1Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
2Mah Pooi Soo & Tan Chin Nam Centre for Parkinson’s & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
3Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
4Department of Medicine, Hospital Pulau Pinang, Penang, Malaysia
Copyright © 2023 The Korean Movement Disorder Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Conflicts of Interest
The authors have no financial conflicts of interest.
Funding Statement
None
Author Contributions
Conceptualization: Ai Huey Tan. Data curation: Ai Huey Tan, Kee Huat Chuah, Yuan Ye Beh, Jie Ping Schee. Supervision: Ai Huey Tan, Kee Huat Chuah, Sanjiv Mahadeva, Shen-Yang Lim. Visualization: Ai Huey Tan, Yuan Ye Beh, Jie Ping Schee. Writing—original draft: Ai Huey Tan, Kee Huat Chuah. Writing—review & editing: all authors.
Class | Prokinetics | Clinical evidence in PD and important notes for clinical practice |
---|---|---|
Dopamine (D2) receptor antagonist | Domperidone* (does not cross blood- brain-barrier [BBB]) | Improve GE time and gastroparesis symptom scores in PD patients in an open-label study (n = 17). [61] |
Increase levodopa bioavailability in PD patients in a cross-over study (n = 18). [62] | ||
There are concerns regarding risk of cardiac arrhythmias; recent studies demonstrated good safety profile in patients without pre-existing heart disease, and when taking ≤ 30 mg daily. | ||
Serotonin (5-HT4) receptor agonists | Mosapride; Prucalopride | Improve GE time in PD patients in two small open-label studies (n = 5–10). [63,64] |
Histamine (H2) receptor antagonist | Nizatidine | Improve GE time in PD patients in a small open-label study (n = 20). [65] |
Ghrelin receptor agonist | Relamorelin | Shown to be an effective treatment for diabetic gastroparesis in several well-designed clinical trials. |
Evidence in PD remains limited. | ||
Motilin receptor agonist | Erythromycin; Azithromycin | Extended use not appropriate due to risk of cardiac arrythmias, drugs interactions and anti-microbial activities. |
Camicinal* | Improve levodopa absorption and motor fluctuations in PD patients with a non-significant trend in improving GE time vs. placebo, after 8 days of treatment, in a DB-RCT (n = 58). [66] | |
Multi-action prokinetics | DA-9701* | Improve GE time in PD patients and was non-inferior vs. domperidone, with no significant difference in levodopa bioavailability, after 4 weeks of treatment, in a DB-RCT (n = 35). [67] |
Improve upper GI symptom scores and GI-related quality of life vs. placebo in PD patients, without worsening of parkinsonian symptoms, after 12 weeks of treatment, in a DB-RCT (n = 144). [41] |
Class | Agent | Clinical evidence in PD and important notes for clinical practice |
---|---|---|
Fibre | Fibre tablet | Improve BM frequency (from < 2 BM/week at baseline to at least 4 BM/week), levodopa bioavailability and UPDRS scores in one small open label study (n = 19). [122] |
Psyllium | Improve diary-recorded BM frequency (from ≈ 2.9 BM/week at baseline to ≈ 5.8 BM/week) in one small DB-RPCT (n = 7), with no significant changes in colonic transit study and anorectal manometry. [123] | |
Osmotic laxatives | Macrogol* | Improve self-reported BM frequency (from < 2 to one BM every second week at baseline to 2–4 BM/week) in one small open-label study (n = 8) [124] |
Improve diary-recorded BM frequency (from ≈ 1.9 BM/week to ≈ 6.6 BM/week) as recorded by stool diary, stool consistency and straining in one DB-RPCT (n = 57). [125] | ||
Prosecretory agents | Lubiprostone* | Improve diary-recorded BM frequency (from ≈ 0.8 BM/week at baseline to ≈ 1.0 BM/week), visual analog scale score and patient subjective impression of change in one DB-RPCT (n = 54). [126] |
Linaclotide | Improve self-reported BM frequency (from ≈ 1 BM/week at baseline to ≈ 3 BM/week) in a retrospective record review; subjective improvement was documented in 10 out of 16 patients. [127] Interestingly, in patients who did not respond to prucalopride, 67% reported improvement after switching to linaclotide. [127] | |
Serotonergic (5-HT4) receptor agonist* | Mosapride | Subjective improvement in BM frequency and difficult defecation, with shortened colonic transit time and augmentation of rectal contraction in one small open-label study. [128] |
Prucalopride | Improve self-reported BM frequency (from ≈ 1 BM/week to ≈ 5 BM/week) in a retrospective record review; subjective improvement was documented in 6 out of 13 patients. [127] | |
Ghrelin receptor agonist | Relamorelin | Recruitment goals (target sample size = 56) of one DB-RPCT were not met. No significant clinical benefits detected with treatment, likely compromised by the limited power of the study. [129] |
Probiotics* | Diet therapy and fermented milk containing Lactobacilus shirota | Improve diary-recorded frequency of BM with normal stool consistency, and constipation-associated bloatedness, sense of incomplete emptying and abdominal pain in one small open-label study (n = 40). [130] |
Fermented milk containing multi-strain probiotic (i.e., Streptococcus salivarius subsp thermophilus, Enterococcus faecium, Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp bulgaricus, Bifidobacterium breve, and Bifidobacterium animalis subsp lactis) and prebiotic fiber | Improve diary-recorded complete BM frequency (mean increase of 1.2 BM/week), stool consistency, and reduce laxative use in one DB- RPCT (n = 120). [131] | |
Fermented milk containing multi-strain probiotic (i.e., Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus lactis, Bifidobacterium infantis, and Bifidobacterium longum) | Improvement in self-reported BM frequency (from ≈ 2.1 BM/week to ≈ 4.2 BM/week) with shortened colonic transit time in one DB-RPCT (n = 48). [132] | |
Multi-strain probiotics capsules (i.e., Enterococcus faecium, Enterococcus feacalis, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus gasseri, and Lactobacillus reuteri) | Improve diary-recorded spontaneous BM frequency (mean increase of 1.0 BM/week), stool consistency and quality of life related to constipation in one DB-RPCT (n = 72). [133] | |
Powdered probiotics sachet containing Bifidobacterium animalis subsp. lactis | Improve self-reported spontaneous (from ≈ 3.1 BM/week to ≈ 4.2 BM/ week) and complete BM frequency (from ≈ 1.4 BM/week to ≈ 3.3 BM/ week) and stool consistency, sleep quality and anxiety in one DB-RPCT (n = 72). [134] | |
Multi-strain probiotics capsules (i.e., Bacillus licheniformis, Lactobacillus acidophilus, Bifidobacterium longum, and Enterococcus faecalis) | Improve self-reported complete BM frequency and stool consistency in one DB-RPCT (n = 46). [135] | |
Squalamine phosphate | ENT-01* | Improve complete spontaneous BM frequency (from ≈ 1.2 BM/week to ≈ 3.6 BMs/week), stool consistency and quality of life related to constipation in one small open-label trial (n = 34). [136] |
Improve complete spontaneous BM frequency (from ≈ 0.7 BM/week to ≈ 3.2 BMs/week) and stool consistency, but not quality of life related to constipation in one DB-RPCT (n = 150). [137] | ||
Herbal/plant extract | Dai-Kenchu-To | Subjectived improvement in BM frequency, with shortened colonic transit time and augmentation of rectal contraction in one small open- label study (n = 6). [138] |
STW5 | Improve stool consistency, but not BM frequency in one small open- label study (n = 44). [139] | |
PHGG+ | Minimal improvement in constipation severity score in one small open- label study (n = 34) [140] |