Laxative use tied to slowing of rigidity progression in Parkinson's disease

Last Updated: 2016-05-30

By Will Boggs MD

NEW YORK (Reuters Health) - Maintenance laxative use is associated with a slowing of the progression of Parkinson's disease rigidity, researchers from the U.K. report.

"This adds to our indicative evidence of a continuing role of gastrointestinal dysbiosis in the pathogenesis of Parkinson's disease," Dr. Sylvia M. Dobbs from King's College London told Reuters Health by email. "It also points to a potential new approach to the management of rigidity, using these classes of on-the-shelf-medication, under medical supervision."

Constipation often predates the diagnosis of Parkinson's disease by decades, and it markedly affects the quality of life in patients with Parkinson's disease, Dr. Dobbs and colleagues note in the British Journal of Clinical Pharmacology, online May 21.

Extensive earlier work by the researchers led them to hypothesize that maintenance laxative therapy for constipation might ameliorate rigidity. They tested this retrospectively in a service evaluation of objectively measured rigidity in 79 Parkinson's disease patients attending a gut-brain axis clinic over 374 person-years.

Prior to receiving maintenance laxatives, patients experienced an average 5.5% annual increase in flexor rigidity. Flexor rigidity plateaued, however, after maintenance laxatives were introduced.

The apparent stemming of progression was similar for bulk, osmotic, and enterokinetic laxative classes, and there were no important interactions between laxative and antiparkinsonian medication on flexor rigidity.

There were no significant changes in extensor rigidity, neither before nor after introduction of maintenance laxatives, the researchers found.

In contrast, flexor rigidity decreased by 18.7% and extensor rigidity decreased by 15.7% within a median 4.5 months of exposure to linaclotide, a guanylate cyclase-C receptor agonist approved for the treatment of chronic idiopathic constipation and constipation-predominant irritable bowel syndrome.

"This retrospective service evaluation is analogous to an intention-to-treat, open intervention study over years, albeit that the laxatives were intended to treat constipation not rigidity," Dr. Dobbs explained. "A limitation is the lack of a randomized comparator. Since slow gastrointestinal-transit is intrinsic to Parkinson's disease, a parallel arm without laxatives is not a long-term option."

"The immediate therapeutic implication is that maintenance laxatives are disease-modifying in Parkinson's disease," the researchers concluded. "Actively and meticulously managed, tailored maintenance laxative schedules within fixed protocols, compared with standard clinical care of prn laxatives, is a potential tool for exploring the effect of exposome drivers and immuno-inflammatory and metabolomic mediators on objectively measured flexor rigidity."

SOURCE: http://bit.ly/1TSiDCZ

Br J Clin Pharmacol 2016.