Pharmacologic Therapy for Functional Constipation

Source: de Geus A, Gordon M, Sinopoulou V, et al. Efficacy and safety of pharmacological therapies for functional constipation in children: a systematic review and meta-analysis. Lancet Child and Adol Health. 2025;9(12):848-856; doi: 10.1016/S2352-4642(25)00219-6.Investigators from multiple institutions conducted a systematic review and meta-analysis to assess the effectiveness of multiple pharmacologic agents for treatment of functional constipation in children. They used a standardized process to identify randomized trials comparing a pharmacologic therapy to placebo, to another medication, no treatment, or a non-pharmacologic treatment, for functional constipation in patients <18 years. Only studies in which a definition of functional constipation was provided and had a follow-up period of at least 2 weeks were included. Data extracted from the identified studies included pharmacologic agents assessed, number of participants evaluated, and outcomes. The primary outcome of the meta-analysis was treatment success, as defined by the authors of the original study. Secondary outcomes included defecation frequency and withdrawals due to adverse events (AEs). These outcomes were assessed for each pharmacologic agent separately. Dichotomous outcomes were evaluated using risk ratios (RRs), and continuous outcomes with mean differences (MDs) or standardized mean differences (SMDs).A total of 59 studies, with 7,045 children, met criteria for inclusion. Treatment success of polyethylene glycol was compared with placebo in 2 studies with 193 children. More patients treated with polyethylene glycol had successful treatment than those in the placebo group (65% vs 36%; RR, 1.74; 95% confidence interval [CI], 1.25, 2.41). Polyethylene glycol was associated with a higher rate of success that lactulose (8 studies, 585 patients; success rate, 72% vs 51%; RR, 1.35; 95% CI, 1.11, 1.64). Defecation frequency was slightly higher in those treated with polyethylene glycol than lactulose (SMD, 0.34; 95% CI, 0.14, 0.53). Rates of withdrawals because of AEs were 7% for children in each treatment group. In 3 studies that included 211 children, the pooled withdrawals due to AEs was 6% for those in the polyethylene group and 17% for those treated with magnesium hydroxide (RR, 0.38; 95% CI, 0.16, 0.92). Treatment success of linaclotide was not significantly greater than that of placebo in 2 studies that included 349 patients (RR, 1.21; 95% CI, 0.69, 2.13), but defecation frequency was higher in patients treated with linaclotide than in placebo recipients (MD, 1.10; 95%, 0.40, 1.80). Prucalopride was compared to placebo in 1 trial of 215 children; there was no difference between groups in rate of treatment success (14% and 8%, respectively; RR, 1.68; 95% CI, 0.77, 3.68), or defecation frequency. Finally, the addition of adding enema therapy to treatment with polyethylene glycol did not significantly increase treatment success rates compared to polyethylene alone (1 study, 102 children; RR, 1.33; 95% CI, 0.83, 2.14).The authors conclude that the results suggest that polyethylene glycol was the most effective therapy assessed for treatment of functional constipation in children.Dr Yimlamai has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Constipation is a prevalent pediatric problem, accounting for 3% to 5% of pediatric primary care visits, with functional constipation accounting for more than 95% of these visits.1 A lack of alarm signs (ie, recent weight loss/gain, anemia, fatigue, etc) in the history and normal physical examination can confirm the diagnosis prior to therapy. Over the past several decades, there has been a rapid growth in the medications and strategies that providers can use to manage this condition. So understanding the most effective medications for these cases is important to reduce the clinical burden.The current researchers performed a meta-analysis of more than 50 studies including more than 7,000 children. They examined the effectiveness of several common and uncommon therapies including osmotic laxatives such as polyethylene glycol (PEG), lactulose, and magnesium oxide, as well as newer therapies such as linaclotide and prucalopride. PEG routinely outperformed other therapies, although PEG also was the most-often studied treatment for this condition. Newer therapies showed modest improvements over placebo and were limited in the number of studies and recruited patients. Enema therapy, when used in combination with oral therapy, did not show significant improvement in efficacy, suggesting it should not be routinely recommended. For treatment-naïve paients, oral PEG can be considered as first-line therapy. Titrating the frequency and amount of PEG are reasonable treatment variables in the outpatient setting prior to a sub-specialist referral. The authors suggest that PEG should be considered standard of care from which future work/treatment can be compared.In the setting of functional constipation, oral PEG should be a primary provider’s first-line choice for therapy. The efficacy of alternative therapies is less certain in the general pediatric population.Functional constipation, characterized by infrequent hard stools without underlying organic cause, affects the social and physical well being of children.2 Thus, in addition to providing dietary and lifestyle advice, clinicians need to address persistent symptoms—underscoring the import of the current study.