MANAGEMENT OF SLOW COLONIC TRANSIT CONSTIPATION IN PARKINSON'S DISEASE: CURRENT EVIDENCE AND A COMMUNITY PHARMACY PERSPECTIVE
Keywords:Constipation, Nil, Treatment, Non-motor, Pharmacy practice
The non-motor symptoms of Parkinson's disease are often under-recognised and undertreated. Constipation is exceedingly common in Parkinson's disease, reportedly affecting up to 70% of patients. Pharmacists are ideally positioned to screen patients with Parkinson's disease for constipation and to optimise constipation management. This review will describe the evidence base for the use of different treatments in the management of constipation in patients with Parkinson's disease. PubMed, Embase and Web of Science were searched using the following search terms: "constipation" OR "gastrointestinal dysfunction" OR "slow colonic transit" OR "defecatory dysfunction" OR "slow motility" AND "treatment" OR "management" OR "therapy" AND "Parkinson* disease". The literature indicates macrogol is a safe and effective treatment for constipation in Parkinson's disease; it should be considered a first line treatment and can be recommended by the pharmacist over-the-counter. Pharmacists can provide information regarding fibre supplementation with psyllium, which may be effective and can be initiated early. Lubiprostone appears to be a promising option, but larger and longer trials are warranted. Although many commonly employed treatments for constipation have not been evaluated for efficacy in Parkinson's disease, pharmacists can utilise available data to make evidence-based recommendations to optimise management of constipation and improve patient quality of life.
Keywords: Constipation, Parkinson's disease, Treatment, Non-motor, Pharmacy practice
Martinez-Martin P. The importance of non-motor disturbances to quality of life in Parkinson's disease. J Neurol Sci 2011;310:12-6.
Pfeiffer RF, Quigley EM. Gastrointestinal motility problems in patients with Parkinsonâ€™s disease. CNS Drugs 1999;11:435-48.
Rahman M, Uddin M, Chowdhury J, Chowdhury T. Effect of levodopa and carbidopa on non-motor symptoms and signs of Parkinson's disease. Mymensingh Med J 2014;23:18-23.
Ramjit AL, Sedig L, Leibner J, Wu SS, Dai Y, Okun MS, et al. The relationship between anosmia, constipation, and orthostasis and Parkinson's disease duration: results of a pilot study. Int J Neurosci 2010;120:67-70.
Sakakibara R, Shinotoh H, Uchiyama T, Sakuma M, Kashiwado M, Yoshiyama M, et al. Questionnaire-based assessment of pelvic organ dysfunction in Parkinson's disease. Auton Neurosci 2001;92:76-85.
Wang CP, Sung WH, Wang CC, Tsai PY. Early recognition of pelvic floor dyssynergia and colorectal assessment in Parkinson's disease associated with bowel dysfunction. Colorectal Disease 2013;15:e130-7.
Soykan I, Lin Z, Bennett JP, McCallum RW. Gastric myoelectrical activity in patients with Parkinson's disease: evidence of a primary gastric abnormality. Dig Dis Sci 1999;44:927-31.
Braak H, de Vos RA, Bohl J, Del Tredici K. Gastric Î±-synuclein immunoreactive inclusions in meissner's and auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett 2006;396:67-72.
Cersosimo MG, Benarroch EE. Neural control of the gastrointestinal tract: implications for Parkinson disease. Mov Disord 2008;23:1065-75.
Cersosimo MG, Raina GB, Pecci C, Pellene A, Calandra CR, Gutierrez C, et al. Gastrointestinal manifestations in Parkinson's disease: prevalence and occurrence before motor symptoms. J Neurol 2013;260:1332-8.
Lebouvier T, Chaumette T, Damier P, Coron E, Touchefeu Y, Vrignaud S, et al. Pathological lesions in colonic biopsies during Parkinsonâ€™s disease. Gut 2008;57:1741-3.
Wakabayashi K, Takahashi H, Takeda S, Ohama E, Ikuta F. Parkinson's disease: the presence of lewy bodies in auerbach's and meissner's plexuses. Acta Neuropathol 1988;76:217-21.
Annerino DM, Arshad S, Taylor GM, Adler CH, Beach TG, Greene JG. Parkinsonâ€™s disease is not associated with gastrointestinal myenteric ganglion neuron loss. Acta Neuropathol 2012; 124:665-80.
Singaram C, Ashraf W, Gaumnitz EA, Torbey C, Sengupta A, Pfeiffer R, et al. Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation. Lancet 1995;346:861-4.
Koller W, Lees A, Doder M, Hely M. Randomized trial of tolcapone versus pergolide as addâ€on to levodopa therapy in Parkinson's disease patients with motor fluctuations. Mov Disord 2001;16:858-66.
MÃ¼ller B, Assmus J, Larsen J, Haugarvoll K, Skeie G, Tysnes OB. Autonomic symptoms and dopaminergic treatment in de novo Parkinson's disease. Acta Neurol Scand 2013;127:290-4.
Abbott R, Petrovitch H, White L, Masaki K, Tanner C, Curb J, et al. Frequency of bowel movements and the future risk of Parkinsonâ€™s disease. Neurology 2001;57:456-62.
Soler J, Denys P, Game X, Ruffion A, Chartier-Kastler E. Anal incontinence and gastrointestinal disorders and their treatment in neurourology. Prog Urol 2007;17:622-8.
Brading AF, Ramalingam T. Mechanisms controlling normal defecation and the potential effects of spinal cord injury. Prog Brain Res 2006;152:345-58.
Holstege G, Tan J. Supraspinal control of motoneurons innervating the striated muscles of the pelvic floor including urethral and anal sphincters in the cat. Brain 1987;110:1323-44.
VanderHorst VG, Samardzic T, Saper CB, Anderson MP, Nag S, Schneider JA, et al. Î±â€synuclein pathology accumulates in sacral spinal visceral sensory pathways. Ann Neurol 2015;78:142-9.
Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003;24:197-211.
Ueki A, Otsuka M. Life style risks of Parkinsonâ€™s disease: association between decreased water intake and constipation. J Neurol 2004;251:vii18-23.
Hawkes CH, Del Tredici K, Braak H. A timeline for Parkinson's disease. Parkinsonism Relat Disord 2010;16:79-84.
Toebosch S, Tudyka V, Masclee A, Koek G. Treatment of recurrent sigmoid volvulus in Parkinson's disease by percutaneous endoscopic colostomy. World J Gastroenterol 2012;18:5812.
Shimada J, Sakakibara R, Uchiyama T, Liu Z, Yamamoto T, Ito T, et al. Intestinal pseudoâ€obstruction and neuroleptic malignant syndrome in a chronically constipated parkinsonian patient. Eur J Neurol 2006;13:306-7.
Elliot D, Watts W, Girard D. Constipation. Mechanisms and management of a common clinical problem. Postgrad Med J 1983;74:143-9.
Noguera A, Centeno C, Librada S, Nabal M. Screening for constipation in palliative care patients. J Palliative Med 2009;12:915-20.
Rome F. Guidelines-Rome III diagnostic criteria for functional gastrointestinal disorders. J Gastrointestin Liver Dis 2006;15:307.
Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis 2006;15:237.
Australia Pso. Australian pharmaceutical formulary and handbook 23. 23rd ed. ed. L. Sansom: Pharmaceutical society of Australia; 2015.
Nutrient Reference Values for Australia and New Zealand; 2014. Available from: https://www.nrv.gov.au/nutrients/ dietary-fibre. [Last accessed on 26 Feb 2016].
Rutter P. Community pharmacy: symptoms, diagnosis and treatment: Elsevier Health Sciences; 2013.
Jost W, Schimrigk K. Cisapride treatment of constipation in Parkinson's disease. Mov Disord 1993;8:339-43.
Young RJ, Beerman LE, Vanderhoof JA. Increasing oral fluids in chronic constipation in children. Gastroenterol Nurs 1998;21:156-61.
Anti M, Lamazza A, Pignataro G, Pretaroli A, Armuzzi A, Pace V, et al. Water supplementation enhances the effect of high-fiber diet on stool frequency and laxative consumption in adult patients with functional constipation. Hepatogastroenterology 1998;45:727-32.
Lindeman RD, Romero LJ, Liang HC, Baumgartner RN, Koehler KM, Garry PJ. Do elderly persons need to be encouraged to drink more fluids? J Gerontol A Biol Sci Med Sci 2000;55:M361-5.
MÃ¼ller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol 2005;100:232-42.
Astarloa R, Mena M, Sanchez V, De La Vega L, De Yebenes J. Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease. Clin Neuropharmacol 1992;15:375-80.
Ashraf W, Pfeiffer RF, Park F, Lof J, Quigley EM. Constipation in Parkinson's disease: objective assessment and response to psyllium. Mov Disord 1997;12:946-51.
De Schryver AM, Keulemans YC, Peters HP, Akkermans LM, Smout AJ, De Vries WR, et al. Effects of regular physical activity on defecation pattern in middle-aged patients complaining of chronic constipation. Scand J Gastroenterol 2005;40:422-9.
Everhart JE, Go VL, Johannes RS, Fitzsimmons SC, Roth HP, White LR. A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci 1989;34:1153-62.
Fertl E, Doppelbauer A, Auff E. Physical activity and sports in patients suffering from Parkinson's disease in comparison with healthy seniors. J Neural Transm Parkinson's Dis Dementia Sect 1993;5:157-61.
van Nimwegen M, Speelman AD, Hofman-van Rossum EJ, Overeem S, Deeg DJ, Borm GF, et al. Physical inactivity in Parkinson's disease. J Neurol 2011;258:2214-21.
Speelman AD, van de Warrenburg BP, van Nimwegen M, Petzinger GM, Munneke M, Bloem BR. How might physical activity benefit patients with Parkinson disease? Nat Rev Neurol 2011;7:528-34.
Bryant MS, Rintala DH, Hou JG, Protas EJ. Relationship of falls and fear of falling to activity limitations and physical inactivity in Parkinson's disease. J Aging Phys Act 2015;23:187-93.
Cassani E, Privitera G, Pezzoli G, Pusani C, Madio C, Iorio L, et al. Use of probiotics for the treatment of constipation in Parkinson's disease patients. Minerva Dietol Gastroenterol 2011;57:117-21.
Gabrielli M, Bonazzi P, Scarpellini E, Bendia E, Lauritano EC, Fasano A, et al. Prevalence of small intestinal bacterial overgrowth in Parkinson's disease. Mov Disord 2011;26:889-92.
Fasano A, Bove F, Gabrielli M, Petracca M, Zocco MA, Ragazzoni E, et al. The role of small intestinal bacterial overgrowth in Parkinson's disease. Mov Disord 2013;28:1241-9.
Tan AH, Mahadeva S, Thalha AM, Gibson PR, Kiew CK, Yeat CM, et al. Small intestinal bacterial overgrowth in Parkinson's disease. Parkinsonism Relat Disord 2014;20:535-40.
Rossi S. ed. Australian Medicines Handbook. Australian Medicines Handbook Ltd Pty: Adelaide; 2016.
Eichhorn TE, Oertel WH. Macrogol 3350/electrolyte improves constipation in Parkinson's disease and multiple system atrophy. Mov Disord 2001;16:1176-7.
Zangaglia R, Martignoni E, Glorioso M, Ossola M, Riboldazzi G, Calandrella D, et al. Macrogol for the treatment of constipation in Parkinson's disease. A randomized placeboâ€controlled study. Mov Disord 2007;22:1239-44.
Coggrave M, Norton C, Cody JD. Management of faecal incontinence and constipation in adults with central neurological diseases. Cochrane Database Syst Rev 2014;1. Doi:10.1002/14651858.CD002115. [Article in Press]
Freedman MD, Schwartz HJ, Roby R, Fleisher S. Tolerance and efficacy of polyethylene glycol 3350/Electrolyte solution versus lactulose in relieving opiate induced constipation: a doubleâ€blinded placeboâ€controlled trial. J Clin Pharmacol 1997;37:904-7.
Mueller-Lissner S, Wald A. Constipation in adults. Br Med J 2010;7:413-38.
Rossi M, Merello M, Perez-Lloret S. Management of constipation in Parkinson's disease. Expert Opin Pharmacother 2015;16:547-57.
Gattuso J, Kamm M. Adverse effects of drugs used in the management of constipation and diarrhoea. Drug Saf 1994;10:47-65.
Bird MR, Woodward MC, Gibson EM, Phyland DJ, Fonda D. Asymptomatic swallowing disorders in elderly patients with Parkinson's disease: a description of findings on clinical examination and videofluoroscopy in sixteen patients. Age Aging 1994;23:251-4.
Jost W, Schimrigk K. The effect of cisapride on delayed colonic transit time in patients with idiopathic Parkinson's disease. Wien Klin Wochenschr 1994;106:673-6.
Jost WH. Gastrointestinal motility problems in patients with Parkinsonâ€™s disease. Drugs Aging 1997;10:249-58.
Quigley EM. Cisapride: What can we learn from the rise and fall of a prokinetic? J Dig Dis 2011;12:147-56.
Morgan JC, Sethi KD. Tegaserod in constipation associated with Parkinson disease. Clin Neuropharmacol 2007;30:52-4.
Sullivan KL, Staffetti JF, Hauser RA, Dunne PB, Zesiewicz TA. Tegaserod (Zelnorm) for the treatment of constipation in Parkinson's disease. Mov Disord 2006;21:115-6.
Liu Z, Sakakibara R, Odaka T, Uchiyama T, Uchiyama T, Yamamoto T, et al. Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients. Mov Disord 2005;20:680-6.
Unknown. Prucalopride: a guide to its use in chronic constipation. Drug Ther Perspect 2010;26:1-4.
Mozaffari S, Didari T, Nikfar S, Abdollahi M. Phase II drugs under clinical investigation for the treatment of chronic constipation. Expert Opin Invest Drugs 2014;23:1485-97.
Soykan I, Sarosiek I, Shifflett J, Wooten GF, McCallum RW. Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with Parkinson's disease. Mov Disord 1997;12:952-7.
Lertxundi U, Domingo-Echaburu S, Soraluce A, Garcia M, Ruiz-Osante B, Aguirre C. Domperidone in parksinson's disease: a perilous arrhythmogenic or the gold standard? Curr Drug Saf 2013;8:63-8.
Lacy BE, Chey WD. Lubiprostone: chronic constipation and irritable bowel syndrome with constipation. Expert Opin Pharmacother 2009;10:143-52.
Ueno R, Osama H, Habe T, Engelke K, Patchen M. Oral SPI-0211 increases intestinal fluid secretion and chloride concentration without altering serum electrolyte levels. Gastroenterology 2004;126:A298.
Ondo W, Kenney C, Sullivan K, Davidson A, Hunter C, Jahan I, et al. Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease. Neurology 2012;78:1650-4.
Lembo AJ, Schneier HA, Shiff SJ, Kurtz CB, MacDougall JE, Jia XD, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med 2011;365:527-36.
Barboza J, Okun MS, Moshiree B. The treatment of gastroparesis, constipation and small intestinal bacterial overgrowth syndrome in patients with Parkinson's disease. Expert Opin Pharmacother 2015;16:2449-64.
Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, et al. The PRIAMO study: a multicentre assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord 2009;24:1641-9.
Sandyk R, Gillman M. Colchicine ameliorates constipation in Parkinson's disease. J R Soc Med 1984;77:1066.
Sadjadpour K. Pyridostigmine bromide and constipation in Parkinson's disease. JAMA 1983;249:1148.
Sakakibara R, Sato M, Hirai S, Masaka T, Kishi M, Tsuyusaki Y, et al. Nizatidine ameliorates slow transit constipation in parkinson's disease. J Am Geriatr Soc 2015;63:399-401.
Pagano G, Tan EE, Haider JM, Bautista A, Tagliati M. Constipation is reduced by beta-blockers and increased by dopaminergic medications in Parkinson's disease. Parkinsonism Relat Disord 2015;21:120-5.
Sakakibara R, Odaka T, Lui Z, Uchiyama T, Yamaguchi K, Yamaguchi T, et al. Dietary herb extract Daiâ€kenchuâ€to ameliorates constipation in parkinsonian patients (Parkinson's disease and multiple system atrophy). Mov Disord 2005;20:261-2.
Hashimoto K, Satoh K, Kase Y, Ishige A, Kubo M, Sasaki H, et al. Modulatory effect of aliphatic acid amides from Zanthoxylum piperitum on isolated gastrointestinal tract. Planta Med 2001;67:179-81.
Satoh K, Hayakawa T, Kase Y, Ishige A, Sasaki H, Nishikawa S, et al. Mechanisms for contractile effect of Dai-kenchu-to in isolated guinea pig ileum. Dig Dis Sci 2001;46:250-6.
Ogawa E, Sakakibara R, Kishi M, Tateno F. Constipation triggered the malignant syndrome in Parkinson's disease. Neurol Sci 2012;33:347-50.
Kawahara H, Mitani Y, Nomura M, Nose K, Yoneda A, Hasegawa T, et al. Impact of rikkunshito, an herbal medicine, on delayed gastric emptying in profoundly handicapped patients. Pediatr Surg Int 2009;25:987-90.
Doi H, Sakakibara R, Sato M, Hirai S, Masaka T, Kishi M, et al. Dietary herb extract rikkunshi-to ameliorates gastroparesis in Parkinson's disease: a pilot study. Eur Neurol 2014;71:193-5.