10/28/05 11:53 AM
Melatonin May Reduce the Pain of Irritable Bowel Syndrome

Melatonin May Reduce the Pain of Irritable Bowel Syndrome

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

Release Date: October 14, 2005;

Oct. 14, 2005 — Melatonin may reduce the pain associated with irritable bowel syndrome (IBS), according to the results of a small, double-blind study reported in the October issue of Gut.

“Melatonin, a sleep promoting agent, is involved in the regulation of gastrointestinal [GI] motility and sensation,” write G. H. Song, MD, from the National University of Singapore, and colleagues. “In view of the high prevalence of sleep disturbance in IBS patients, and the possible double effects of melatonin in regulating sleep pattern and bowel function, we hypothesised that melatonin may be useful in the treatment of IBS, and its therapeutic effects might be most evident if it was used in IBS patients who suffer from concomitant sleep disturbance.”

In this study, 40 patients with IBS and sleep disturbances were randomized to receive either melatonin (3 mg) or matching placebo at bedtime for two weeks. There were 24 women and 16 men; age range was 20 to 64 years. Assessments immediately before and after treatment included patient-completed bowel, sleep, and psychological questionnaires; rectal manometry; and overnight polysomnography (PSG).

Compared with the placebo group, the melatonin group had a decreased mean abdominal pain score (2.35 vs 0.70; P < .001) and increased mean rectal pain threshold (8.9 vs -1.2 mm Hg; P < .01). Neither group had significant changes after treatment in bloating, stool type, stool frequency, or anxiety and depression scores nor in sleep parameters, including total sleep time, sleep latency, sleep efficiency, sleep onset latency, arousals, duration of stages 1 to 4, rapid eye movement (REM) sleep, and REM onset latency.

“Administration of melatonin 3 mg at bedtime for two weeks significantly attenuated abdominal pain and reduced rectal pain sensitivity without improvements in sleep disturbance or psychological distress,” the authors write. “The findings suggest that the beneficial effects of melatonin on abdominal pain in IBS patients with sleep disturbances are independent of its action on sleep disturbances or psychological profiles.”

Study limitations include small sample size, short treatment period, use of only one dose of melatonin, and limited sensitivity of the hospital anxiety and depression scale.

“Future studies should focus on therapy with different doses of melatonin, prolonging the treatment period, and using a larger sample size to provide a clearer view of the role of melatonin in IBS and sleep disturbance,” the authors conclude.

The authors have disclosed no financial relationships.

Gut. 2005;54:1402-1407

Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Describe the effect of two weeks of melatonin on abdominal pain and rectal pain sensitivity in IBS.
Describe the effect of two weeks of melatonin on sleep disturbances in IBS.
Clinical Context
Sleep disturbance is commonly observed in patients with IBS, occurring in 26% to 55%. Also, patients with IBS have more REM sleep characterized by arousal, according to the current authors. Melatonin is a close derivative of serotonin and is involved in the sleep-wake cycle via the pineal gland. The GI tract is another source of melatonin, which may exert excitatory and inhibitory effects regulating bowel motility. Melatonin may act by improving gut visceral hypersensitivity. The current authors postulated the melatonin supplementation may relieve bowel and sleep disturbances in patients with IBS with an effect on overall symptoms. This is a double-blind, randomized, placebo-controlled trial to examine the efficacy of 3 mg of melatonin once daily on IBS symptoms and sleep disturbances.

Study Highlights
Inclusion criteria were age 20 to 64 years with IBS diagnosis made by an experienced gastroenterologist using Rome II criteria and sleep disturbance, defined as difficulty getting to sleep, awakening at night, and early morning wakening.
Patients had a Pittsburgh sleep quality index (PSQI) score greater than 5 and sleep disturbance at least two nights a week for 12 weeks.
Exclusion criteria were pregnant or breast-feeding, organic GI, hepatic, or other systemic disorders, history of GI surgery, or cerebral disease.
At baseline an IBS symptom scale, hospital anxiety and depression scale, PSQI and Epsworth Sleepiness scale (ESS) were administered to assess bowel, sleep, and psychological functioning.
Patients also underwent rectal manometry to measure squeeze, push, and resting pressures; and overnight PSG at home, which included electroencephalogram, electrooculogram, nasal airflow pressure, electromyogram, and electrocardiogram.
These measures were repeated at the end of the study.
20 patients were randomized to receive 3 mg of melatonin orally at bedtime and 20 patients to identical-appearing placebo.
Mean age was 27 years, one third was men, and two thirds had the constipation or diarrhea subtype of IBS.
All patients completed the study. None reported adverse effects.
Abdominal pain score was significantly reduced in the melatonin vs the placebo group (2.35 vs 0.70; P < .001) after 2 weeks of treatment.
There was greater reduction in abdominal distension, stool frequency, and total bowel symptoms in the melatonin group.
There were no significant differences in stool type, abnormal sensation of defecation, or quality of life between the two groups.
Rectal distension pressures required to induce feelings of urgency and pain were significantly increased in the melatonin (from 18.4 - 23.0 mm Hg and from 24.8 - 33.7 mm Hg, respectively) vs the placebo group.
Distension pressure thresholds for the first sensation of distension or desire to defecate did not change or differ between the 2 groups.
There were no differences in rectal pressures during resting, pushing, or voluntary squeezing conditions between the 2 groups.
Sleep parameters including global PSQI score, sleep quality, latency, duration, efficiency, disturbance, use of sleep medications, and daytime dysfunction were not significantly different between the 2 groups.
ESS scores were similar between the 2 groups.
PSG findings for REM sleep, onset latency, arousal index, and amount of REM vs non-REM sleep were similar between the 2 groups.
Pearls for Practice
Use of 3 mg of melatonin once daily for two weeks in IBS patients is associated with improvement in bowel pain and rectal distension thresholds for urgency and pain but not with a change in stool frequency, type, or quality of life.
Melatonin at 3 mg daily for two weeks is not associated with improvement in sleep disturbance.

Medscape Medical News 2005. © 2005 Medscape


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