Megan Brooks

June 21, 2010

June 21, 2010 (Buenos Aires, Argentina) — By augmenting rectal contraction and easing paradoxical sphincter contraction on defecation, levodopa ameliorates anorectal constipation in patients with de novo Parkinson's disease (PD).

That's according to a late-breaking study presented at the Movement Disorder Society 14th International Congress of Parkinson's Disease and Movement Disorders.

"Although dopamine has been believed to be 'no good' for bowel function, the study result strongly suggests that levodopa is 'good' for early-stage PD patients," study presenter Ryuji Sakakibara, MD, PhD, associate professor of neurology and internal medicine at Sakura Medical Center, Toho University, Tokyo, Japan, noted in an email to Medscape Neurology. "This is a novel finding that has not been studied both subjectively and objectively."

QL-GAT Study

Using the quantitative lower-gastrointestinal autonomic test (QL-GAT), Dr. Sakakibara and colleagues examined levodopa's effects on anorectal constipation in 19 unselected de novo PD patients. Their mean age was 66 years, and mean duration of disease was 2.2 years. On the basis of responses to a standard questionnaire, all but 1 patient had constipation.

Patients were treated with levodopa (200 mg/d) and carbidopa (20 mg/d) for 3 months. After treatment, 16 of the 19 patients reported improvements in bowel frequency and defecation, Dr. Sakakibara noted.

On the basis of the QL-GAT, levodopa did not produce any significant change in colonic transit time of the total colon or any segment of the colon.

"During rectal filling, levodopa significantly lessened the first sensation (P < .05). It also tended to augment the amplitude in rectal constipation, although these changes failed to reach statistical significance," the study authors report in a meeting abstract.

During defecation, levodopa significantly lessened the amplitude in paradoxical sphincter contraction on defecation (P < .01), they report, and tended to augment the amplitude in rectal contraction and lessen the amplitude of abdominal strain, although these changes did not reach statistical significance. Overall, levodopa significantly lessened postdefecation residuals (P < .05).

On the basis of these findings and studies in mice, levodopa "might act on lower gastrointestinal tract function by both enteric nervous system and central nervous system mechanisms," Dr. Sakakibara and colleagues say.

Frequent and Troublesome Feature

In a written statement from the meeting, Ronald Pfeiffer, MD, of the University of Tennessee Health Science Center, Memphis, who was not involved in the study, noted that bowel dysfunction is a "frequent and sometimes very troublesome nonmotor feature of Parkinson's disease that may include both decreased bowel movement frequency due to slowed colonic motility and difficulty with the act of defecation itself due to anorectal dysfunction.

"While a number of treatment modalities are useful in improving bowel movement frequency, effective treatment of anorectal dysfunction has been much more elusive," Dr. Pfeiffer added. "The QL-CAT study, reported by Dr. Sakakibara and colleagues, documents for the first time that levodopa is effective in improving rectal function in patients with Parkinson's disease.

"This study," he concludes, "should prompt further investigation into additional treatment approaches involving dopaminergic mechanisms that might be even more effective in ameliorating this troublesome aspect of Parkinson's disease."

Christopher G. Goetz, MD, director of the Movement Disorders Program at Rush University Medical Center, Chicago, Illinois, and a member of the Movement Disorder Society, who was not involved in the study, added in an email to Medscape Neurology: "A clear definition of the role of Parkinson's disease itself versus levodopa has important implications in terms of understanding treatments that could have a positive impact on constipation."

Dr. Sakakibara, Dr. Pfeiffer, and Dr. Goetz have disclosed no relevant financial relationships.

Presented at the Movement Disorder Society 14th International Congress of Parkinson's Disease and Movement Disorders: Abstract LB-01. Presented June 16, 2010.

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