Reevaluating the Use of Docusate in the Management of Constipation

Introduction

Constipation is a common disorder that has a prevalence of approximately 20% in the general population and occurs even more frequently in the elderly.¹ Constipation is generally characterized by infrequent bowel movements (BMs) over the course of a week (generally fewer than 3 BMs weekly), but patients may have a wide range of symptoms, including hard stools, a feeling of incomplete evacuation, abdominal discomfort, bloating, and distention, as well as other symptoms (eg, excessive straining and a sense of anorectal blockage during defecation).² Constipation may be secondary to other disorders, lifestyle factors, or drug therapy, and these situations may be managed by addressing the underlying cause(s). Alternatively, an identifiable cause may not be known and in such instances, the condition is referred to as primary or idiopathic constipation.³ Regardless of the etiology, pharmacologic intervention may be necessary to manage the associated symptoms.² Pharmacological agents used in the management of constipation fall within a variety of laxative classes, such as bulk forming agents (eg, psyllium), osmotic agents (eg, polyethylene glycol), stimulants (eg, bisacodyl, senna), lubricants (eg, mineral oil), chloride channel activator (lubiprostone), guanylate cyclase activator (linaclotide), and serotonergic agents (eg, tegaserod).¹ An additional class of agents used to manage constipation includes emollient laxatives. Docusate, a commonly used member of this class, is believed to act as a stool softening agent by increasing the amount of water and lipids the stool absorbs in the gut, resulting in a softer, easier-to-pass stool.⁴

Docusate, formerly known as dioctyl sulfosuccinate (DSS), was approved for use in the United States in 1957 and is available in 2 different salt forms: docusate sodium (Colace and others) and docusate calcium (Surfak and others).⁴ Docusate is available over the counter in numerous oral dosage forms as well as a rectal enema. The usual recommended adult dose of oral docusate is 100-300 mg/day for the sodium salt and 240 mg/day for the calcium salt.

In its 2013 Position Statement on Constipation, the American Gastroenterological Association (AGA) recommends that constipation be initially managed with a gradual increase in fiber intake (through dietary means and/or via supplementation) and/or with inexpensive osmotic agents, such as milk of magnesia or polyethylene glycol. The AGA recommends that low-cost stimulant laxatives be added to the initial agents when needed, and that newer, more costly agents be reserved for patients who do not respond to less costly laxatives.² Docusate is not included in the aforementioned recommendations, however, its use is common, with greater than 3.5 million prescriptions for docusate dispensed in the US in 2017.⁵ Moreover, docusate is listed on the World Health Organization’s Model List of Essential Medicines, which lists “the safest and most effective medicines needed in a health system”.⁶ Despite its popularity, evidence to support its use is limited.

Clinical Data

The earliest identified data on the clinical use of docusate dates back to 1956. At that time, Cass and Frederikdescribed a study involving 74 hospitalized patients who were treated for chronic constipation.⁷ In this randomized, double-blind, placebo-controlled, crossover study, patients were randomized to receive docusate sodium 60 mg daily for 20 days or placebo for 10 days. The investigators reported differences in the outcomes of stool consistency (3.64 vs 4.0, respectively [with 1 = watery and 5 = extremely hard]) and frequency of BM (4.55/patient/week vs 3.5/patient/week, respectively) in the docusate group as compared with placebo group. It is unclear whether these differences were statistically significant.

A 1968 article by Hyland and Foran describes a study involving 34 geriatric hospitalized patients who were being treated for chronic constipation.⁸ In this placebo-controlled, crossover study, patients were randomized to receive docusate sodium 100 mg or placebo 3 times daily for 4 weeks. The investigators reported that docusate increased stool frequency by a mean of 1 BM per week compared with placebo; this difference was found to be statistically significant.

In another article, published in 1976, Goodman et al. described a study that examined the use of docusate for the prophylaxis of constipation in 34 elderly hospitalized patients.⁷ Patients were randomized to receive docusate sodium (100 mg twice daily) or placebo. Outcome measures included the frequency and quality of BMs; no significant between-group differences were found in the aforementioned outcome measures over the course of the study. The authors concluded that routine prophylaxis with docusate at a dose of 100 mg twice daily is not effective in altering the incidence of constipation in a hospital setting.

In a 1978 article, Fain et al. described a study that assessed the use of 2 docusate salts in 46 elderly patients with chronic constipation who were residing in a retirement center.⁹ Patients were randomized to 1 of 3 arms: docusate sodium 100 mg daily, docusate sodium 100 mg twice daily, or docusate calcium 240 mg daily. All patients underwent a 2-week placebo run-in period followed by 3 weeks of treatment. At the conclusion of the treatment period, a statistically significant increase in the frequency of BMs was noted in the docusate calcium arm compared with that observed at the conclusion of the placebo run-in period (2.83/week vs 1.75/week). In contrast, no such differences were noted with the 2 regimens of docusate sodium. 

A 1991 article by Castle et al. describes a randomized, double-blind, crossover study involving 15 elderly nursing home residents, all of whom were on a bowel regimen before the onset of the study.7,8 Subjects were randomized to receive docusate calcium 240 mg twice daily or placebo for 3 weeks followed by a 2-week washout period before crossing over to the other arm. Outcome measures included stool frequency, stool consistency, the need for additional laxatives, and patients’ subjective experience. The investigators reported no significant differences in any of these outcome measures.

In the largest study to date involving the use of docusate, McRorie et al. assessed the comparative efficacy of psyllium and docusate sodium in the management of chronic idiopathic constipation.10 In this multi-site, double-blind study, 170 adult patients were randomized to receive psyllium 5.1 g twice daily (along with docusate placebo) or docusate sodium 100 mg twice daily (along with psyllium placebo). The study began with a 2-week placebo phase (baseline) followed by a 2-week treatment phase. Outcome measures included BM frequency, stool weight, total stool output, dry stool weight, stool water weight, stool water content, and a combined score of the aforementioned outcome measures. The investigators reported that in treatment week 2, BM frequency was significantly greater with psyllium than with docusate (3.5/week vs 2.9/week, respectively). Increases in total stool output (359.9 g/week vs 271.9 g/week, respectively) and stool water weight (84.0 g/BM vs 71.4 g/BM, respectively) were also significantly greater with psyllium than with docusate. Likewise, when compared with baseline values, psyllium resulted in a significantly greater increase in stool water content vs. docusate (2.33% vs 0.01%, respectively). The combined score of objective measures of constipation was also significantly greater with psyllium than with docusate.

Other outcomes measures were not statistically different. Notably, the focus of this study was a comparison of psyllium with docusate, and as such, the investigators did not report whether docusate resulted in significant improvements in the study’s outcomes when compared with baseline measures.

In the most recent study, Tarumi et al. assessed the efficacy of docusate sodium in hospice patients.11 In this prospective, randomized, double-blind, placebo-controlled trial, 74 patients were randomized to receive 1 to 3 sennoside tablets (8.6 mg/tablet) plus docusate sodium 200 mg twice daily or 1 to 3 sennoside tablets (8.6 mg/tablet) plus placebo for 10 days. The primary outcome measures were stool frequency, volume, and consistency. The investigators reported no significant differences between the 2 groups in regards to the primary outcome measures. The authors concluded that docusate plus sennosides was not more efficacious than sennosides alone in managing constipation in hospice patients.

In addition to the clinical studies reported above, 2 systematic reviews were identified which examined the clinical efficacy of docusate in the management of constipation. In a review of literature spanning the period of 1940-1997, Hurdon et al. identified 4 eligible prospective controlled trials which evaluated the efficacy of oral docusate in adults with chronic illness and identifiable risk factors for constipation, as well as in those with preexisting constipation.⁷ Based on their review, the authors concluded that treatment of constipation with docusate in chronically ill and terminally ill patients is based on inadequate experimental evidence. Notably, the 4 trials included in the Hurdon review have been previously summarized in this article.

Similarly, in 2005, Ramkumar and Rao conducted a systematic review of the efficacy and safety of medical therapies for the management of chronic constipation.⁸ In this review, the authors searched for randomized studies published between 1966 and 2003 that included adult patients. The search yielded 4 studies that examined the efficacy of docusate, all of which have been summarized in the current review. Based on the evidence, Ramkumar and Rao concluded that “[t]he efficacy of docusate in the treatment of constipation is modest at best”.

Conclusion

Although the use of docusate remains common, evidence to support its use is based on a small number of clinical trials which often carried significant limitations. Pharmacists should be mindful of the lack of robust evidence to support the use of docusate for the management of constipation. Considering its OTC status, pharmacists can and must play an active role in guiding patients on the selection of laxatives which are supported by sound evidence. Likewise, such guidance should be provided to other health care practitioners caring for patients who require the use of laxatives.

At the time of writing, Dr Chattah was a student at The Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University.

Dr Grossman is a drug information specialist at the International Drug Information Center and adjunct assistant professor at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University.

Dr Nathan is the director at the International Drug Information Center and associate professor at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University.

References

1. Vazquez Roque M, Bouras EP. Epidemiology and management of chronic constipation in elderly patients. Clin Interv Aging. 2015;10:919-930. doi:10.2147/CIA.S54304.

2. Bharucha AE, Dorn SD, Lembo A, Pressman A. American Gastroenterological Association medical position statement on constipation. Gastroenterology. 2013;144(1):211-217. doi:10.1053/j.gastro.2012.10.029.

3. Fabel PH, Shealy KM. Diarrhea, Constipation, and Irritable Bowel Syndrome. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill. Accessed April 28, 2020.

4. Docusate. In: Clinical Pharmacology [database online]. Elsevier Inc. Accessed April 28, 2020.

5. Medical Expenditure Panel Survey summary tables – Prescribed drugs. Agency for Healthcare Research and Quality. U.S. Department of Health and Human Services. Accessed April 28, 2020.https://meps.ahrq.gov/mepstrends/hc_pmed/.

6. Model List of Essential Medicines. 21st List 2019. World Health Organization. Accessed April 28, 2020. https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf?ua=1.

7. Hurdon V, Viola R, Schroder C. How useful is docusate in patients at risk for constipation? A systematic review of the evidence in the chronically ill. J Pain Symptom Manage. 2000;19(2):130-136. doi:10.1016/s0885-3924(99)00157-8.

8. Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. Am J Gastroenterol. 2005;100(4):936-971. doi:10.1111/j.1572-0241.2005.40925.x.

9. American College of Gastroenterology Chronic Constipation Task Force. An evidence-based approach to the management of chronic constipation in North America. Am J Gastroenterol. 2005;100 Suppl 1:S1-4. DOI:10.1111/j.1572-0241.2005.50613_1.x.

10. McRorie JW, Daggy BP, Morel JG, Diersing PS, Miner PB, Robinson M. Psyllium is superior to docusate sodium for treatment of chronic constipation. Aliment Pharmacol Ther. 1998;12(5):491-497. doi:10.1046/j.1365-2036.1998.00336.x.

11. Tarumi Y, Wilson MP, Szafran O, Spooner GR. Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients. J Pain Symptom Manage. 2013;45(1):2-13. doi:10.1016/j.jpainsymman.