity of case selection , data collection , arrangement , and data entry procedures to assure comparability across sites and countries .
briefly , patients were included if they ( i ) had been prescribed antidepressants on the day of the survey ; ( ii ) could comprehend the aims of the study ; and ( iii ) agreed to participate in this study , and provided written or oral consent according to the requirements of the clinical research ethics committees at the respective study sites .
the clinical research ethics committees of the respective centers granted approval for the study protocol .
diagnoses were made according to the major , standard , international classification of disease , 10 revision ( icd-10 ) categories .
depression was defined as the presence of f32 or f33 in the icd-10 diagnostic system .
somatic diseases were self - reported diseases monitored by a healthcare professional and/or treated with medication .
we listed 17 common physical disorders : myocardial infarction , congestive heart failure , peripheral vascular disease , cerebrovascular disease , dementia , chronic pulmonary disease , rheumatic disease , peptic ulcer disease , mild liver disease , diabetes without chronic complications , diabetes with chronic complications , hemiplegia or paraplegia , renal disease , any malignancy , moderate or severe liver disease , metastatic solid tumor , and hiv / aids .
we classified somatic diseases into 9 categories , and the percentages of patients with each category are shown in figure 1 .
endoc : endocrine system ; diges : digestive system ; nerv : nervous system ; circu : circulatory system ; neopl : neoplastic disease ; urina : urinary system ; sk - mu : musculoskeletal system ; respi : respiratory system .
the 10 depressive symptoms in this study were selected based on the national institute for health and care excellence guidelines , the icd-10 and the diagnostic and statistical manual of mental disorders - iv .
these are the core symptoms of depression that represent the mood and the vegetative and cognitive profiles of a depressive illness .
fifty - six antidepressants in the anatomical therapeutic chemical classification index by the who collaborating center for drug statistics methodology ( oslo ) were listed . based on which chemicals in the brain they affect , the antidepressants were classified into 7 classes including tricyclic antidepressants , tetracyclic , monoamine oxidase inhibitors , selective serotonin reuptake inhibitors ( ssris ) , serotonin norepinephrine reuptake inhibitors ( snris ) , noradrenergic and specific serotonergic antidepressant ( nassa ) , and other newer antidepressants .
all analyses were performed using the statistical package for social sciences ( spss ) , version 21.0 ( spss inc . ,
comparisons of socio - demographic and clinical characteristics between the comorbidity group and the noncomorbidity group were performed with independent samples t - test or pearson chi - square tests , as appropriate .
of all the patients , 1240 were diagnosed with depression ; among them , 375 ( 30.2% ) had sc .
the most common somatic disease was diabetes ( n = 89 , 23.7% ) , followed by cerebrovascular disease ( n = 40 , 10.7% ) and peptic ulcer ( n = 26 , 6.9% ) .
the percentages of patients with each system of somatic diseases are shown in figure 1 .
as shown in table 1 , almost all of the patients were from psychiatric departments ; the average age of patients with sc was older than that of patients without sc ( 55.3 vs. 45.2 years , p < 0.001 ) , and patients with sc had a higher frequency of seeing doctors at general hospital ( 74.7% vs. 47.2% , p < 0.001 ) .
no significant differences were found between the two groups in gender distribution or current setting .
demographic characteristics of depressed patients with or without sc sc : somatic comorbidity ; psych : psychiatric hospital / psychiatry ; gene : general hospital . the number of patients with each depressive symptom and the respective percentages is listed in table 2 .
the two groups had different rates of four symptoms , with a higher frequency of persistent sadness and two vegetative symptoms ( including disturbed sleep and poor appetite ) in the sc group , but a higher frequency of cognitive symptoms ( including poor concentration or indecisiveness ) in the noncomorbidity group .
sc : somatic comorbidity ; sleep : disturbed sleep ; n ( % ) : the number and percentage of patients with such symptom .
the three most commonly used antidepressants were sertraline ( n = 245 , 19.6% ) , escitalopram ( n = 232 , 18.6% ) , and mirtazapine ( n = 201 , 16.1% ) .
ssris were the most commonly prescribed type of antidepressant ( n = 841 , 67.4% ) , followed by snris ( n = 213 , 17.1% ) and nassa ( n = 201 , 16.1% ) .
the between - group differences in the number and rate of patients with each type of antidepressant and other types of medication like antipsychotics are listed in table 3 . as indicated , the sc group had a lower rate of patients prescribed ssris and anti - parkinsonian drugs and a higher rate of nassa and sedative hypnotics than the group without sc .
differences in prescription of psychotropic drugs between the two groups ( n ( % ) ) * p<0.05 . sc : somatic comorbidity ; fgas : first - generation antipsychotics ; sgas : second - generation antipsychotics ; apss : antiparkinsonian drugs ; tcas : tricyclic antidepressants ; ssris : selective serotonin reuptake inhibitors ; snris : serotonin - norepinephrine reuptake inhibitors ; nassa : noradrenergic and specific serotonergic antidepressant .
of all the patients , 1240 were diagnosed with depression ; among them , 375 ( 30.2% ) had sc .
the most common somatic disease was diabetes ( n = 89 , 23.7% ) , followed by cerebrovascular disease ( n = 40 , 10.7% ) and peptic ulcer ( n = 26 , 6.9% ) .
the percentages of patients with each system of somatic diseases are shown in figure 1 .
as shown in table 1 , almost all of the patients were from psychiatric departments ; the average age of patients with sc was older than that of patients without sc ( 55.3 vs. 45.2 years , p < 0.001 ) , and patients with sc had a higher frequency of seeing doctors at general hospital ( 74.7% vs. 47.2% , p < 0.001 ) .
no significant differences were found between the two groups in gender distribution or current setting .
demographic characteristics of depressed patients with or without sc sc : somatic comorbidity ; psych : psychiatric hospital / psychiatry ; gene : general hospital .
the number of patients with each depressive symptom and the respective percentages is listed in table 2 .
the two groups had different rates of four symptoms , with a higher frequency of persistent sadness and two vegetative symptoms ( including disturbed sleep and poor appetite ) in the sc group , but a higher frequency of cognitive symptoms ( including poor concentration or indecisiveness ) in the noncomorbidity group .
sc : somatic comorbidity ; sleep : disturbed sleep ; n ( % ) : the number and percentage of patients with such symptom .
the three most commonly used antidepressants were sertraline ( n = 245 , 19.6% ) , escitalopram ( n = 232 , 18.6% ) , and mirtazapine ( n = 201 , 16.1% ) .
ssris were the most commonly prescribed type of antidepressant ( n = 841 , 67.4% ) , followed by snris ( n = 213 , 17.1% ) and nassa ( n = 201 , 16.1% ) .
the between - group differences in the number and rate of patients with each type of antidepressant and other types of medication like antipsychotics are listed in table 3 . as indicated , the sc group had a lower rate of patients prescribed ssris and anti - parkinsonian drugs and a higher rate of nassa and sedative hypnotics than the group without sc .
differences in prescription of psychotropic drugs between the two groups ( n ( % ) ) * p<0.05 . sc : somatic comorbidity ; fgas : first - generation antipsychotics ; sgas : second - generation antipsychotics ; apss : antiparkinsonian drugs ; tcas : tricyclic antidepressants ; ssris : selective serotonin reuptake inhibitors ; snris : serotonin - norepinephrine reuptake inhibitors ; nassa : noradrenergic and specific serotonergic antidepressant .
to the best of our knowledge , this is the first large - scale , multicenter , international study to survey the differences in demographic characteristics , symptoms , and prescriptions of depressed patients with and without sc in asia .
the main findings are that a high percentage of the surveyed depressed patients had sc , the comorbid depressed patients were more likely to seek help at general hospitals , three depressive symptoms had higher rates in the comorbidity group , and the rates of the prescription of nassa were different between the two groups .
another study reported that in 1209 depressed patients in the netherlands , 43% had at least one sc .
the star*d study found that two - third of depressed patients had at least one concurrent general medical condition . in 1240 surveyed depressed patients in asia , we found that 30% had sc , which is relatively lower than the previous studies . in our study , we surveyed the patients who were treated with antidepressants , which is different from other studies including all the patients with depression .
considering the higher patients were not recognized by clinicians and low rate of treatment for the patients with depression , the high rate of sc in depression is an important matter of public health concern in asian countries and territories . in our study ,
another interesting finding was that 46.25% ( n = 1173 ) of patients prescribed with antidepressants were not diagnosed with depression .
further , we found a higher rate of seeking help at general hospitals rather than psychiatric hospitals among depressed patients with sc ( 74.7% vs. 47.2% ) , and a higher prevalence of depressive symptoms , including depressed mood , disturbed sleep , and poor appetite . in line with our finding , a study conducted in china reported that the rate of sc was higher in depressed patients who first chose general hospitals .
that phenomenon may not be hard to understand given that comorbidly depressed patients predominantly report their somatic symptoms before any others .
the strong illness stigma reported in patients with mental disorders may be another important reason , which would mean that depressive symptoms are less discussed in general clinics .
these potential problems pose great challenges to clinicians in general hospitals , as several studies conducted in chinese general hospitals have reported low rates of recognition and treatment of depression .
moreover , some studies have shown that comorbid somatic diseases could prolong the duration of depression and that higher rates of comorbidity were associated with treatment resistance among depressed patients .
these findings , together with ours , suggest that it is important to identify and intervene in depression as early as possible in patients who have complaints of somatic discomfort .
specific examinations for symptoms such as depressed mood , disturbed sleep , poor or increased appetite , the latter two symptoms were recognized as the third factor of depression , would be helpful for the recognition of depression . as shown in this study , newer antidepressants , especially ssris ,
were still the most prescribed antidepressants for depressed patients , followed by other novel antidepressants , which is in accordance with the findings of previous studies conducted in asia .
furthermore , we found significant differences in rates of prescribing nassa between the two groups ( 13.5% vs. 22.1% , p < 0.001 ) . the reasons for this difference may be as follows .
because sc is associated with a higher frequency of treatment resistance in depressed patients , according to world federation of societies of biological psychiatry guidelines , a combination of an ssri and mirtazapine is an evidence - based choice in depressed patients for whom monotherapy has failed . and
it has special advantages over ssris in the treatment of certain symptoms , such as disturbed sleep , poor appetite , and sexual dysfunction .
a meta - analysis showed that ssris , especially citalopram , were associated with a dose - dependent increase in qtc interval .
a us food and drug administration safety announcement advocated that citalopram should no longer be used at doses above 40 mg / d because in higher doses , the drug could unfavorably change the electrical activity of the heart without additional benefits in the treatment of depression . however , it should also be noted that studies addressing the risks of other novel antidepressants are limited , and evidence - based guidelines for depressed patients with sc are unavailable .
it will thus be necessary to conduct large - scale clinical trials to test the advantages and disadvantages of other novel antidepressants and establish relevant guidelines for the use of these agents in depression with sc .
the data were collected from eight different countries , and each center chose a certain day to collect data .
second , because the study was conducted at hospitals or universities in major cities , the data may not be generalizable to rural areas and smaller cities .
it is possible that second - generation antidepressants are used much less at smaller hospitals or in rural areas due to a lack of financial support .
third , because of nonrandomized sampling method , the findings of this study may not be generalizable to the entirety of asia .
another limitation is the variation of sample size at each participating center , which might have influenced the overall results . in conclusion ,
the findings of this study suggest a high rate of sc in depressed patients in asia , which may pose great challenges for clinicians recognizing depression , especially those at general hospitals . for a more efficient recognition of depression
, clinicians should routinely examine symptoms related to emotions , sleep , and appetite when patients have complaints of somatic discomfort .
depressed patients with sc are more likely to use other novel antidepressants ; thus , large - scale clinical trials of the efficacy and side - effects of these agents are urgently needed to contribute to a final development of guidelines for their use in depression with sc .
 background : depression is often comorbid with chronic somatic diseases . 
 few previous studies have investigated the prevalence of somatic diseases in depression or the prescription pattern of antidepressants in comorbidly depressed patients in asia . 
 this study aimed to investigate the prevalence of somatic comorbidity ( sc ) in depression and compared the prescriptions of antidepressants in depressed patients with and without sc.methods:a total of 2320 patients treated with antidepressants in 8 asian countries were examined , and a diagnosis was based on the international classification of disease , 10th revision . 
 we listed 17 common chronic somatic diseases . 
 patients socio - demographic and clinical characteristics and psychotropic drug prescriptions were recorded using a standardized protocol and data collection procedure.results:of the patients examined , 1240 were diagnosed with depression and 30% of them ( n = 375 ) had sc . 
 the most common comorbid condition was diabetes ( 23.7% ) . 
 the patients with sc were more likely to seek help at a general hospital ( 74.7% vs. 47.2% ) , and had a higher incidence of symptoms involving sadness , disturbed sleep , and poor appetite . 
 noradrenergic and specific serotonergic antidepressant was prescribed more for patients with sc than for those without sc ( 30.4% vs. 22.9%).conclusions : sc is common in depressed asian patients . 
 it is important to strengthen the recognition of depression , especially in general hospitals and when patients report some somatic discomfort . 
 it is also a matter of urgency to establish evidence - based guidelines for the use of new antidepressants in depressed patients with sc . 
I
M
Study sample
Criteria of depression and somatic diseases
Classification of antidepressants
Statistical analyses
R
Prevalence of somatic diseases in depression
Group differences in socio-demographic characteristics
Group differences in depressive symptoms
Group differences in psychotropic medication prescriptions
D