A Systematic Review on the Use of Oral Therapeutic Agents in the Management of Constipation in Adult Patients With Parkinsonʼs Disease

Abstract

Introduction: Constipation is common in patients with Parkinson's disease (PD) and has been postulated as an early non-motor symptom that precedes the diagnosis of PD. Although constipation significantly affects PD patients' quality of life, the efficacy of oral therapeutic agents that treat constipation in PD is unclear. We aim to conduct a systematic review of the literature to evaluate the effect of oral agents on constipation in adult PD patients. Methods: A comprehensive literature search in Ovid MEDLINE, Embase, Cochrane Central Register of CT, Cochrane Database of SR and CINAHL was performed up to 13 April 2015 using various root words of Parkinson and constipation alone and in combination. Two authors (AA, YT) independently reviewed all abstracts. Disagreements were resolved with the third author (LL). Exclusion criteria include: no abstract, non-English papers, non-human studies, not prospective clinical studies, non-adult patients, not Parkinson's disease, and not a study on oral therapeutic agent. Methodological quality was assessed using Cochrane's Risk of Bias. Results: The search identified 3069 studies. After removing duplications and applying the exclusion criteria, 9 studies (Figure 1, involving 237 patients, mean age = 68.1 years) were included in the analysis. In general, study designs were heterogeneous and assessment of constipation outcomes varied significantly between studies. There were 3 double-blind randomized controlled trials (RCT): 1 on Macrogol, 1 on lubiprostone and 1 on tegaserod. Although 2 small open label non-RCT (n=39) on prokinetics showed improvement in constipation, the one small RCT (n=15) showed no benefit. Osmotic laxative using Macrogol (1 RCT, n=57; 1 open label, n=8), fibre supplementation with psyllium (single-blind RCT, n=7) and secretagogue using lubiprostone (RCT, n= 52) demonstrated beneficial effects on constipation. The one open label study on levodopa (n=19) and the other one on probiotics (n=40) showed no effect.Figure 1Conclusion: This systematic review illustrates that studies assessing the effect of treatment agents on constipation in PD patients are lacking. Well-designed prospective RCT evaluating treatment options of constipation in PD patients are needed to optimize the symptomatic management in this challenging population.