Abstract
Abstract
Objectives
To investigate the prevalence, associated factors, treatment status and burden of constipation in workers with depression or anxiety.
Study design
This was a retrospective observational study using a pre-existing database.
Setting
Claims data from October to November 2022 and data from the survey conducted in November 2022 were extracted from the database.
Participants
This study included self-reported workers who completed the survey, after excluding those with major mental disorders diagnosed as distinct from depression or anxiety and constipation due to organic diseases identified by International Classification of Diseases (ICD-10) codes.
Outcome measures
The subjects were divided into three groups: treated depression/anxiety, untreated depression/anxiety and no depression/anxiety. The prevalence of constipation, factors associated with constipation and medications prescribed for constipation were analysed. Work productivity and quality of life (QOL) were compared between three subgroups based on constipation status: treated constipation, untreated constipation and no constipation subgroup.
Results
Of the 18 585 respondents in the analysis population, 950 respondents (5.1%) were classified into the treated depression/anxiety group, 6035 respondents (32.5%) into the untreated depression/anxiety group and the remaining respondents into the no depression/anxiety group (11 600 (62.4%)). The prevalence of constipation was 22.5% in the treated group, 22.3% in the untreated group and 10.4% in the no depression/anxiety group, respectively. Depression and anxiety severity were independently associated with an increased risk of constipation. In all groups, the most commonly prescribed drug class was osmotic laxatives. Work productivity and QOL tended to indicate a greater burden in the untreated constipation subgroup than in the treated or no constipation subgroups.
Conclusions
The prevalence of constipation was twice as high if workers had depression/anxiety. Considering that the comorbidity of constipation with mental disorders may increase multiple burdens, appropriate medical interventions are required to treat both mental (depression/anxiety) and physical (constipation) conditions. This should be widely recognised by physicians and employers.
Keywords: GASTROENTEROLOGY, Functional bowel disorders, Patient Reported Outcome Measures, Anxiety disorders, Depression & mood disorders, Quality of Life
Strengths and limitations of this study.
To our knowledge, this is the first study to investigate the prevalence of constipation, work productivity and quality of life among workers with depression/anxiety.
We used a pre-existing database uniquely composed of claims and survey data.
Because the data set consisted of employees of large companies and their dependents, and the survey was conducted among health promotion application users, the generalisability of the results is limited.
This study did not address the causal relationships between depressive or anxiety symptoms, treatment and constipation.
The possibility of misclassification cannot be excluded because of the nature of secondary data use; however, a combination of survey and claims data may compensate for the drawbacks of each data source.
Introduction
Constipation is a common gastrointestinal disorder. Recent studies have reported that chronic constipation is associated with various diseases1 and can influence prognosis.2 Therefore, constipation requires proper prevention and treatment. Constipation is classified into two types: primary constipation (eg, irritable bowel syndrome with constipation (IBS-C) and functional gastrointestinal disorder) and secondary constipation (eg, drug-induced constipation (DIC), symptomatic constipation and constipation due to organic diseases).3
Lifestyle modifications and pharmacological treatments are the cornerstones of constipation treatment. Recently, drugs with novel modes of action have been approved for the treatment of functional constipation, IBS-C and opioid-induced constipation. The approval of these medicines has widened the choice of pharmacological treatment for chronic constipation.4
The prevalence of functional constipation, defined based on the Rome IV criteria, has been reported to be 11.7% globally and 16.6% in Japan.5 In contrast, epidemiological data on secondary constipation are limited and require further clarification. Known risk factors for secondary constipation include mental disorders, such as depression and anxiety.6 The prevalence of constipation is expected to increase in these patients because these primary conditions themselves may induce symptomatic constipation,7 8 and/or some medications for treatment can induce DIC.9
Chronic constipation compromises work productivity and quality of life (QOL).10 11 Depression and anxiety independently compromise work productivity and/or QOL.12,14 Therefore, patients with depression/anxiety and concomitant constipation are expected to experience a heavier burden of impaired work productivity and QOL. Particularly in Japan, where the number of patients with mental disorders is increasing15 and falling birth rates and a super-ageing population are causing labour shortages, the maintenance of work productivity and QOL among workers is essential. Effective measures to address this need require an understanding of the magnitude and causes of this burden. Nevertheless, to the best of our knowledge, few studies have focused on constipation concomitant with mental disorders and the associated burdens.
We believe that this is the first and indispensable step to clarify the overall real-world situation of constipation complicated by depression or anxiety to reduce the burden. Therefore, this study aimed to investigate the prevalence of and factors associated with the occurrence, treatment status and burden of concomitant constipation, as a whole, in workers with depression or anxiety.
Methods
Study design and data source
This retrospective observational study used a pre-existing database managed by DeSC Healthcare, Inc, Tokyo, Japan (DeSC). The data set provided by the DeSC comprised online survey data and linked administrative claims data of individuals insured by multiple society-managed employment-based health insurance associations contracted by the DeSC who agreed to the secondary use of their data. Society-managed employment-based health insurance associations are among the employment-based insurers in Japan and cover employees of large companies and their dependents who are less than 75 years old.
Survey data were derived from an online survey conducted in November 2022 by DeSC as a part of the DeSC-initiated survey to the insured individuals who voluntarily registered with Kencom, a health promotion support application developed and managed by DeSC for the ≥19-year-old registrants. The survey included questions on the respondents’ lifestyle information, symptoms of depression, anxiety, constipation, work productivity and QOL (the questionnaire instruments included in the survey are detailed in online supplemental table 1).
Claims data recorded for the month of the survey and the previous month, that is, from 1 October 2022 to 30 November 2022 (claims data period), were extracted. Claims data included individual-level demographic and medical information on inpatient and outpatient services provided by healthcare providers (hospitals, clinics and pharmacies).
DeSC database contained the claims data of 1 142 905 individuals insured by society-managed, employment-based health insurance associations, as of June 2023, when the claims data from April 2014 to November 2022 were incorporated. Of these, data on approximately 950 000 employees aged 19–74 years and their dependent family members were available for secondary use. Approximately 230 000 insured individuals were registered users of Kencom.
Study population
This study included self-reported workers who completed the survey. Of these, we excluded individuals with major mental disorders distinct from depression or anxiety and those with underlying organic diseases, except constipation due to organic disease, based on the International Classification of Diseases (ICD-10) codes listed in online supplemental table 2.
The study population was divided into three groups based on the presence or absence of depressive or anxiety symptoms and their treatment status.
1) Treated depression/anxiety group
This group comprised individuals who visited physicians and were diagnosed with one or more depression or anxiety disorders as defined with reference to previous studies16 17 based on ICD-10 codes: F32 (depressive episode), F33 (recurrent depressive disorder), F34 (persistent mood (affective) disorders), F38 (other mood (affective) disorders), F39 (unspecified mood (affective) disorder), F40–F48 (neurotic, stress-related and somatoform disorders), during the claims data period (online supplemental table 3). This group was defined irrespective of whether medication was prescribed, as the treatment for these conditions does not necessarily require medication and those whose conditions were not severe enough to require any kind of treatment were unlikely to be diagnosed.
2) Untreated depression/anxiety group
This group comprised individuals who did not visit physicians for treatment of depression/anxiety, and had mild or more severe depression and anxiety based on the results of screening tools used in an online survey: Patient Health Questionnaire-9 (PHQ-9)18 and/or Generalised Anxiety Disorder-7 (GAD-7) scores of ≥5.19
3) No depression/anxiety group
This group comprised individuals who did not satisfy the definitions of 1) and 2).
To describe the background characteristics of the study population and the potential factors associated with constipation, we assessed the participants’ demographic, lifestyle and clinical characteristics. Demographic data (age and gender) were extracted from claims data. Lifestyle information, including dietary habits, regular exercise, smoking and alcohol consumption, was assessed based on survey data. Comorbidities (online supplemental table 4) and drugs prescribed for mental disorders (psychotropic drugs) and DIC-causative drugs including psychotropic drugs (online supplemental table 5) were identified based on the ≥1 corresponding code during the claims data period. The severity of depression and anxiety were assessed based on survey responses to questions from the PHQ-9 and GAD-7, respectively.
Outcomes
The primary outcome was constipation prevalence. The secondary outcomes were the factors associated with constipation, the percentage of prescribed constipation medications by drug class, and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI)20 and EuroQol 5 dimensions 5-level (EQ-5D-5L) scores21 stratified by constipation status (treated, untreated or no constipation).
Constipation
Constipation was defined when any of the following three definitions were met:
Definition 1: Constipation diagnosed and treated with prescription drugs
Confirmed by the claims database (diagnosis and prescription), diagnostic codes for constipation (F453 (psychogenic constipation), K589 (IBS-C) and K590 (eg, DIC, opioid-induced, functional and chronic constipation; complete list in online supplemental table 6)) and at least one prescription record of constipation medications listed in online supplemental table 7 during the claims data period.
Definition 2: Constipation treated with over-the-counter (OTC) drugs
Based on the survey response as using OTC drugs to treat constipation.
Definition 3: Constipation that met the diagnostic criteria, but was not treated
Satisfying the survey criteria,6 that is, having at least two symptoms of the followings: ≥1 out of 4 evacuation events (1) requires hard straining, (2) produces hard lumps or lumpy form, (3) leaves a sensation of incomplete evacuation, (4) leaves a sensation of anorectal obstruction/blockage and (5) requires manual manoeuvres to facilitate; and (6) spontaneous evacuation less than three times per week.
Additionally, to assess the constipation status, we extracted the survey data on the Constipation Scoring System (CSS), which measures the severity of constipation, yielding a score ranging from 0 to 30 with a higher score indicating worse symptoms22 and the duration of constipation.
Medications for treatment of constipation
Prescribed medications for the treatment of constipation were assessed (online supplemental table 7).
Work productivity and QOL
Work productivity and QOL were assessed based on survey data from the WPAI and EQ-5D-5L, respectively.
The WPAI measures the degree of the impact of a respondent’s health problems on their work and daily activities in the last 7 days in terms of absenteeism, presenteeism, overall work impairment and activity impairment.20 Higher scores indicate greater impairment in work productivity and daily activities. Based on the WPAI responses, we estimated the indirect costs incurred by multiplying the total work hours missed and spent with reduced productivity by the average hourly wage.23 24
The EQ-5D-5L measures a respondent’s health state at the time of the survey.21 The converted summary index score for the Japanese population ranges from −0.025 to 1 (0 denoting death and 1 full health).25 Respondents also rated their overall health status on a Visual Analogue Scale ranging from 0 to 100 (worst to best health state that a respondent could imagine).
Statistical analysis
Participant characteristics were descriptively summarised by depression/anxiety group (treated depression/anxiety, untreated depression/anxiety and no depression/anxiety). Categorical data were summarised with n (%) and continuous variables with mean±SD.
Within the depression/anxiety groups, we summarised the percentage of participants who satisfied any definition of constipation, excluding duplicate counts. Additionally, the percentage was summarised by PHQ-9 and GAD-7 severity grade, mild (score: 5–9) and moderate or severe (score: ≥10) in the untreated depression/anxiety group.
We explored the factors associated with constipation using logistic regression analysis. Univariate analysis included constipation as the dependent variable and the potential factors as independent variables. Multivariate analysis was also conducted using variables that were considered clinically relevant to constipation based on previous studies,6 that is, gender, age, dietary habits, regular exercise, smoking and alcohol consumption; PHQ-9 and GAD-7; comorbidities of interest (endocrine-metabolic disease, neurological disorder and collagenosis); and prescription of DIC-causative drugs. ORs for constipation and 95% CIs were estimated.
To describe the status of depression, anxiety and constipation, the PHQ-9, GAD-7, CSS scores and duration of constipation were summarised for the following subgroups: (1) constipation treated with prescription drugs, regardless of the use of OTC drugs; (2) constipation treated with OTC drugs only; and (3) untreated constipation.
Constipation medications were described for the ‘constipation treated with prescription drugs’ subgroup. The percentage of each prescribed drug class is summarised for each group.
To analyse work productivity and QOL, each group was stratified into three subgroups: (1) treated constipation (prescription and/or OTC), (2) untreated constipation and (3) no constipation. WPAI with indirect costs and EQ-5D-5L scores were compared among the three subgroups using the Wilcoxon rank-sum test. All analyses were conducted using SAS V.9.4 Release V.7.0 (SAS Institute, Cary, North Carolina, USA). No Missing data were imputed. Statistical significance was set at a two-sided p value <0.05. The analyses were exploratory and were not adjusted for multiplicity. The reported p values should be regarded as exploratory and not confirmatory.
Patient and public involvement
None.
Results
In the database, 21 754 individuals provided survey response data, and 19 386 reported that they were currently working. The exclusion of 801 respondents who satisfied the exclusion criteria resulted in 18 585 participants analysed. Of these, 950 respondents (5.1%) were classified into the treated depression/anxiety group (depression: 289, anxiety: 440 and both: 221), and 6035 respondents (32.5%) were in the untreated depression/anxiety group (depression: 2440, anxiety: 470 and both: 3125); the rest did not have depression or anxiety and were classified into the no depression/anxiety group (11 600 (62.4%)) (figure 1).
Figure 1. Participant disposition.
Participant characteristics
Females accounted for 34.0% of the overall analysis population, and the mean age was 49.4±10.2 (±SD). Most of the participants scored ‘minimal’ in PHQ-9 and GAD-7, which is not defined as depression or anxiety (66.9% in PHQ-9 and 78.0% in GAD-7, respectively). For others, the PHQ-9 category was classified as mild in 22.5% of participants, moderate in 7.0%, moderate-to-severe in 2.3% and severe in 1.0%; the GAD-7 category was mild in 15.2% of participants, moderate in 4.5% and severe in 1.9%. All groups had similar gender distributions and mean ages (table 1).
Table 1. Participant characteristics.
| Characteristics | Overall (N=18 585) | Treated depression/anxiety (N=950) | Untreated depression/anxiety (N=6035) | No depression/anxiety (N=11 600) |
| n | n (%) | n (%) | n (%) | |
| Gender*: female | 6311 (34.0) | 339 (35.7) | 2548 (42.2) | 3424 (29.5) |
| Age* (mean±SD), years | 49.4±10.2 | 49.2±9.7 | 46.9±10.0 | 50.7±10.0 |
| Dietary habits† | ||||
| Having three meals every day | 14 572 (78.4) | 735 (77.4) | 4325 (71.7) | 9512 (82.0) |
| Skipping meals ≥3 days per week | 4004 (21.5) | 213 (22.4) | 1710 (28.3) | 2081 (17.9) |
| Regular exercise†: no | 11 082 (59.6) | 610 (64.2) | 4082 (67.6) | 6390 (55.1) |
| Smoking† | ||||
| Currently smoking | 2248 (12.1) | 135 (14.2) | 746 (12.4) | 1367 (11.8) |
| Used to but not currently smoking | 5221 (28.1) | 252 (26.5) | 1551 (25.7) | 3418 (29.5) |
| Never | 11 099 (59.7) | 561 (59.1) | 3738 (61.9) | 6800 (58.6) |
| Alcohol consumption† | ||||
| Every day | 4798 (25.8) | 220 (23.2) | 1407 (23.3) | 3171 (27.3) |
| Sometimes | 6568 (35.3) | 289 (30.4) | 2111 (35.0) | 4168 (35.9) |
| Rarely (or cannot drink) | 7199 (38.7) | 439 (46.2) | 2517 (41.7) | 4243 (36.6) |
| Endocrine-metabolic disease*: yes | 1436 (7.7) | 123 (12.9) | 421 (7.0) | 892 (7.7) |
| Neurological disorder*: yes | 34 (0.2) | 7 (0.7) | 11 (0.2) | 16 (0.1) |
| Collagenosis*: yes | 15 (0.1) | 2 (0.2) | 4 (0.1) | 9 (0.1) |
| Degenerative disease*: yes | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Psychiatric disorder*: yes | 950 (5.1) | 950 (100.0) | 0 (0.0) | 0 (0.0) |
| DIC-causative drugs*: yes | 996 (5.4) | 613 (64.5) | 166 (2.8) | 217 (1.9) |
| PHQ-9† (n) | 18 537 (99.7) | 945 (99.5) | 6035 (100.0) | 11 557 (99.6) |
| Minimal: 0–4 | 12 434 (66.9) | 407 (42.8) | 470 (7.8) | 11 557 (99.6) |
| Mild: 5–9 | 4180 (22.5) | 306 (32.2) | 3874 (64.2) | 0 (0.0) |
| Moderate: 10–14 | 1303 (7.0) | 125 (13.2) | 1178 (19.5) | 0 (0.0) |
| Moderate–severe: 15–19 | 427 (2.3) | 65 (6.8) | 362 (6.0) | 0 (0.0) |
| Severe: 20–27 | 193 (1.0) | 42 (4.4) | 151 (2.5) | 0 (0.0) |
| GAD-7† (n) | 18 507 (99.6) | 945 (99.5) | 6020 (99.8) | 11 542 (99.5) |
| Minimal: 0–4 | 14 495 (78.0) | 528 (55.6) | 2425 (40.2) | 11 542 (99.5) |
| Mild: 5–9 | 2833 (15.2) | 226 (23.8) | 2607 (43.2) | 0 (0.0) |
| Moderate: 10–14 | 830 (4.5) | 126 (13.3) | 704 (11.7) | 0 (0.0) |
| Severe: 15–21 | 349 (1.9) | 65 (6.8) | 284 (4.7) | 0 (0.0) |
| EQ-5D-5L† (n) | 18 585 (100.0) | 950 (100.0) | 6035 (100.0) | 11 600 (100.0) |
| Summary index score (mean±SD) | 0.908±0.112 | 0.843±0.139 | 0.845±0.123 | 0.945±0.082 |
| EQ-VAS (mean±SD) | 79.2±15.4 | 71.7±18.6 | 70.9±17.0 | 84.2±11.7 |
Based on claims data.
Based on survey data.
DIC, drug-induced constipation; EQ-5D-5L, EuroQol 5 dimensions 5-level; EQ-VAS, EuroQol-Visual Analogue Scales; GAD-7, Generalised Anxiety Disorder-7; PHQ-9, Patient Health Questionnaire-9
Prevalence of constipation
As shown in figure 2, 2773 (14.9%) participants in the overall population satisfied any definition of constipation. The percentage of constipation in the treated (22.5%) and untreated depression/anxiety groups (22.3%) were almost twice of that in the no depression/anxiety group (10.4%). Constipation was not treated at hospitals/clinics in 74.3% (159/214) subjects in the treated depression/anxiety group, 93.4% (1258/1347) in the untreated group and 89.9% (1090/1212) in the no depression/anxiety group. The prevalence of constipation in the ‘mild’ and ‘moderate or severe’ depression/anxiety in the untreated depression/anxiety group was 20.1% (831/4136) and 27.2% (516/1899), respectively (online supplemental table 8).
Figure 2. Prevalence of constipation. OTC, over-the-counter. The figure shows the prevalence of constipation and its breakdown by definition, excluding duplicate counts. Bold numbers indicate the percentage of constipation (Definitions 1, 2 and 3) overall and in each participant group.
Factors associated with constipation
Univariate logistic regression analysis (online supplemental table 9) showed higher ORs with statistical significance for having constipation in PHQ-9 (cut-off ≥5; 2.417 (2.227, 2.623)) or GAD-7 (cut-off ≥5; 2.365 (2.168, 2.580)) versus score <5 for each measure. Moreover, the OR gradually increased with each one-grade increase in PHQ-9 (mild: 2.123, moderate: 2.890, moderate–severe: 3.502 and severe: 3.920, vs minimal) and GAD-7 (mild: 2.218, moderate: 2.551, severe: 3.209, vs minimal). Other factors associated with a higher OR included female gender, skipping meals, lack of regular exercise, endocrine-metabolic diseases, neurological disorders, collagenosis and DIC-causing drugs. Among the DIC-causing drugs, the OR was the highest for chemotherapeutic drugs (11.411 (1.034, 125.886)), followed by tetracyclic antidepressants (TCAs) (8.561 (1.430, 51.259)) and attention deficit hyperactivity disorder (ADHD) medications (5.083 (1.959, 13.185)).
A multivariate analysis (table 2) demonstrated the highest OR for constipation in females (2.407 (2.199, 2.635)), followed by the PHQ-9 severity grade (1-severity grade increment) (1.395 (1.303, 1.492)), the DIC-causative drug prescription (1.203 (1.070, 1.352)), skipping meals (1.182 (1.069, 1.306)) and the GAD-7 severity grade (1-severity grade increment) (1.154 (1.062, 1.255)).
Table 2. Multivariate logistic regression analysis to explore factors associated with constipation in the overall analysis population.
| Variables | OR (95% CI) | P value |
| Gender*: female (ref: male) | 2.407 (2.199, 2.635) | <0.001 |
| Age* (continuous) | 1.007 (1.002, 1.011) | 0.003 |
| Dietary habits†: skipping meals ≥3 days per week (ref: having three meals every day) | 1.182 (1.069, 1.306) | 0.001 |
| Regular exercise†: no (ref: yes) | 1.105 (1.011, 1.208) | 0.028 |
| Smoking† | ||
| Currently smoking (ref: never) | 1.105 (0.962, 1.269) | 0.623 |
| Used to but not currently smoking (ref: never) | 1.142 (1.028, 1.267) | 0.132 |
| Alcohol consumption† | ||
| Sometimes (ref: rarely (or cannot drink)) | 0.942 (0.855, 1.037) | 0.435 |
| Every day (ref: rarely (or cannot drink)) | 0.825 (0.736, 0.925) | 0.002 |
| PHQ-9†: minimal, mild, moderate, moderate–severe, to severe | 1.395 (1.303, 1.492) | <0.001 |
| GAD-7†: minimal, mild, moderate, to severe | 1.154 (1.062, 1.255) | <0.001 |
| Endocrine-metabolic disease*: yes (ref: no) | 1.112 (0.948, 1.303) | 0.191 |
| Neurological disorder*: yes (ref: no) | 1.611 (0.705, 3.680) | 0.258 |
| Collagenosis*: yes (ref: no) | 0.886 (0.243, 3.226) | 0.854 |
| DIC-causative drugs*: yes (ref: no) | 1.203 (1.070, 1.352) | 0.002 |
Based on claims data.
Based on survey data.
DIC, drug-induced constipation; GAD-7, Generalised Anxiety Disorder-7; PHQ-9, Patient Health Questionnaire-9
Status of depression, anxiety and constipation
The status of depression, anxiety, constipation and constipation duration by constipation treatment subgroups is summarised in online supplemental table 10.
Medication class for treated constipation
The classes of prescribed constipation medications are summarised in online supplemental table 11. The most commonly prescribed class was osmotic laxatives (saline cathartics) in all three groups (treated depression/anxiety: 47.3%; untreated depression/anxiety: 49.4%; and no depression/anxiety: 50.8%), followed by Chinese herbal medicines in the treated depression/anxiety (21.8%) and no depression/anxiety groups (20.5%) and stimulant laxatives (anthraquinone) (23.6%) in the untreated depression/anxiety group; these laxatives were used by 7.3% of the treated depression/anxiety group.
Work productivity and QOL
The WPAI scores with indirect costs tended to be higher, and the EQ-5D-5L summary index score was lower in both the treated and untreated depression/anxiety groups than in the no depression/anxiety group (figure 3). By constipation subgroups of the treated depression/anxiety group, the scores tended to indicate a greater burden in the untreated constipation subgroup than the other two subgroups, with the highest indirect cost (mean±SD: 1 149 337.3±12 728 06.4 Japanese yen (JPY) (US$7769.5±8604.2 as of 22 November 2023), 1 385 312.6±1 277 124.8 JPY (US$9364.7±8633.4) and 995 193.1±1 2699 24.2 JPY (US$6727.5±8584.7) in the treated, untreated and no constipation subgroups, respectively). The trend was more salient in the treated depression/anxiety group (eg, mean±SD activity impairment score: 31.4±31.0%, 41.4±30.6% and 27.2±29.1% in treated, untreated and no constipation subgroups, respectively; the observed p values for untreated versus treated or no constipation were p<0.05). The scores on all measures indicated greater impairment in work productivity and QOL in the untreated constipation subgroup than in the no constipation subgroup of the treated depression/anxiety group (p<0.05).
Figure 3. Work productivity and activity impairment with indirect cost (a) and quality of life (b). 1Constipation subgroups were defined as follows: (1) treated constipation (prescription and/or OTC) (‘Treated’ in the figure), (2) untreated constipation (‘Untreated’) and (3) no constipation subgroups (‘None’). 2Calculated by multiplying the total work hours missed and spent with reduced productivity by the average hourly wage (male: 1631 yen, female: 1290 yen as of June 2021).24 The mean (SD) of each score and cost, and p values for comparisons between treated versus untreated constipation, untreated constipation versus no constipation and treated constipation versus no constipation (Wilcoxon rank-sum test) are displayed. *Indicates p<0.05. WPAI score: a higher score indicated greater impairment in work productivity and daily activities. EQ-5D-5L, EuroQol 5 dimensions 5-level; JPY, Japanese yen; WPAI, Work Productivity and Activity Impairment Questionnaire: General Health.
Discussion
This study demonstrated for the first time that the prevalence of constipation was twice as high in workers with depression/anxiety as in those without depression/anxiety. Depression and anxiety were independent factors associated with constipation. Untreated concomitant constipation affects work productivity and QOL, with the highest indirect costs. These results suggest that concomitant constipation should be managed in addition to underlying diseases in working individuals with depression/anxiety.
In our analysis population, 10.3% and 6.3% of participants scored ≥10 on PHQ-9 and GAD-7, respectively, indicating the requirement for medical intervention. This prevalence was slightly higher than in a previous report (depression: 5.7%, anxiety: 4.2%) based on a household interview survey conducted in Japan between 2013 and 2015.26 The higher proportion in the present population may be related to the recent increase in these mental conditions as a result of the COVID-19 pandemic.27 The prevalence of constipation (14.9%) in the overall population was comparable to the previously reported prevalence (16.6%), which was defined based on the Rome IV criteria.5 However, differences in constipation definitions may not allow for direct comparison. In this study, the history of diagnosis and treatment provided at hospitals/clinics was confirmed using claims data, including the ICD-10 codes. Using claims data, the current study reflects the treatment status in daily clinical practice more accurately than a study based solely on self-administered surveys. Considering these methods and results, the present study population approximately represents the real-world situation of Japanese workers.
Depression and anxiety have been indicated as risk factors for constipation according to Japanese guidelines6 and previous studies.7 28 However, a few studies to date have investigated the prevalence of constipation in workers. Based on the results, constipation seems to be more common in workers with depression or anxiety than in those without these underlying diseases. Even in those with mild depressive/anxiety symptoms that required watchful waiting (PHQ-9 and GAD-7 scores of 5–9) in the untreated depression/anxiety group, the prevalence of constipation was 20.1%, which was about twofold of that in the no depression/anxiety group. This suggests that constipation can occur from a very early stage of depression/anxiety and may have a psychological impact on patients. The percentage rose to 27.2% in those with moderate or severe symptoms (the corresponding score of ≥10); the trend was supported by the finding that the likelihood of having concomitant constipation gradually increased with the depression/anxiety severity grade. Nevertheless, constipation was overlooked in approximately 75% of patients in the treated depression/anxiety group, even though they visited doctors for depression and anxiety. Given that a previous study reported that approximately 80% of patients with schizophrenia did not declare constipation to their psychiatrist, it may be generally left untreated in patients with mental disorders.29 These results may reflect patients’ emotional barriers to talk about constipation with physicians.30 Therefore, it is important that physicians, especially psychiatrists, focus not only on treating psychiatric symptoms but also on the comprehensive health of patients, including physical comorbidities such as constipation.31
Risk factors associated with constipation, such as female gender, depression, anxiety, skipping meals and physical inactivity,6 indicated high ORs in the present study. These results underscore the importance of lifestyle modifications and the treatment of mental disorders in managing constipation. In addition, many medications can result in DIC, particularly anticholinergic agents and psychotropic drugs.6 As DIC may affect treatment adherence,32 the prescription of DIC-causing drugs such as psychotropic drugs requires careful monitoring for the possibility of inducing constipation. Univariate analysis suggested that the likelihood of constipation was particularly high for TCAs (8.561 (1.430, 51.259)) and ADHD medications (5.083 (1.959, 13.185)) among psychotropic drugs (online supplemental table 9). However, interpretation of these associations may require caution because only a small number of participants were prescribed these drugs and the prevalence of constipation was similar between the treated and untreated depression/anxiety groups.
Because constipation incurs a substantial burden and may lead to serious consequences if left untreated, proper treatment is vital. In terms of burden, our results suggest that constipation comorbid with depression/anxiety may further reduce work productivity and QOL, which are impaired by depression/anxiety alone.33 34 Compared with the untreated depression/anxiety group, more participants in the treated depression/anxiety group were prescribed drugs for constipation (1.5% vs 5.8%). Considering the smaller burden (less effect on work productivity, less indirect cost and higher QOL) in participants treated for constipation with prescription drugs than in their untreated counterparts, encouraging patients with depression/anxiety to visit physicians for underlying diseases may reduce this burden. Moreover, the severity of depression and anxiety tended to be lower in the constipation subgroup treated with prescription drugs than in the untreated or treated with OTC drugs only subgroups. These results highlight the importance of receiving treatment from physicians for the management of both underlying diseases and constipation. Therefore, to reduce the burden on workers, visiting a physician and receiving medical treatment could contribute to better outcomes than self-medication or being left untreated for constipation. From an employer’s perspective, it is advisable to encourage employees to visit physicians by providing information on these diseases and the need for treatment.
Anthraquinone laxatives have various side effects.35,37 In some patients with mental disorders, long-term use of stimulant laxatives may induce physical and psychological dependence, leading to habituation and dose increases in clinical practice. Therefore, anthraquinone laxatives are recommended only for short-term use.6 Few patients in the treated depression/anxiety group were prescribed these agents, which may reflect the concerns and recommendations described above; however, it is difficult to draw definitive conclusions based on the limited data. Continuous efforts are required to disseminate information on safe laxative use, particularly in patients with mental disorders who are more likely to be dependent. Novel medications for opioid-induced constipation, such as lubiprostone and naldemedine, are available. However, no drugs have been proven to be effective and safe for DIC caused by other drugs than opioid. Studies specifically targeting symptomatic constipation are also limited, with only a few studies conducted on patients with symptomatic constipation.38 39 Further research is required to identify effective treatment options for the kind of constipation.
Based on the WPAI and QOL scores, concomitant constipation imposed a greater burden on patients with depression/anxiety regardless of treatment status, highlighting the need for treatment. In the treated depression/anxiety group, the untreated constipation subgroup reported greater impairment in some work productivity scores than the treated or no constipation subgroups. These results suggest that the diagnosis and treatment of constipation by medical institutions may contribute to reducing this burden. Furthermore, QOL was the lowest in the same subgroup, with a mean EQ-5D-5L score of 0.798, which was lower than the scores reported for other diseases generally characterised by impaired QOL, such as diabetes mellitus (0.901)40 and chronic low back pain (0.83).41 Therefore, appropriate therapeutic interventions for mental disorders and constipation are required to improve the QOL of patients with concomitant constipation and depression/anxiety. Herein, the association between certain types of constipation (eg, IBS-C) and psychiatric disorders (eg, obsessive-compulsive disorder) was not investigated because it was outside the scope of this study. However, different types or aetiologies of constipation and psychiatric disorders may lead to variations in their relationships. Therefore, future research is required to explore the differences between the subtypes, which may contribute to more specific therapeutic interventions to improve QOL based on individual backgrounds.
This study had some limitations. First, the generalisability of the results may be limited. The data set consisted of employees of large companies and their dependents, over-representing working individuals with relatively high socioeconomic status and underestimating those who left work because of severe depression or anxiety. Moreover, the survey was conducted among Kencom users, who were voluntarily using this health promotion application, predisposing the study population to be more health-conscious. Second, this study did not address any causal relationships between depressive or anxiety symptoms, treatment and constipation. Third, the possibility of misclassification cannot be excluded because of the nature of secondary data. For example, one of the three definitions of constipation was based solely on self-reported OTC drug use from survey data and may be subject to recall bias. To mitigate this risk, we set other definitions based on claims data of disease diagnosis and drug prescriptions, which are recorded for reimbursement purposes and may not necessarily reflect the true diseases. However, a combination of survey and claims data may compensate for the drawbacks of each data source. Finally, the untreated depression/anxiety group was defined based on participants’ self-reports on the PHQ-9 and GAD-7, and not on the physician’s diagnosis.
Conclusion
The present study demonstrated twofold higher prevalence of constipation in workers experiencing depression/anxiety and showed that depression and anxiety were independently associated with constipation. Considering that the comorbidity of constipation with depression/anxiety can be burdensome for patients and society, especially if left untreated, physicians should consider appropriate medical interventions for mental as well as physical conditions. Additionally, employers must promote regular check-up for employees to identify these conditions and encourage them to seek treatment to avoid a decline in work productivity and QOL.
supplementary material
Acknowledgements
The statistical analyses and medical writing were supported by Clinical Study Support, Inc., and were funded by Viatris Pharmaceuticals Japan, Inc.
Footnotes
Funding: This work was funded by Viatris Pharmaceuticals Japan Inc. (grant number: N/A).
Prepub: Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2023-083668).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Data availability free text: The data may be obtained from a third party as they are not publicly available. The data set supporting the findings of this study is available from DeSC Healthcare, Inc., Tokyo, Japan., independent of Viatris Pharmaceuticals Japan Inc. Viatris Pharmaceuticals Japan, Inc. was not involved in validating or storing the data analysed in this study. Restrictions apply to the availability of the data, which were used under license for the present study, and therefore, are not publicly available; however, data are available from the authors upon reasonable request and with permission from DeSC Healthcare, Inc.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Ethics approval: This study used pre-existing data that were provided in an anonymised form that could not be identified. Therefore, informed consent was not required. This study was approved by the Kitamachi Clinic Ethics Committee (Tokyo, Japan) (approval number: LUU09271), a third-party ethics review committee unaffiliated with Viatris Pharmaceuticals Japan, Inc. The study was conducted according to legal and regulatory requirements as well as scientific purpose, value and rigor.
Contributor Information
Yusuke Karasawa, Email: yusuke.karasawa@viatris.com.
Kazutaka Nozawa, Email: Kazutaka.Nozawa@viatris.com.
Keisuke Nomoto, Email: Keisuke.Nomoto@viatris.com.
Shin Fukudo, Email: sfukudo@med.tohoku.ac.jp.
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