Rosman et al. 2008; USA
PEDro = 8
RCT with crossover
N = 7

Population: 7 SCI subjects with defecatory problems (age 46.9 + 3.4 yrs, range 30 – 56 yrs).
Treatment: injections of neostigmine/ glycopyrrolate for 1 week, wash-out period for 1 week, and placebo for 1 week, in random order
Outcome Measures: Total bowel evacuation time; time to first flatus; time to beginning of stool flow; time to end of stool flow.

1. Compared with placebo, neostigmine/glycopyrrolate significantly reduced the total bowel evacuation time from 98.1 + 7.2 min to 74.8 + 5.8 min
2. Neostigmine/glycopyrrolate significantly reduced the time to first flatus from 56.9 + 5.4 min to 21.8 + 4.5 min
3. Neostigmine/glycopyrrolate also significantly reduced the time to beginning of stool flow from 69.8 ± 2.8 to 42.3 ± 6.4 min, and time to end of stool flow from 80.3 ± 4.0 to 53.3 ± 8.3 min.

Geders et al. 1995; USA
PEDro = 8
RCT
N=9

Population: mean age range: treatment group - 58.8 years, controls - 63.4 years, 2 subjects with paraplegia, 7 subjects with tetraplegia
Treatment: Cisapride or placebo administered in oral doses. Subjects received cisapride or placebo 3 days before ingestion of the radiopque markers. 
Outcome Measures: total and segmental colonic transit time (CTT), questionnaire on type, frequency, and severity of clinical symptoms before and after cisapride or placebo administration

1. Mean total colonic transit time (CTT) was significantly longer in SCI patients than controls.
2. Subjects with a normal CTT demonstrated no benefit to the administration of cisapride.
3. 5 subjects with tetraplegia with initial abnormal total CTT improved their left CTT following treatment
4. No adverse side effects of cisapride administration were noted.

Rajendran et al. 1992; USA
PEDro = 8
RCT
N=14

Population: Age range: 19-71yrs, Level of injury: C4-L2; 7 subjects with tetraplegia and 7 subjects with paraplegia; length of injury range=7 months-33yrs.
Treatment: Subjects were administered cisapride orally (10mg four times a day) for 4d. Gastric emptying or mouth-to-cecum transit time (MCTT) was measured either on the 4th or 5th day after the administration of cisapride or placebo. The control subjects were tested without medication or placebo.
Outcome Measures: MCTT; gastric emptying

1. No delay or improvement in gastric emptying was observed after the administration of cisapride.
2. Mean MCTT in subjects with tetraplegia was significantly longer than normal subjects; cisapride resulted in normalization of the MCTT among the subjects with tetraplegia.

Krogh et al. 2002; Denmark
PEDro = 7
RCT
N=22

Population: mean age: 34.7±2.49 yrs (placebo), 36.5±3.91 yrs (1mg group),  44.3±3.05 yrs (2mg group)
Treatment: Subjects randomized to double-blind treatment with prucalopride 1mg or placebo, taken 1/day for 4 wks. A 2nd group of subjects was randomized to double-blind treatment with prucalopride 2mg or placebo for 4wks.
Outcome measures: constipation; urinary habit; constipation severity and symptoms; colonic transit times

1. Compared with baseline, mean changes in constipation severity increased with placebo, but decreased with prucalopride.
2. Diary data showed an improvement in average weekly frequency of all bowel movements over 4 wks within the 2 mg group.
3. 4 subjects (2 mg group) reported moderate/severe abdominal pain.

Korsten et al. 2005; USA
PEDro = 6
RCT
N=13

Population: 5 subjects with tetraplegia and 8 with paraplegia; Age: mean 46 years, range 25-69; TSI: mean 14 years, range 1-31; Type of injury: All motor complete except 1, 8 sensory incomplete, 5 sensory complete; Level of injury: C4-T12
Treatment: On separate days, subjects received, in a randomized, blinded design, one of three intravenous infusates (normal saline, 2 mg neostigmine, or 2 mg neostigmine + 0.4 mg glycopyrrolate).
Outcome Measures: The effect of these infusates on bowel evacuation of barium paste.

1. Neostigmine and the combination of neostigmine and glycopyrrolate both caused a similar expulsion of the stool, which was greater than with normal saline (median score 3 vs. 4 vs. 0, respectively)
2. Mean time to expulsion was 11.5 min (range 5-20 min) after neostigmine and 13.5 min (range 4-23 min) after the combination
3. There was no correlation between the level of SCI and likelihood of bowel evacuation with any of the infusates.

Cardenas et al. 2007; USA
PEDro = 6
RCT
N=78

Population: A total of 91 subjects with motor-incomplete SCI randomized to three groups:
(1) Fampridine, sustained release, 25 mg bid – Sex: 22 males, 8 females; Age: mean 44, range 23-66; Duration of injury: mean 8.3 years, range 1-30; Level of injury: 23 cervical, 7 thoracic; AIS grade: 14 C, 16 D
(2) 40 mg bid – Sex: 26 males, 4 females; Age: mean 42 years, range 21-67; Duration of injury: 10.8 years, range 1-35; Level of injury: 24 cervical, 6 thoracic; AIS grade: 12 C,  18 D
(3) Placebo – Sex: 24 males, 7 females; Age: mean 38, range 19-61; Duration of injury: mean 8.3 yrs, range 1-37; Level of injury: 26 cervical, 5 thoracic; AIS grade: 18 C, 13 D
Treatment: Drug treatment or placebo for 8 weeks
Outcome Measures: Number of days with bowel movement

1. A significantly larger number of subjects in the 25 mg bid (6/30 subjects) and 40 mg bid (7/30 subjects) groups had an increase in the number of days with bowel movements compared to subjects in the placebo group. Number of days increase not reported.

De Both et al. 1992; Netherlands
PEDro = 5
RCT
N=10

Population: 10 patients suffering from constipation due to complete supraconal spinal cord lesion; Age: mean 35.8, range 19-63; Level of injury: C6-L1; Time since injury: 1-12 months
Treatment: Cisapride 10 mg four times daily vs. placebo
Outcome Measures: Defecation frequency and ease, consistency of stools, percentage of defecations preceded by digital stimulation or suppository, time between suppository and successive defecation, oro-caecal and oro-anal transit time

1. No statistical difference between the number of defecations per week under the influence of cisapride and placebo
2. With respect to the ease of evacuation, a significant improvement in both the cisapride and placebo phase was observed
3. The mean degree of consistency of stools changed significantly with cisapride.
4. Percentage of defecations preceded by digital reflex stimulation or suppository use were unaffected by cisapride or placebo
5. There appeared to be a significant reduction of oro-caecal transit time with cisapride

Binnie et al. 1988; UK
Downs & Black =12
Pre-post
N=10

Population: mean age: 34.1yrs, 9 males, 1 female, age range 20-45yrs; level of injury: C4-T10, all subjects had complete injuries; length of injury: mean 8.1yrs, range 1-20 yrs
Treatment: Intravenous injection of 10 mg cisapride.  After an interval of at least 48 hours the subject was commenced on oral cisapride.
Outcome measures: Oro-caecal transit time

1. The colonic transit time (CTT) was reduced from 185 to 123 hours.

Longo et al. 1995; USA
Downs & Black = 9
Pre-post
N=15

Population: All male; 12 subjects with tetraplegia, 3 subjects with paraplegia, length of injury=3-356 months.
Treatment: After establishing baseline studies, patients with constipation received one oral cisapride 20mg tablet three times each day for one month. Subjects offered drug for two additional months, all measurements were repeated.
Outcome Measures: colonic transit study; anorectal manometry; bowel movement per day or week; intestinal transit and pelvic floor studies

1. All subjects had three months or more of treatment with cisapride.
2. 6/12 reported that symptoms of constipation improved.
3. 9/12 subjects reported that the amount of time needed to accomplish a bowel movement decreased.
4. No subject reported a worsening of constipation.

Segal et al. 1987; USA
Downs & Black = 9
Prospective Controlled Trial
N=20, Control N=8

Population: Age range was from 20 to 55 years, all subjects with complete SCI, 11 subjects with tetraplegia, 9 subjects with paraplegia, 8 controls
Treatment: subjects ingested a liquid meal, then within 2 weeks, ingested 2nd liquid meal while metoclopramide was administered intravenously; gastric emptying (GE) was evaluated after each liquid meal
Outcome Measures: half time of gastric emptying, gastric emptying patterns in the early  and later phases

1. The mean gastric emptying (GE) half time for a liquid meal decreased in the subjects with tetraplegia from 104.8 min to 18.8 min after treatment with metoclopramide.
2. The pretreatment mean GE of 111.5 min decreased to 29.1min among the subjects with paraplegia.