FormalPara Key Points

This retrospective observational study was performed to assess the dose changes of bisacodyl during long-term treatment in patients with constipation.

Results demonstrated that bisacodyl could be prescribed at a stable dose when used for >28 days in real-world clinical practice.

No signs indicative of bisacodyl habituation were observed.

1 Introduction

Constipation is a common gastrointestinal disorder, and chronic constipation has been reported to have a prevalence of 14% in the general population [1]. Its prevalence increases with age and is one of the most common presenting complaints to primary care or general practitioners (GP) and subspecialty physicians, such as gastroenterologists [2, 3]. Various pharmacological treatments for constipation exist; among them, laxatives are commonly taken as over-the-counter (OTC) medicines [4, 5].

Bisacodyl (4,4′-diacetoxy-diphenyl-[pyridyl-2]-methane) is a locally acting stimulant laxative that has been in use since the 1950s for the treatment of constipation [6,7,8,9]. It is a prokinetic drug with a hydrogogue effect that acts locally in the large intestine by enhancing the colonic motility, reducing transit time, and increasing stool water content [2]. Bisacodyl is available in oral and rectal formulations, with different onsets of action. An oral dose of 5–10 mg once daily is recommended for adults, and treatment should be initiated with the lower dose (5 mg) based on available clinical trial data [6]. The dose can be subsequently adjusted based on individual requirements [2].

Bisacodyl is widely used for short-term treatment in adult patients based on the robust clinical trial data available [6,7,8]. There is less clinical evidence available on its long-term usage in patients with constipation despite its usage as a first-line treatment in patients with chronic constipation [10]. Potential habituation with a continuous dose increment over a longer period could be one of the safety concerns associated with the long-term use of stimulant laxatives in patients with chronic constipation [11, 12]. Hence, this ongoing concern of healthcare professionals needs to be addressed.

Available data on the continuous use of stimulant laxatives do not indicate habituation [13, 14]. In contrast to more recently approved drugs and polyethylene glycol, available clinical evidence on the long-term use of bisacodyl is limited; hence, real-world data from different sources are helpful to complement the clinical data. Thus, we used information from electronic medical records (EMRs) from The Health Improvement Network (THIN) French database. THIN is a large European database with fully anonymized and non-extrapolated patient data for research on laxatives. This allows for capturing disease management data in real-world practice. In this study, we aimed to investigate whether patients with constipation who require long-term use of bisacodyl remain on a stable dose after continuous long-term utilization beyond 28 days.

2 Methods

2.1 Study Design

This was a retrospective, population-based, observational cohort study that used patients’ EMR data from THIN French database to analyze the long-term management of chronic constipation with bisacodyl in adult patients between January 1, 2011, and December 31, 2019. The database is European General Data Protection Regulation compliant and provides fully anonymized and non-extrapolated physician-level patient EMR data of more than 3.9 million patients per year. Though this database provides patient data at both general practitioner (GP) and specialist level, in this study, we considered only the records of GPs. This study was performed in accordance with the guidelines for the International Conference on Harmonisation, Good Clinical Practice, Good Pharmacoepidemiology Practice, and the Declaration of Helsinki. Since this is a retrospective, observational study based on existing data collected by THIN database, written consent was not obtained from the patients.

2.2 Study Time Periods

This retrospective study's survey period was from January 1, 2011, to December 31, 2019. The long-term treatment period was defined as the first treatment period during which patients were prescribed bisacodyl for at least 28 days. The first day of bisacodyl prescription during the long-term period was defined as the index date. The first 6 months before the index date were considered the baseline period. Patients were followed up for 12 months after the long-term period corresponding to the last prescription date plus the days bisacodyl was supplied for per the last prescription (Supplementary Fig. 1, see the electronic supplementary material [ESM]). The primary and secondary outcomes were identified during this period.

2.3 Patient Eligibility Criteria

The study included adult patients (≥ 18 years of age) diagnosed with constipation and who had exposure to bisacodyl treatment for at least 28 days. Patients were considered eligible if they had at least one event with an International Classification of Diseases 10th Revision (ICD-10) code related to constipation (K590, constipation; K599, functional intestinal disorder, unspecified; or R194, change in bowel habit). Patients prescribed with at least one additional bisacodyl dose during the follow-up period without any missing information on dosage and prescription duration during the index and follow-up periods were eligible to participate in the study. Patients were excluded if they had secondary constipation due to celiac disease or inflammatory bowel diseases; were diagnosed once with irritable bowel syndrome; had at least one drug abuse of laxatives during the baseline period; missed participating in the study follow-up continuously (without an active presence in the database) for 12 months; or lacked a continuous active presence in the database for 6 months during the baseline period.

2.4 Study Outcomes

Baseline characteristics were defined by patient demographics, medical history, and associated comorbidities commonly recorded in THIN database.

The total bisacodyl exposure of at least 28 days was calculated over one single or multiple prescriptions allowing for a maximum gap of 3 days between each prescription in case of multiple prescriptions. Multiple prescriptions were combined into one single continuous treatment using a common programming approach within the database. The gaps of at least 3 days between two single prescriptions were identified to calculate refills and determine the continuous treatment duration. If there was no treatment gap of at least 3 days between two prescriptions, they were considered one single prescription. The duration of this new single prescription represents the total duration of the contributing prescriptions. The duration of the initial long-term prescription was derived using the total number of days between the index date and the end date of the last long-term prescription.

The primary outcome of this study was the dose change status (stable or higher and lower or higher only or lower only) of bisacodyl during the follow-up period from the initial dose of the long-term period in the long-term cohort. The initial dose was defined as the last dose prescribed during the last 3 days of the long-term period. If multiple prescriptions were recorded in the last 3 days of the long-term period, the average dose of all the prescriptions was considered the initial dose. All the prescriptions observed during the follow-up period, including the 28-day prescriptions, and that appeared for renewal were considered relevant for assessing the dose change from the initial dose.

Patients were considered on a stable dose if the initial dose and the dose during the follow-up period were the same. Patients who had a higher and lower follow-up dose than the initial dose were categorized under higher and lower doses. Similarly, patients who had a higher or lower dose during the entire follow-up than the initial dose were categorized as higher dose only and lower dose only, respectively.

The secondary outcomes included baseline parameters (demographic characteristics [age at the index date, gender, and body mass index], medical history, and comedications potentially impacting the bowel movements), the Charlson Comorbidity Index (CCI) [15,16,17], and follow-up parameters (annual healthcare consumption). The medication possession ratio (MPR) associated with bisacodyl during the follow-up period was also derived as:

$$\frac{\text{Sum of non-overlapped exposed days during the follow-up period}}{\text{Duration of the follow-up}}\times 100$$

2.5 Statistical Analysis

Only descriptive statistics were used. For each categorical variable, the number and proportion of patients with missing data are reported. Patients with missing data on continuous measures were excluded from descriptive summaries. Continuous variables were summarized using the means with standard deviations and the medians with inter-quartile range, minimum and maximum. The primary outcome was described overall and by the initial dose.

A sensitivity analysis of the primary outcome was conducted, considering the co-prescription of other laxatives and bisacodyl during the long-term and follow-up period. In addition, a subgroup analysis was carried out for primary outcome with the following subgroups: MPR ≥ 25% versus < 25% and long-term prescription duration < 90 versus ≥ 90 days.

The secondary outcomes were analyzed by the dose change status and the initial dose.

3 Results

3.1 Patient Disposition

The study enrolled 5725 bisacodyl users from THIN French EMR database. A total of 3863 (67.5%) patients had long-term bisacodyl exposure, of which 15% of patients (n = 579) had at least one bisacodyl prescription during the 1-year follow-up period; 7.0% (n = 270) had continuous enrolment for 6 months during the baseline period, and 5.8% (n = 224) had continuous enrolment for 12 months during the follow-up period. Bisacodyl dose and exposure duration were available for 218 (5.6%) patients during both the index and follow-up periods (long-term cohort) (Fig. 1).

Fig. 1
figure 1

Patient disposition. aICD-10 codes related to constipation were K59.0, K59.9, or R19.4. bICD-10 codes related to secondary constipation or laxative abuse were K90.0, K51.x, K58.x, and F55.2. ICD international classification of diseases

Full size image

3.2 Baseline Demographics, Comorbidities, Medications, and Constipation Risk Factors

The baseline characteristics defined by demographics, medical history, and comedications of the patients in the entire long-term cohort are shown in Table 1. Among the long-term cohort, the mean (± standard deviation [SD]) age at the index date was 71.5 (± 13.9) years, and the majority were women (62.4%). Most (90.4%) of the patients in the long-term cohort had no previous history of bisacodyl use. A total of 79 (36.2%) patients had at least one comorbidity, and the most frequently reported comorbidity was diabetes mellitus without chronic complication (17%), followed by chronic pulmonary disease (10.1%). Over one-third (42.7%) of patients were diagnosed with at least one constipation risk factor based on the ICD-10 diagnosis codes. The most frequently reported constipation risk factor was psychological disease (23.9%), followed by endocrine/metabolic disease (22.9%) and neurologic disease (2.3%). More than one-third (42.2%) of patients in the long-term cohort did not receive any comedication during the baseline period. Other laxatives (39.4%) were the most frequent among those who received comedications.

Table 1 Baseline demographics, comorbidities, medications, and constipation risk factors of the long-term treatment cohort
Full size table

3.3 Bisacodyl Exposure

3.3.1 Exposure During the Long-Term Period

A total of 218 patients who qualified for the long-term cohort had their first bisacodyl prescription for at least 28 days. The median (interquartile range [IQR]) long-term bisacodyl prescription length was 30 (30–84) days, and 19.7% of patients received bisacodyl for at least 90 days. The majority of patients (76.1%; n = 166) received bisacodyl 5 mg as the initial dose, followed by 7.5 mg (17.0%; n = 37) and 10 mg (6.9%; n = 15). Approximately half (46.8%) of the patients in the long-term cohort did not receive any comedications during the long-term period. Among those who received comedications, the most frequently prescribed ones were any laxative other than bisacodyl (other laxatives; 36.2%), followed by antispasmodic along with other laxative (10.1%) and antispasmodics (6.9%).

3.3.2 Exposure During the Follow-Up Period

Results are shown as median (IQR). The median bisacodyl exposure duration per patient was 84 (30–159) days. The total number of bisacodyl prescriptions in the entire long-term cohort was 860 with a median of 3 (1–5) bisacodyl prescriptions per patient. The median number of bisacodyl prescriptions per patient among those who initiated bisacodyl at 5 mg, 7.5 mg, and 10 mg was 2 (1–4), 3 (2–8), and 3 (1–6), respectively. The median prescription duration was 60 (30–90) days. The most common doses were 5 mg (68.8%), followed by 7.5 mg (23.3%) and 10 mg (6.5%). The median MPR for bisacodyl was 23% (8–44%), and more than half (59.6%) of patients had an MPR of < 25% (rarely renewed), whereas one-third (33.0%) had an MPR of 25% to < 80% (occasionally renewed) during the follow-up period (Table 2).

Table 2 Prescription parameters of bisacodyl during the follow-up period
Full size table

3.4 Primary Outcome

3.4.1 Dose Change During the Follow-Up Period

During the follow-up period, almost all (94.0%) patients in the long-term cohort remained on the same dose compared with the initial dose over the first year, whereas 2.8% (n = 6) of patients had a decreased dose, and 3.2% (n = 7) had an increased dose during the follow-up year compared with the initial dose (Fig. 2). Among the patients on the increased dose, six patients had their dose increased within the approved daily dose range of 5–10 mg; the remaining one patient’s dose was increased to 15 mg and remained stable for the remaining prescription period of 80 days. The patient received four prescriptions of bisacodyl 15 mg during this time. Similarly, most patients remained on their initial prescribed bisacodyl dose of 5 mg (95.8%), 7.5 mg (89.2%), and 10 mg (86.7%). A total of seven (4.2%) patients among those who were initiated at 5 mg increased their dose; none decreased their dose. For patients initiated at 7.5 mg and 10 mg, none increased their dose during the follow-up period, and four (10.8%) and two (13.3%) patients decreased their dose.

Fig. 2
figure 2

Proportion of patients with dose change during the follow-up period in the long-term cohort

Full size image

3.4.2 Sensitivity Analysis of Primary Outcome Co-Prescribed With Other Laxatives

Of the total long-term cohort, 129 (59.2%) patients never received co-prescription with laxatives during the long-term period; however, 24 (18.6%) of these patients had other laxatives co-prescribed with bisacodyl during the follow-up period (Supplementary Fig 2, see ESM). Of the remaining 89 (40%) patients who had previously received co-prescription with laxatives during the long-term period, 87.6% (n = 78) continued on the other laxatives in combination with bisacodyl during the follow-up period (Supplementary Fig 3, see ESM).

The sensitivity analysis results of dose change status within the entire long-term cohort and by initial bisacodyl dose were similar to those observed for the primary analysis. Most patients remained on their same initial prescribed dose (5 mg: 93.4%; 7.5 mg: 89.2%; and 10 mg: 86.7%). A total of nine (5.4%) patients who were initiated at 5 mg increased their dose to 7.5 mg. Of these, two patients on higher doses were identified newly with the sensitivity analysis, whereas the remaining seven patients on higher doses remained the same from the main analysis. One patient had the additional laxative dose increased or decreased three times during a prescription period of 398 days. The other patient remained stable on the additional laxative dose for 420 days and increased the dose thereafter for 120 days during the follow-up period.

3.4.3 Dose Change During the Follow-Up Period—Subgroup Analysis by Medication Possession Ratio Level

During the follow-up period, 130 (59.6%) patients had an MPR < 25%, and 88 (40.4%) patients had an MPR ≥ 25%. However, despite their MPR, 93–95% of patients initiating long-term bisacodyl remained on the same dosage over the first year. A very small proportion of patients among those with MPR < 25% (3.8%) and MPR ≥ 25% (1.1%) had their bisacodyl dose decreased over the follow-up period. Similarly, 3.1% of patients with MPR < 25% and 3.4% with MPR ≥ 25% had their bisacodyl dose increased over the follow-up period (Supplementary Fig 4, see ESM).

3.4.4 Dose Change During the Follow-Up Period—Subgroup Analysis by Long-Term Treatment Duration (< 90 days or ≥ 90 days)

During the follow-up period, 175 (80.3%) patients had a long-term prescription for < 90 days, and 43 (19.7%) patients had a long-term prescription for ≥ 90 days. Irrespective of the long-term prescription period, 93–95% of patients remained on the same initial bisacodyl dosage over the first year of the follow-up period. In both subgroups, the majority of the patients remained on their initial prescribed dose (< 90 days: 5 mg: 95.6%; 7.5 mg: 89.3%; 10 mg: 81.8%; ≥ 90 days: 5 mg: 96.7%; 7.5 mg: 88.9%; and 10 mg: 100.0%). Only one (4.4%) patient and two (3.3%) patients who were initiated at 5 mg increased their bisacodyl dose in the < 90 days’ and ≥ 90 days cohorts, respectively, over the follow-up period.

3.4.5 Baseline Parameters of Patients with Higher Dose

Among patients whose dose increased during follow-up (n = 7), three patients had at least one comorbidity at the baseline (two patients had chronic pulmonary disease, and one had diabetes without chronic complication). Only three patients received prior medication for constipation at the baseline (antispasmodic + another laxative [n = 2], other laxative only [n = 1]).

3.5 Secondary Outcomes

Due to the small sample size by dose change status, differences observed in the different outcomes among groups were considered descriptive.

3.5.1 Demographic Parameters by Dose Change Status

Baseline demographic parameters were almost similar to the entire long-term cohort when categorized by dose change status. Overall, 205 patients were on a stable dose. Patients who were on a stable dose (mean [SD]) were slightly older (72.0 [13.1] years) than those who had their dose decreased (61.7 [26.6] years) or increased (65.9 [21.1] years). The female gender was more prevalent in the group with the increased dose (71.4%) than in the group with the stable (62.4%) or decreased doses (50.0%).

3.5.2 Medical History by Dose Change Status

Patients whose dose decreased or increased did not seem to have received any bisacodyl previously, whereas only 21 (10.2%) patients on stable doses had received a previous bisacodyl dose. Based on the CCI, the proportion of patients diagnosed with at least one chronic comorbidity was lower among patients on a stable dose (35.1%) than on decreased (66.7%) or increased doses (42.9%). The frequency of at least one constipation risk factor was higher in those with decreased doses (66.7%) than the other two groups (increased 28.6%; stable: 42.4%).

The proportion of patients with no comedications was lower in patients on decreased doses (16.7%) than in patients on stable (42.4%) or increased doses (57.1%). Among those who received a comedication, the most common therapy was ‘other laxative only’ (stable: 40%; decreased only: 50%; and increased only: 14.3%). Macrogol (32.1%) was the most prescribed laxative, followed by ispaghula (14.2%) and macrogol combinations (12.4%) among patients on a stable dose. Due to the small sample size by dose change status, differences observed in the different outcomes among groups were considered descriptive but not confirmatory.

3.5.3 Follow-Up Comedications Potentially Impacting Bowel Movement Frequency

The frequency of follow-up comedications was mostly similar among the entire long-term cohort. The most common comedication was another laxative only (stable: 42%; decreased only: 66.7%; and increased only: 28.6%), and many patients did not receive a comedication (decreased only: 16.7%; stable: 28.3%; and increased only: 28.6%) (Table 3).

Table 3 Follow-up comedications by dose change status
Full size table

3.5.4 Baseline Parameters by the Initial Dose

Patients who were initiated on bisacodyl 10 mg dose were slightly younger than those who were initiated on 5 mg and 7.5 mg doses (64.5 vs 72.5 vs 70.0 years). The proportion of female patients was lower among those who were initiated on bisacodyl 7.5 mg than those who were initiated at a lower or a higher dose (7.5 mg: 51.4%; 5 mg: 64.5%; and 10 mg: 66.7%).

3.5.5 Medical History According to the Initial Dose

During the follow-up period, the proportion of patients who had no previous history of bisacodyl was lower among those who were initiated on bisacodyl 7.5 mg (64.9%) than among those who were initiated at a lower (95.2%) or higher dose (100%). The mean (± SD) CCI score was lower in the 10 mg group (0.3 [0.6]) than in the 5 mg (0.6 [0.9]) or 7.5 mg (0.7 [1.0]) groups; diabetes without chronic complication was the most frequent comorbidity among these patients (5 mg: 27 (16.3%); 7.5 mg: 8 [21.6%]; and 10 mg: 2 [13.3]). The proportion of patients with at least one constipation risk factor was lower in the 7.5 mg group than in other treatment groups (7.5 mg: 27.0%; 5 mg: 43.3%; and 10 mg: 73.3%).

3.5.6 Comedications During the Follow-Up Period by the Initial Dose

Follow-up comedications were almost similar to those observed in the entire long-term cohort when patients were categorized by the initial dose. Approximately one-fourth of the population in the 5 mg (25.9%) and half in the 7.5 mg (43.2%) groups did not receive any comedication. In contrast, this proportion was low (13.3% [n = 2]) in those who were initiated at a higher dose (10 mg). A slightly higher proportion (53.3% [n = 8]) of patients in the 10 mg group received other laxatives only as follow-up comedication than in the 5 mg (42.2% [n = 70]) and 7.5 mg (37.8% [n = 14]) groups. The proportion of patients who received antispasmodics alone as comedication was 6% (n = 10) in the 5 mg group and 5.4% (n = 2) and 6.7% (n = 1) in the 7.5 mg and 10 mg groups, respectively. Similarly, the frequency of patients receiving antispasmodic and other laxative with bisacodyl 5 mg, 7.5 mg, and 10 mg was 25.3% (n = 42), 13.5% (n = 5), and 26.7% (n = 4), respectively. A total of 143 (65.6%) patients received at least one other laxative as comedication. Among total prescriptions of “at least one other laxative” as comedication (n = 672), macrogol (29.2% [n = 196]) was the most prescribed medicine. The frequency of prescription of “at least one other laxative” among the 5 mg, 7.5 mg, and 10 mg groups was 515, 103 and 54, respectively.

4 Discussion

Clinical studies in adults have shown that bisacodyl is effective and well tolerated in treating patients with chronic constipation when given orally for up to 4 weeks [6, 8]. Bisacodyl was indicated for the treatment of occasional idiopathic constipation in France [18]. Clinical studies, practice guidelines, and review articles assessing long-term safety and efficacy recommend bisacodyl for treatment, including for a prolonged duration beyond 4 weeks [10, 13, 19]. Though the clinical experience and available data suggest no concerns with using these stimulant laxatives over a longer period, some clinicians are concerned that the prescription of bisacodyl may lead to drug dependency or damage to the gut wall [11, 20]. However, the pharmacological mechanism does not support this concern as the active metabolite of bisacodyl cannot be absorbed and pass through the blood–brain barrier to cause dependency [21]. These misperceptions by physicians are mainly due to historical, anecdotal evidence and unwarranted fears [22]. Chronic constipation is a common condition that impairs the quality of life of men and women of all ages [23]. Hence, safe and clinically effective treatment over a prolonged period is necessary to control constipation symptoms for a longer duration. Furthermore, the existing epidemiological studies indicated that there was no risk with frequent use of stimulant laxatives [10, 22, 24,25,26].

Herein, we described the results of a retrospective observational study of long-term bisacodyl prescription in patients diagnosed and followed by GP for constipation. Our study provides unpublished data on the long-term exposure of bisacodyl in treating constipation using data from THIN French EMR database. The use of an EMR database containing rich and detailed longitudinal clinical records allowed assessment of disease burden and disease management by the French GPs from a real-world perspective. THIN French database has well-populated data on prescription duration and has been widely used for observational research, including utilization studies, assessment of treatment patterns, and prescription reasons. This study has significant limitations. (i) Bisacodyl is available as both a prescription drug and OTC. THIN French EMR database does not capture OTC data, and thus only included patients who received bisacodyl via prescription. These patients might have more severe, difficult to manage constipation compared with OTC users. (ii) EMR databases are limited to information provided by GPs and specialists who are “part of the network”; this prevents a complete real-world picture of any clinical question studied. In France, GPs are the main/central referent outside primary care. (iii) The database does not provide full information about the techniques used for disease diagnosis; it only provides the diagnosis results. (iv) Potential selection bias could also be a limitation due to the retrospective nature of the study; however, sensitivity analysis confirmed that no bias was induced by inclusion and exclusion criteria on the profile of our analysis population.

Through the database, we explored dose changes of bisacodyl after continuous long-term utilization for at least 28 days and the characteristics of patients with constipation. Approximately 95% of the total population was confirmed for constipation with the help of ICD-10 coding. The ICD-10 code gives a clear impression of the investigated population (Supplementary Table S1, see ESM). Out of the total bisacodyl users identified in THIN French EMR database, nearly three quarters had at least one long-term bisacodyl exposure for at least 28 days during the eligibility period. Among the 218 patients who were designated as the long-term cohort, the most common initial treatment dose of bisacodyl was 5 mg (76.1%), and this indicates that most prescriptions followed the advice to start with the lower 5 mg dose as given in the product leaflet and the summary of product characteristics [9, 18]. Results from the baseline parameters suggested that the overall population in the long-term cohort is consistent with the population with chronic constipation described previously [1]; the majority of patients were elderly and female (62.4%) with an average body mass index (BMI) of 28.6 kg/m2.

The analysis of dose changes over time showed that most (94.0%) patients remained on the same dose of bisacodyl that was prescribed initially, and only 3.2% (n = 7) of them had an increased dose during the follow-up year. Of the entire long-term cohort, only one patient who was initiated at 5 mg increased their dose to 15 mg, which was beyond the approved dose range; however, the dose remained stable at 15 mg for the remaining 80 days. Though this dose increment seemed to be a deviation as the accepted dose range for the current study is 5–10 mg, bisacodyl 15 mg is an approved dose to treat constipation in the United States and Canada [9, 27]. No specific risk profile was observed in those seven patients who had their dose increased.

Since concomitant use of other medications was not an exclusion criterion, “other laxative (mainly macrogol)” were reported to be the most common comedication prescribed majorly for constipation in these patients. Sensitivity analysis of dose changes considering the co-prescription of other laxatives with bisacodyl during the long-term and follow-up periods revealed that most patients who received bisacodyl with other laxatives during the long-term period continued to receive other laxatives during the follow-up period as well, and they had a stable dose of bisacodyl during the follow-up period [28].

The frequency of patients experiencing at least one comorbidity based on the CCI was high (36.2%), with half of the patients in the long-term cohort diagnosed with at least one constipation risk factor (42.7%). Diabetes without chronic complications was the most frequently diagnosed comorbidity, whereas psychological disease was the most frequent constipation risk factor (23.9%) in these patients. It is well known that constipation is a frequent long-term consequence of diabetes in adult patients [29, 30]. With this fact, it is inferred that the associated comorbidity of diabetes might have led to prolonged use and increased bisacodyl dose in these patients.

The subgroup analysis by MPR revealed that most (59.6%) patients had an MPR of < 25% during the follow-up period, representing multiple switches from treatment to non-treatment. However, regardless of MPR, 93–95% of patients initiating long-term bisacodyl remained on the same dosage over the first year. This result suggests that continuous treatment over prolonged periods, which is commonly investigated in long-term clinical trials, is rare in real-world practice.

Some clinicians have raised potential habituation or tolerance concerns for long-term treatment with stimulant laxatives [11, 31]. Habituation is characterized by a gradual increase in drug usage over time [32]. In this study, a small proportion of patients either increased or decreased their dose within the approved dose range (except for one whose dose increased to 15 mg). Of note, no repeated increases in the bisacodyl dose were observed despite a considerable proportion of patients with comedications and comorbidities. These associated comorbidities might have deteriorated and led to a dose increase in these patients. Using an existing real-world database reflecting primary care management, this type of real-world study offers an opportunity to look into long-term data and, therefore, complements the available data. Overall, the study results for France are consistent with those of a previous real-world study conducted in Germany, which showed that bisacodyl could be prescribed for long-term use with well-maintained efficacy [13].

5 Conclusion

Results from this retrospective cohort study indicate that bisacodyl can be prescribed at a stable dose when used for > 28 days. The majority of patients remained on the initial dose; only a small proportion of patients increased or decreased their dose, suggesting a stable use of bisacodyl in real-world clinical practice. In line with previous studies, no signs indicative of habituation were observed. Further investigations may be warranted to better understand treatment patterns, including OTC usage and long-term adherence to bisacodyl treatment.