Inclusion Criteria:
Patients can participate in this study if:
1. A minimum of 18 years old;
2. Ineffective Esophageal Motility (IEM) or absent contractility, as determined on HRM in the last three months before inclusion in the study, using the Chicago classification v4.0 (1).
IEM is defined as \>70% ineffective or ≥50% failed swallows with a normal integrated relaxation pressure (IRP4). IEM includes a weak contraction (DCI ≥ 100 mmHg·s·cm and \<450 mmHg·s·cm), failed peristalsis (DCI \< 100 mmHg·s·cm), or fragmented peristalsis (a large break (\>5 cm length) in the 20-mmHg isobaric contour with DCI \> 450 mmHg·s·cm).
Absent contractility is defined as 100% failed swallows (DCI \< 100 mmHg·s·cm), with a normal IRP4.
3. Have completed a gastro-duodenoscopy, within 12 months, showing no anatomical abnormality of the stomach or esophagus, which can explain the patients' symptoms.
4. History of dysphagia for at least 2 months, at least twice per week in the last month.
5. Sexually active women of childbearing potential participating in the study must be using an appropriate form of contraception. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used barrier contraception. If the female patient has not been on oral, injectable, implantable or intrauterine contraception, a urinary pregnancy test will be performed prior to administration of Buspirone/Placebo.
6. Subjects must be capable of understanding and be willing to provide signed and dated written voluntary informed consent before any protocol-specific screening procedures are performed.
Exclusion Criteria:
Patients cannot participate in this study if:
1. Endoscopic signs of severe erosive esophagitis (grade C or D, Los Angeles classification) on endoscopy performed off PPI treatment in the 12 months prior to screening, or ≥ grade B when endoscopy is performed during PPI treatment.
2. Systemic diseases, known to affect esophageal motility (i.e. systemic sclerosis)
3. Surgery in the thorax or in the upper part of the abdomen (appendectomy and cholecystectomy are allowed).
4. Hiatal hernia ≥3 cm
5. QT c\>450 ms.
6. Use of medication that effect cholinergic function such as anticholinergics, tricyclic antidepressants.
7. Concomitant promotility agents such as prucalopride or domperidone.
8. Concomitant use of more than one benzodiazepine.
9. Significant neurological, respiratory, hepatic, renal, hematological, cardiovascular, metabolic or gastrointestinal cerebrovascular disease as judged by the investigator.
10. Major psychiatric disorder.
11. Pregnancy or breastfeeding.
12. History of poor compliance.
13. History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.
14. History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements.
