Table 1 Characteristics of included studies and quality assessment results

Bortolotti, M/2000

Italy

RCT

Patients affected by achalasia with an esophageal diameter of < = 5 cm

14

Mean age, 41 years; age range, 21–64 years

A 50-mg tablet of sildenafil

Placebo

Sildenafil inhibits the contractile

activity of the esophageal musculature of patients with

achalasia, decreasing lower esophageal sphincter tone

and residual pressure as well as contraction amplitude.

No side effects were observed, except for

headache in one case.

Bortolotti, M/2001

Italy

RCT

Healthy subjects

16

34 years, age range 22–56

 A 50-mg tablet of sildenafil

Placebo

Sildenafil

markedly inhibits the motor activity of the esophageal musculature by decreasing LES

pressure, wave amplitude, and propagation velocity

No side effects were observed, except for

headache in one case.

Rhee, P.L./2001

Korea

Before/ After

Healthy male adult volunteers

8

Mean age = 30.5 years

A 50-mg tablet of sildenafil

N.A

LES resting pressure significantly decreased after

sildenafil infusion. The body’s peristaltic amplitude gradually

decreased and eventually disappeared

No serious side effects were noticed

Bortolotti, M. /2002

Italy

RCT

Patients with symptomatic hypertensive LES

14

Mean age 35 years, range 28–55

 A 50-mg tablet of sildenafil

Placebo

Sildenafil inhibits the lower oesophageal sphincter tone and pressure wave

amplitude of patients with symptomatic hypertensive LES

No side effects were observed

Eherer, A. J./2002

Austria

Before/ After

Healthy subjects, nutcracker esophagus, hypertensive LES, and achalasia patients

Healthy subjects: 6,

Patients with esophageal disorder: 11

Normal subjects: aged 26–30 years,

Patients: aged 27–57 years

A 50-mg tablet of sildenafil

Placebo

Sildenafil lowers LOS pressure and propulsive forces in the body of the esophagus of

healthy subjects as well as in patients with nutcracker oesophagus, hypertensive LOS, and achalasia.

Two patients experienced side effects and did not want to continue treatment. (Side effects included: headaches, dizziness, fatigue, sleep disturbances, feeling of tightness in the chest at night.)

Mathis, C./2002

USA

Before/ After

Patients diagnosed with hypertensive

LES

N.A

N.A

Sildenafil (50 mg) dissolved

N.A

Sildenafil inhibits LES tone and the amplitude of contractions of the distal esophageal body in patients with hypertensive LES.

N.A

Lee, J. I. / 2003

Korea

Before/ After

Healthy subjects, patients with nutcracker esophagus

Healthy subjects: 8,

Patients with nutcracker esophagus: 9

Healthy subjects: 24.3 years,

Patients with nutcracker esophagus: 44.7 years

0.8 mg/kg sildenafil dissolved in 20 mL of water

distilled water

In both healthy subjects and patients with nutcracker esophagus, sildenafil decreased resting LOS pressure and

the amplitude of peristaltic pressure waves at 3, 8 and 13 cm above LOS. Sildenafil also prolonged the duration of LOS relaxation. It had no effect on the velocity of peristalsis or the amplitude of peristaltic

pressure waves 18 cm above LOS.

No noticeable side-effects reported

Kim, H. S. / 2006

Korea

Before/ After

Healthy subjects

8

Mean age : 38.5 years

50-mg dose of sildenafil

N.A

Sildenafil decreased the resting lower esophageal sphincter pressure

and prolonged the duration of lower esophageal sphincter relaxation

for the 45 min following its ingestion, and does not induce gastro-oesophageal reflux.

N.A

Lee, T. H./ 2012

Korea

RCT

Healthy volunteers

16

Mean age : 31.4 years

10 mg vardenafil

Water

Vardenafil decreased resting and residual LES

pressures, distal esophageal contraction, and bolus transit.

N.A

Rodriguez, R. / 2013

 N.A

Before/ After

Healthy volunteers, patients with type II/III achalasia, and hypertensive peristalsis

20

Healthy group: mean age 27.5

Patients: mean age 45 years

Single dose of 20 mg tadalafil

N.A

Tadalafil is a 5-PDE that induce a prolonged

and sustained effect on esophageal contractions, is well tolerated and it could be a promising

drug in the management of esophageal motor disorders.

Mild headache

Guevara-Morales /2014

N/A

Before/ After

Achalasic Patients

12

N/A

20 mgs tadalafil

N/A

Tadalafil may significantly reduced LES pressure and IRP in achalasia patients, and patients with Type 2 Achalasia had a better response.

Headache and back pain

Costa, T./2020

Brazil

Before/ After

Healthy volunteers

22

Mean age : 38.1 years

50 mg sildenafil

N.A

Sildenafil caused a significant reduction in distal contractile integral and integrated

relaxation pressure in the lower esophageal sphincter. In the proximal esophagus the alteration

in distal esophageal contraction caused a significant increase in contraction length, contractile

integral, and contraction duration; suggesting an adaptive compensation of the proximal esophagus

for the effect of sildenafil on distal esophageal motility.

There was no adverse event after administration of sildenafil.

Wong, M. W. /2020

Taiwan

RCT

Healthy subjects

15

Mean age: 27 years

50 mg sildenafil

Placebo

Sildenafil attenuates esophagogastric junction barrier function, resting LES pressure, and

LES relaxation. Both esophageal body contractility and contraction reserve are in-

hibited by sildenafil in healthy adults.

Significant adverse effects were not observed in patients.

Wong, M. W. /2021

Taiwan

RCT

Healthy subjects

17

Mean age : 30.2 years

50 mg sildenafil

Placebo

Sildenafil reduces both the success rate and the vigor of secondary peristalsis,

similar to that seen with primary peristalsis.

N.A