Constipation is a common condition in patients with neurodegenerative parkinsonism , which includes Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).
Multiple mechanisms of pathogenesis have been proposed, such as the accumulation of α-synuclein in the gastrointestinal system, dysautonomia, and drug side effects.
Chronic constipation negatively affects quality of life and decreases the absorption of antiparkinsonian drugs.
Conventional treatment, including adequate fiber and fluid intake and over-the-counter laxatives, are generally ineffective.
Linaclotide (guanylate cyclase C agonist) and prucalopride (selective 5-HT4 receptor agonist) are emerging effective drugs for the treatment of chronic idiopathic constipation (CIC). To date, these drugs have not been tested in controlled trials in patients with parkinsonism and, therefore, their effectiveness is unknown in this population.
With approval from a local ethics committee, we searched our database for patients diagnosed with neurodegenerative parkinsonism and constipation who had received linaclotide or prucalopride.
Constipation was defined according to the Rome III criteria and one of the symptoms must include less than three bowel movements (BM) per week. Patients who had undergone prior small or large bowel surgery were excluded, except for percutaneous endoscopic gastrostomy placement.
Demographics, treatment characteristics, frequency of BM, and side effects were captured from medical records. Objective improvement was defined as the frequency of posttreatment BMs of three or more per week.
Subjective improvement was assessed by clinical or telephone interview, and the level of patient satisfaction was defined as “agreement” or “strong agreement” with the study drug treating constipation symptoms. Results were captured on a five-point Likert scale.
- Among the 30 patients identified, 13 received only linaclotide, 11 received only prucalopride, and six people used both drugs, but not simultaneously.
- The mean duration of treatment with linaclotide (145 or 290 μg) was 10 ± 8 months and with prucalopride (1-4 mg) was 19 ± 18 months.
- The number of bowel movements (BM) per week increased significantly after treatment with linaclotide (1.5 [1–3] vs. 3 [2–7]; P < 0.01) or prucalopride (1 [1–2] vs. 5 [2–7]). 1–7]; P < 0.05).
- In patients who did not respond to prucalopride, 67% reported improvement after switching to linaclotide.
- Subjective satisfaction with treating their constipation symptoms was higher for patients receiving linaclotide than prucalopride (69% vs. 47%).
- The proportion of objective and subjective improvement was not significantly different between patients with Parkinson’s disease (PD) and without PD.
- There were no differences in the use of over-the-counter laxatives before starting treatment in both groups.
- Side effects were only reported in one patient who discontinued prucalopride due to headache.
Linaclotide and prucalopride are effective, safe and well tolerated in patients with Constipation in Patients with Parkinsonism.
Both drugs improved bowel movement (BM) frequency in our patients with neurodegenerative parkinsonism who had failed initial constipation management.
Interestingly, a greater proportion of patients reported subjective satisfaction in controlling their constipation symptoms with the use of linaclotide compared to prucalopride.
While recall bias and missing data in this retrospective study limit our ability to make a definitive recommendation, our preliminary results suggest potential benefits of these medications and we therefore encourage other well-designed controlled trials to advance the standard of care. care of constipation in patients with parkinsonism.
