Table 1. Basis characteristics.

Author, year	Setting	Inclusion criteria	Exclusion criteria	Intervention	Number of patients (women)	Age: years (SD or Range)	Duration of disease: days (SD)
GI-symptoms
Achem, 1997 [25]	Randomized, double-blindtrial of 36 patients referredto the University ofFlorida/Jacksonville forevaluation of the maincomplaint of NCCP duringthe period of January 1992to September 1992, USA	Chest pain retrosternaland suggestive ofcoronary artery disease(squeezing or oppressiveand related to effortand/or emotion) with aduration of at least sixmonths prior to entry anda frequency of at leastthree episodes per week.Patients may have hadother esophagealsymptoms, such aspyrosis or dysphagia, butthe dominant complaint that brought the patient to medical attention was NCCP. GERD was documented by 24-hr ambulatory pH testing. All patients were deemed not to have cardiac disease by a cardiologist (coronary angiography or stress thallium test), all patients had a normal echocardiogram.	Other sources of chest pain: cardiac disease, epicardialcoronary artery disease and valvular heart disease,musculoskeletal causes ofchest pain, reproduction of chest pain on palpation of the chest wall or during arm/neck motion	Omeprazole 20 mgorally twice daily vs.placebo for 8 weeks	36 (23)	52 (N.R.)	<1
Bautista, 2004 [26]	Randomized, double-blind, placebo-controlled, crossover trial of 40 patients who were referred by a cardiologist after a comprehensive evaluation, with at least three episodes per week of unexplained chest pain as the predominant symptom, USA	At least three episodes per week of unexplained chest pain (angina like pain behind the breast bone) for a minimum of 3 months, normal or insignificant findings on coronary angiogram, or had insufficient evidence for ischemic heart disease using exercise treadmill, stress thallium, technetium 99 m tetrofosmin or technetium 99 m methoxy isobutyl isonitrile testing	Cardiac abnormality, severe liver, lung, renal, hematological or any other underlying disorder, previous empirical anti-reflux regimen, history of peptic ulcer disease or gastrointestinal surgery, unwilling or incapable of providing informed consent, and inability to fully complete all phases of the study, duodenal or gastric ulcer as well as other significant lesions on upper endoscopy	Lansoprazole 60 mg AM and 30 mg PM vs. placebo for 7 days	40 (9)	54 (3)	N.R.
Cossentin, 2012 [33]	Randomized, controlled, double-blinded trial with 43 GERD patients with abnormal 24-h pH tests seen in the Gastroenterology Service at the Walter Reed Army Medical Center, 2011, USA	18 years of age or older, have at least one symptom consistent with GERD (to include, but not limited to heartburn, acid taste in the mouth, regurgitation, burning epigastric pain and/or dyspepsia) and evidence of upright (percentage time >6.3) or supine (percentage time >1.2) reflux on 24-h pH testing	Prior gastric or esophageal surgery for the treatment of GERD, severe co-morbid illnesses, history of allergy to baclofen and pregnancy	Baclofen vs. placebo for 14 days	43 (16)	49 (14)	N.R.
Dickman, 2005 [27]	Randomized, double-blind, placebo-controlled, crossover trial of 35 patients with non-cardiac chest pain referred by a cardiologist after a comprehensive cardiac work-up, USA	At least three episodes per week of unexplained chest pain (angina alike pain behind the breast bone) for a minimum of 3 months, normal or insignificant findings on coronary angiogram, or had insufficient evidence for ischemic heart disease using exercise treadmill, stress thallium technetium 99 m tetrofosmin or technetium 99 m methoxy isobutyl isonitrile testing	Severe liver, lung, renal, hematological or any other severe co-morbidity, previous empirical anti-reflux regiment, history of peptic ulcer disease or gastrointestinal surgery, unwilling or incapable of providing informed consent, and inability to fully complete all phases of the study	Rabeprazole 20 mg AM before breakfast and 20 mg PM before dinner vs. placebo for 7 days	35 (12)	56 (10)	N.R.
Dore, 2007 [28]	Randomized controlled study of 266 consecutive patients with heartburn and/or regurgitation, dysphagia and/or odynophagia, with or without esophagitis attending the University Hospital of Sassari, Italy	Heartburn and/or regurgitation, dysphagia and/or odynophagia, with or without esophagitis	Previous endoscopy and or a defined diagnosis of ERD or NERD, upper gastrointestinal (GI) surgery and malignancy, anti-secretory drugs or PPIs during the 4 months before enrollment	Rabeprazole 20 mg vs pantoprazole 20 mg vs esomeprazole 20 mg vs lansoprazole 20 mg for 12 weeks	266 (190)	48 (18–82)	N.R.
Fass, 1998 [29]	Randomized, double-blind, placebo-controlled, crossover trial of 39 patients who were referred by a cardiologist after a comprehensive evaluation, with at least three episodes per week of unexplained chest pain as the predominant symptom, between January and December 1996, USA	At least three episodes per week of unexplained chest pain, insignificant disease or normal anatomy on cardiac angiogram, or lack of evidence of ischemic heart disease on exercise treadmill, stress thallium, technetium 99 m tetrofosmin or technetium 99 m methoxy isobutyl isonitrile testing	Medical contraindication for omeprazole therapy, had already been empirically treated with an anti-reflux regimen, reported a history of peptic ulcer disease or gastrointestinal surgery, or were unwilling or unable to provide informed consent, patients who were unable to fully complete all stages of the study	Omeprazole 40 mg AM and 20 mg PM vs. placebo for 7 days	39 (1)	60 (2)	N.R.
Jones, 2006 [34]	Randomized controlled, single blinded, trial of 28 patients attending the regional cardiothoracic center with angina-like chest pain in whom a coronary angiography was normal, UK	Angina like chest pain in whom coronary angiography was normal, to be able to attend the department over a period of at least 17 weeks, have no coexistent disease, and experience chest pain at least once a week	Esophageal reflux, proton pump inhibitor (it was necessary for them not to have responded to this medication)	4 week baseline period Hypnotherapy: by a therapist, initial tutorial (about condition and factors that may be involved), hypnosis induced by eye closure, followed by progressive muscular relaxation and standard deepening techniques vs. Supportive therapy plus placebo: by a research assistant, counseling and support, placebo medication total 12 sessions over a 17 week period	28 (18)	57	N.R.
Lind, 1997 [30]	Randomized, double-blind study of patients with heartburn, without endoscopic signs of esophagitis, treatment with omeprazole, 20 or 10 mg once daily, or placebo, for 4 weeks (n = 509) at 25 centers in Denmark and Sweden	Both sexes, 18 years or older, with a history of heartburn as the predominant symptom during the past 12 months, with episodes of heartburn occurring on at least 2 days weekly, and without any endoscopic signs of esophagitis	Presence or history of gastric or duodenal peptic ulcer disease or erosive/ulcerative esophagitis, presence of Barrett’s esophagus or an esophageal stricture, previous esophagogastric surgery, treatment with any investigational compound or with anti-secretory agents such as histamine H2-receptor antagonists or PPI in ulcer-healing doses within the month before endoscopy, concurrent cardiovascular, renal, or hepatic disease likely to complicate the evaluation of the study, suspected or confirmed malignancy, clinically significant abnormal findings in the pre-study laboratory screen, or pregnancy or lactation	Omeprazole 20 mg daily vs. 10 mg daily vs. placebo for 4 weeks	509 (303)	50 (N.R.)	N.R.
Pandak, 2002 [31]	Prospective, double-blind, placebo-controlled, parallel, crossover trial of 42 patients who presented with unexplained recurrent chest pain and subsequently had negative results on MIBI testing, ruling out a cardiac etiology, between May 1997 and August 1999, USA.	At least three episodes of chest pain per week of 6 months’ duration or longer	Gastric or duodenal ulcer, were already using anti-reflux medications, had omeprazole contraindications, had prior gastric surgery, or could not comply with the study protocol. Patients with physical exam or chest x-ray abnormalities that would explain their chest pain.	Omeprazole 40 mg orally twice daily vs. placebo for 2 weeks	42 (24)	45 (N.R.)	N.R.
Xia, 2003 [32]	Prospective, single-blind, placebo-controlled trial of 68 patients with chest pain for at least 12 weeks in the preceding 12 months, who were referred to the Cardiology Division of Queen Mary Hospital for evaluation by cardiac catheterization between November 1998 and February 2000, China	Patients who had a normal coronary angiograph, and whose chest pain was considered by a cardiologist to be non-cardiac in origin	Patients with apparent heartburn, acid reflux, dysphagia and dyspepsia	Lansoprazole 30 mg daily vs. placebo for 4 weeks	70 (42)	58 (10)	N.R.
musculoskeletal
Lehtola, 2010 [35]	Randomized, assessor-blinded, placebo-controlled trial of 114 female patients (referred by their GPs) aged 20–60 years with pain in the thoracic spine area during the period of September 1998 to May 2001, Finland	Female subjects, problems in the thoracic area, duration of the symptoms had to be less than 3 months prior to the study	The primary subjective problem was some pain other than thoracic pain (headache, neck pain etc.), a contra-indication to manipulation or acupuncture, and not having experienced pain in the thoracic area within the last 7 days	Facet-traction manipulation: as many segments between the area T3-T8 as necessary, lasted 10–15 min. vs. Acupuncture: points GB21, GV14, GV9–12, BL13–18 la, BL60 la, points GV9–12, lasted 30 min. vs. Placebo: interference-electrotherapy with suction cups without electricity, sucking between 0 and 0.2 bar, lasted 20 min	114 (114)	43 (N.R.)	N.R.
Stochkendahl, 2012 [36], [37]	A non-blinded, randomized controlled trial undertaken at an emergency cardiology department and 4 outpatient chiropractic clinics, 115 consecutive patients with acute chest pain of musculoskeletal origin, between August 2006 and March 2008, Denmark	Aged 18 to 75 years, have had a primary complaint of acute chest pain for less than 7 days duration, should be a resident of the local county, and should be able to read and understand Danish. Participants should have undergone diagnostic procedures to rule out ACS and should not have shown significant comorbidity or contraindications for spinal manipulative therapy.	Previous ACS, prior percutaneous coronary intervention or coronary artery bypass grafting, inflammatory joint disease, insulin-dependent diabetes, fibromyalgia, malignant disease, major osseous anomaly, osteoporosis, apoplexy or dementia, inability to cooperate, and pregnancy	Chiropractic: individual treatment strategy, 1 of 8 experienced chiropractors, high-velocity, low-amplitude manipulation directed toward the thoracic and/or cervical spine, a maximum of 10 treatment sessions of approximately 20 minutes’ duration each, 1 to 3 times per week for 4 weeks vs 15-minute consultation that chest pain generally had a benign, self-limiting course and, based on the clinical evaluation, gave individual instructions regarding posture and 2 to 3 home exercises aimed at increasing spinal movement or muscle stretch	115 (48)	51 (11)	N.R.
psychiatric drugs
Cannon, 1994 [49]	60 consecutive patients with chest pain underwent cardiac, esophageal, psychiatric, and pain-sensitivity testing and then participated in a randomized, double-blind, placebo controlled three week trial of clonidine, imipramine with a morning placebo, or placebo twice daily. This treatment phase was compared with an identical period of twice-daily placebo for all patients (placebo phase), USA	Normal coronary angiograms and no epicardial coronary-artery spasm after the intravenous administration of ergonovine (0.15 mg), normal left ventricular function at rest, no evidence of left ventricular hypertrophy or valvular heart disease (including mitral-valve prolapse) or echocardiography, blood pressure no higher than 160/100 mmHg when they were receiving no medication, and no musculoskeletal sensitivity that accounted for their characteristic chest pain	N.R.	Clonidine 0.05 mg at 9 AM and 9 PM for 1 week, then 0.1 mg for both doses thereafter vs. imipramine 25 mg at 9 PM for 1 week, then 50 mg nightly, always with a matching placebo at 9 AM vs. placebo at 9 AM and 9 PM	60 (40)	50 (29–72)	1590
Cox, 1998 [50]	Randomized, double-blind, cross-over trial of imipramine 50 mg daily vs placebo in 18 women with chest pain and normal coronary angiograms who were suffering at least two anginal episodes per week despite conventional anti-anginal medication, UK	Completely normal coronary angiogram; at least two episodes of anginal pain per week despite anti-anginal medication	Non-cardiac causes of chest pain and patients receiving anti-depressant therapy for previously diagnosed psychiatric disorders	Imipramine 50 mg daily vs. placebo for 5 weeks	18 (18)	53 (35–72)	1500
Doraiswamy, 2006 [51]	Single-site, double-blind, placebo-controlled study of the efficacy and safety of paroxetine in the treatment of chest pain in 50 patients with normal coronary angiograms or stress tests, USA	Males and females between the ages of 18 and 85 experiencing chest pain at minimum 1 to 2 times per week and with a documented normal coronary angiogram or stress test	Treatment with another antidepressant within the 2 weeks (5 weeks for fluoxetine) of beginning double-blind therapy. Medications: narcotics, reserpine, methyldopa, guanethidine, clonidine, local or general anesthetics, and any other psychotropic medication with the exception of hypnotics or benzodiazepines on a minimal, case-by-case basis	Paroxetine 10 mg for 1 week, then increased to 20 mg daily or adjusted to a maximum of 50 mg daily based on clinical response vs. placebo for 8 weeks	50 (21)	53 (N.R.)	1158
Keefe, 2011 [52]	Randomized clinical trial examined the separate and combined effects of CST and antidepressant medication (sertraline) in participants with non-cardiac chest pain. 115 patients diagnosed with NCCP were randomly assigned to one of four treatments: CST plus sertraline, CST plus placebo, sertraline alone, or placebo alone. Participants were recruited from Duke University Medical Center, satellite clinics, and the community from February 2002 to October 2005, USA	Complaints of chest pain in the previous 6 months, received a negative stress test within the past 2 years, normal coronary angiogram within the past 2 years, or had a survival probability >98% at 2 years, a low likelihood of significant coronary artery disease (<25%) on the National Cholesterol Education Program’s (NCEP) modification of the Framingham Risk Calculator (FRC), able to swallow oral medication, and age 18–85 years	Other cardiac problems associated with chest pain, current use of antidepressant medications or medications significantly affecting pain, a history of drug or alcohol abuse within the past 6 months, pregnancy, severe psychopathology (i.e., suicidal patients, severe depression, or psychosis), or treatment with another antidepressant within a period of less than five times the half-life of the drug concerned (e.g. fluoxetine within 5 weeks of beginning double-blind therapy)	Sertraline alone: started at 50 mg daily, adjusted to a maximum of 200 mg within the initial 10 weeks, then dose level stabilized for the remaining 24 weeks vs. CST: 6 sessions, lasted 60 min., bi-weekly for 10 weeks, then 6 follow-up sessions monthly for 6 months with placebo vs. CST with sertraline vs. placebo alone	115 (77)	48 (12)	N.R.
Rao, 2007 [53]	Randomized, controlled, double-blind study with 24 patients with unexplained noncardiac chest pain who were referred to a tertiary care center, USA	At least 12 weeks, which need not be consecutive, in the preceding 12 months of: (a) midline chest pain or discomfort that is not of burning quality and (b) absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with a recognized pathologic basis. Also, they were required to have a negative cardiac stress test (treadmill exercise stress test, stress thallium test, or stress technetium 99 m-methoxy isobutyl isonitrile [MIBI]) or negative coronary angiography, normal chest X-ray, normal upper GI endoscopy, normal esophageal manometry, and either a normal 24-h pH study (% fraction time of pH <4.0 was <5) or no improvement in chest pain after 2 months of b.i.d. proton pump inhibitor (PPI) therapy	Referred by cardiologists or after a cardiac source for chest pain, muscular-skeletal sources of chest pain, patients who were hospitalized, or those who had significant comorbid illnesses such as cardiac, pulmonary, renal, or hepatic disease or those with diabetes, neuropathy, history of peptic ulcer disease, seizures, or bronchial asthma and those with known allergy or adverse reaction to theophylline, history of psychiatric disorders or who were under treatment with psychotropic drugs	Theophylline oral capsules of 200 mg daily vs. placebo for 4 weeks after meals (crossover: 1 week washout period, then alternate treatment)	24 (16)	44 (22–70)	>84
Varia, 2000 [54]	Single-site, double-blind, placebo-controlled study of the efficacy, tolerability, and safety of sertraline in the treatment of chest pain in 30 outpatients who otherwise had normal coronary angiograms or stress tests, USA	Men and women 18 to 85 years of age who were able to swallow oral medication and who had noncardiac chest pain, negative stress test or normal coronary angiogram. Patients who agreed to abstain from alcohol and to adhere to protocol requirements.	DSM-IV criteria for major depression, panic disorder, or drug or alcohol abuse or dependence. Patients with any active or clinically significant condition, including sensitivity to sertraline, which could possibly affect absorption, distribution, or metabolism of the study drug, Treatment with a depot neuroleptic drug, another antidepressant, fluoxetine, monoamine oxidase inhibitors, reserpine, methyldopa, guanethidine, or clonidine, local or general anesthetic agents, drugs known to interact with sertraline, antidepressants, other psychotropic medications, or medications significantly affecting pain	Sertraline started at 50 mg daily, adjusted to a maximum of 200 mg vs. placebo for 8 weeks	30 (N.R.)	N.R.	N.R.
Wulsin, 2002 [55]	Randomized, controlled, non-blind, trial of a protocol intervention to initiate panic disorder treatment of 156 enrolled participants, all at low to moderate risk for acute coronary syndrome, admitted to the University Hospital Chest Pain Center in the ED during a 14- month period (March 1998 to May 1999), USA	All adult (≥18 years)	Cognitive impairment, active severe substance abuse, and bipolar disorder	Intervention: patient education by the research assistant about panic disorder according to study protocol, initiation of treatment with a 1-month supply of paroxetine 20 mg/d vs. Usual care: consisted of reassurance that the patient has no cardiac disease, care as needed through primary care physician, telephone follow-up at 3 months	50 (35)	43 (N.R.)	N.R.
psychological interventions
Arnold, 2009 [38]	Single center, non-blinded, randomized controlled trial of 700 consecutive patients with acute chest pain and no clear diagnosis at initial presentation referred to the chest pain unit of an emergency department between May 2006 and September 2007, UK	Chest pain of possible cardiac origin, were aged over 25, had no changes for acute coronary syndrome on a diagnostic electrocardiogram	Suspected life threatening non-cardiac disease, known coronary heart disease presenting with recurrent or prolonged episodes of cardiac-type chest pain	Standard verbal advice or verbal advice followed by an information sheet	700 (269)	49 (12)	N.R.
Esler, 2003 [39]	Randomized controlled, non-blinded, trial with 59 patients who presented to a large, university-affiliated Level One Trauma Center ED with chief complaints of chest pain and were determined to have NCCR, USA	No known history or suspected history of coronary artery disease, other significant medical illness (e.g. congestive heart failure, pulmonary embolism, or lung disease), and no obvious proximal cause of their chest pain (e.g. pneumonia, bronchitis, or chest trauma)	Current psychosis, suicidal or homicidal ideation, and those who were intoxicated from alcohol or other drugs at the time of admission to the ED	CBT (cognitive behavioral treatment) intervention (involving psycho education, diaphragmatic breathing exercises, and cognitive restructuring about physical symptoms), 60 min, 1 psychologist vs. treatment-as-usual	59 (27)	41 (12)	<30: 45.8%, 30–180: 15.3%, 180–720: 5.1%, >720: 33.9%
Gasiorowska, 2008 [56]	A randomized, controlled pilot study of 39 patients with at least three episodes per week of unexplained chest pain for 3 consecutive months, Gastroenterology Service, University of Arizona Health Sciences Center, USA	at least three episodes per week of unexplained chest pain for 3 consecutive months, either insignificant coronary artery disease, normal coronary arteries on cardiac angiogram or lack of evidence of ischaemic heart disease on an exercise treadmill, stress thallium, technetium 99 m tetrofosmin or technetium 99 m sestamibi testing, normal upper endoscopy, pH testing and esophageal manometry	severe underlying comorbidities, upper airway symptoms such as hoarseness, wheezing and laryngospasm, diabetes mellitus, scleroderma, gastroparesis, peptic ulcer disease, history of gastrointestinal surgery, depression, autonomic or peripheral neuropathy or neuromuscular disorder, patients using narcotics, benzodiazepines, tricyclic antidepressants or selective serotonin reuptake inhibitors, patients unable to complete the upper endoscopy, 24-hour esophageal pH monitoring or esophageal manometry, patients demonstrating erosive esophagitis, Barrett’s esophagus or other GERD-related complications during upper endoscopy, abnormal pH test or manometry results	Johrei treatment (process of transmission of healing energy) delivered by an experienced and certified Johrei practitioner in a hospital clinic with minimal interaction with the patient. Each Johrei treatment session usually lasts 20 min. vs. waiting list	39 (13)	54.5 (11.9)	N.R.
Hess, 2012 [40]	Randomized controlled, single blinded, trial of 204 patients attending the ED of Saint Mary’sHospital at the Mayo Clinic with symptoms suggestive of ACS, USA	Aged >17 years who presented to the ED with primary symptoms of non-traumatic chest pain and who were being considered for admission to the ED observation unit for monitoring and cardiac stress testing within 24 hours	Elevated initial cardiac troponin T levels above the 99th percentile reference limit (99th percentile, <0.01 ng/mL; lower limit of detection, 0.01 ng/mL; 10% coefficient of variation, 0.035 ng/mL), known coronary artery disease (defined as 1 50% stenosis on cardiac catheterization; prior electrocardiographic changes indicative of ischemia, e.g. ST-segment depression, T-wave inversion, or left bundle branch block, perfusion defects or wall motion abnormalities on previous exercise, pharmacological, or rest imaging studies; previous documentation of acute myocardial infarction, or if no records were available, patient self-report of coronary artery disease), cocaine use within the previous 72 hours by clinician history, or pregnancy	Decision aid (information paper): included a 100-person pictograph depicting the pretest probability of acute coronary syndrome and available management options (observation unit admission and stress testing or 24–72 hours outpatient follow-up) after initial evaluation (ECG, interpretation, results of initial cardiac troponin testing, plan for serial cardiac markers) vs. usual care	204 (120)	54.7 (11.9)	0.5 (2)
Jonsbu, 2011 [41]	A randomized controlled, non-blinded, trial of 40 patients with persistent complaints six months after a negative evaluation at a cardiological outpatient clinic between May 2006 and May 2007 at Molde Hospital, Norway	Aged between 18 and 65 years, persistent symptoms or limitations in activity six months after the cardiac evaluation: at least weekly symptoms of chest pain or palpitations, at least “some impact” on family life, social life, or work from the symptoms, at least “rare but sometimes” avoidance of physical activity because of worry about the heart	Cardiac disease in need of treatment	Intervention: cognitive behavioral treatment (CBT), 3 sessions, lasted 60–90 min., at the Psychiatric Outpatient Clinic at Molde Hospital vs. Control group: usual care from their general practitioner, free to use the health care system when needed	40 (26)	52 (22–65)	360
Lahmann, 2008 [42]	A randomized, controlled, clinical investigation of 22 patients presenting with non-specific chest pain at the University Hospital of Regensburg, Germany	Over the age of 18 years who presented with NSCP	Any underlying somatic disorders; any severe and disabling psychiatric disorder, such as schizophrenia or dementia; as well as patients undergoing psychotherapy and those current enrolled for retirement payment	Functional relaxation: started with a 60-minute psychosomatic-education session, then 10 group-therapy sessions (each 90 min) during 6 weeks vs. enhanced medical care: treatment-as-usual plus 2 case-management counseling interviews (personal-care skills, shared decision-making)	22 (12)	44.35	1773 (2218.5)
Mayou, 1997 [44]	Randomized controlled, non-blinded, trial of 37 patients presenting with chest pain and reassured by a cardiologist they do not have heart disease, UK	Aged 18–65, presence of persisting non-cardiac chest pain occurring at least once a week in the month before the assessment	Cardiac diagnosis, current major depression, living outside the country and being unable to speak English	Cognitive behavioral treatment: consisted of up to 12 sessions of individual therapy with a research counseling psychologist (D.S.) trained and supervised by a clinical psychologist (I.K.) vs. usual care	37 (22)	49 (N.R.)	<180: 11, 180–720: 12, >720: 11
Mayou, 2002 [43]	A randomized controlled, single-blind, trial within a cardiology clinic (referred from primary care practice) at a district general hospital, 80 consecutive patients diagnosed as having benign palpitation ± either palpitation due to awareness of extrasystoles or sinus rhythm ± with associated distress or disability, UK	Aged 17 or over referred to a district cardiac clinic for the assessment of palpitation, suffering from benign palpitation and who described distress or disability	Subjects with very short histories or who did not describe distress or disability	Intervention group: usual care plus nurse-delivered intervention based on cognitive-behavioral principles coordinated with cardiological care, derived from experience with the early treatment of NCCP vs. Control group: usual cardiological care, with no contact with a cardiac nurse either in out-patients or by telephone	80 (57)	44 (N.R.)	N.R.
Potts, 1999 [45]	Randomized, non-blinded, trial of 60 patients who had continuing chest pain despite cardiological reassurance following haemodynamically normal angiography in the Departments of Cardiology of the Royal Infirmary and Western General Hospitals in Edinburgh, Scotland	Aged 18–70, recent (within the last year) coronary angiography for the investigation of chest pain revealed coronary arteries which were either normal or <50% stenosed, chest pain continuing at least twice weekly after angiography, despite reassurance by the cardiology team, and residence within easy travelling distance of Edinburgh	Past history of myocardial infarction, or serious concurrent physical or psychiatric illness	Intervention (CBT): small groups with a maximum of six subjects. Groups met weekly for 4 weeks, then every two weeks for a further 4 weeks. Each session lasted 2 h	60 (36)	54 (N.R.)
Sanders, 1997 [46]	Randomized controlled, single-blind, study of 57 consecutive patients with chest pain and normal angiograms over a 12-month period, UK	Normal coronary arteries, not need further medical investigations	All those who were either admitted to a Day Case Unit, and went home once they had received the results of the angiogram, or else stayed overnight on the cardiac ward	1-hour intervention: individualized information and discussion session by a specially trained cardiac nurse, together with a handout and cassette providing information and advice and telephone follow-up to discuss progress, answer questions and reiterate advice vs. usual care	57 (36)	N.R.	<180: 16, <720: 21, >720: 19
Van Peski, 1999 [48]	Randomized controlled, non-blinded, trial of 72 patients presenting with chest pain referred by their general practitioners to the cardiology clinic of the Leiden University Hospital or the Diaconessenhuis Hospital between 1992 and the first months of 1996 and who had received a discharge diagnosis of NCCP, Netherlands	18 to 75 years old with chest pain as the main complaint, who had a normal cardiovascular system according to a cardiologist	Proven coronary artery disease or myocardial ischemia, as demonstrated by coronary angiography, exercise testing, laboratory examination, electrocardiogram, or chest x-ray, a history of typical angina pectoris; insufficient fluency in Dutch, current psychiatric treatment for NCCP, current diagnosis of an organic mental syndrome, psychotic disorder; major depression, bipolar disorder, or use of psychoactive substances (excluding nicotine) within 3 months before study entry	Cognitive behavioral treatment: 4 to 12 weekly sessions of 45 to 60 minutes, depending on the severity of the patient’s problem, the maximum duration of therapy was 6 months. Treatment was modeled after cognitive-behavioral therapy for panic, hypochondriasis, and unexplained physical symptoms, each patient received written information about the therapy model and treatment procedures. The therapists were a physician with basic training in cognitive-behavioral therapy and a senior psychologist trained in cognitive-behavioral therapy vs. Usual care: free to use health resources as they saw fit. They were seen in the cardiology clinic for the follow-up assessments 6 months and 12 months after the baseline interview	72 (36)	49 (11)	1500 (1770)

ACS, acute coronary syndrome; CBT, cognitive behavioral therapy; CST, coping skills training; ECG, electrocardiogram; GERD, gastroesophageal reflux disease; GI, gastro-intestinal; mg, milligram; MIBI, methoxy-isobutyl-isonitril; min, minutes; n.r., not reported; NCCP, non-cardiac chest pain; NSAID, nonsteroidal antiinflammatory drugs; PPI, proton-pump inhibitor; vs., versus.