Achalasia is a primary esophageal dysmotility disorder. Despite the high volume of studies addressing the conventional treatments for achalasia, few are debated regarding the non-conventional treatments, such as cardiectomy, cardioplasty, endoluminal substances injection (ethanolamine oleate, polidocanol, botulinum toxin), stents, and certain drugs (beta-agonists, anticholinergic, nitrates, calcium channel blockers, and phosphodiesterase inhibitors).

A critical review was performed.

Endoscopic, surgical, and pharmacological treatments were included. A qualitative synthesis was presented.

Non-conventional therapeutic options for treating achalasia encompass medical, endoscopic, and surgical procedures. Clinicians and patients need to know all the tools for the management of achalasia. However, several currently available studies of non-conventional treatments lack high-quality evidence, and future randomized trials are still needed.

This article reviews currently available pharmacological options available for the treatment of achalasia, with a special focus on the role of botulinum toxin (BT) injection due to its superior therapeutic effect and side effect profile. The discussion on BT includes the role of different BT serotypes, better pharmacological formulations, improved BT injection techniques, the use of sprouting inhibitors, designer recombinant BT formulations and alternative substances used in endoscopic injections. The large body of ongoing research into achalasia and BT may provide a stronger role for BT injection as a form of minimally invasive, cost effective and efficacious form of therapy for patients with achalasia. The article also explores current issues and future research avenues that may prove beneficial in improving the efficacy of pharmacological treatment approaches in patients with achalasia.

Idiopathic achalasia (IA) is a primary motor disorder of the esophagus. Recently, ethanolamine oleate (EO) has been introduced as a novel therapy in IA. We investigate the long-term efficacy of EO injection in the selected IA patients. Two hundred twenty patients with IA were evaluated prospectively. Thirty-one patients who were resistant to or poor candidate of pneumatic balloon dilation and/or cardiomyotomy were enrolled in this study. EO was injected into the lower esophageal sphincter three times at 2-week intervals. Patients were evaluated with the achalasia symptom score (ASS), timed barium esophagogram, and manometry before and after the injections. A good response was defined as a greater than 50% reduction from baseline in the ASS, height and/or volume of barium in TBE, and absence of severe dysphagia or regurgitation at 1.5 months after the last injection. Relapse was defined as two or more points increase in dysphagia score after an initial good response. The mean age of patients was 49.32 ± 19.3 years. Twenty-nine patients had a good response and two had a poor response. The mean ASS decreased from 12.48 (±2.06) to 4.50 (±2.96) (P = 0.0001), and the mean volume of barium decreased from 115.35 (±93.40) to 45.50 (±60.86) mL at 1.5 months after the last injection (P = 0.0001).The mean lower esophageal sphincter pressure was 30.47 ± 13.95 before the treatment and decreased to 14.30 ± 11.89 at 1.5 months after the treatment. (P = 0.0001). The mean duration of follow up was 30.16 ± 11.3 (18-68) months. Twelve patients in whom symptoms relapsed were treated effectively with reinjection. In some patients, minor complications (chest pain and erosion in the distal esophagus) occurred. This study indicates that EO has a long-term effect and can be considered for use in the selected IA patients.

Endoscopic sclerotherapy (EST) with ethanolamine oleate (EO) was proposed as a treatment for achalasia, based on the well-known necrotizing effect against the esophageal muscle layers. The aim of this study is to evaluate long-term efficacy of EST.

Four consecutive series of patients with achalasia were treated according to different schedules over a period of 20 years, by using EO or polidocanol (PD). The primary outcome was dysphagia relief. Secondary outcomes were lower esophageal sphincter pressure, esophagogram, gastroesophageal reflux and endoscopic ultrasonography (EUS). Patients not responding to EST were treated with 30 mm dilation.

A total of 103 patients completed the treatment. On medium-term evaluation, 75 patients who completed the treatment reached a clinical response labeled as "good," 23 were assessed as "fair," and 5 were assessed as failures. EUS has become a very informative tool to guide the treatment. The overall follow-up lasted for 87.9 ± 66.7 months. Twelve patients experienced a late failure. The cumulative expectancy of being free of recurrence was 90 % at 50 months with EO, but it was only 65 % with PD. Those patients who responded to rescue measures remained in good or fair clinical condition during the remaining follow-up. Young age, PD, and the so-called fusiform pattern on esophagogram proved to be significant predictors of poor prognosis.

EST with EO is a promising alternative to classic therapies for achalasia. In contrast, PD-treated patients showed an important trend to fibrosis and clinical recurrence. Dilation seems particularly effective after EST, when this technique has failed.

Idiopathic achalasia (IA) is a chronic disease without definite therapy. Ethanolamine oleate (EO) has multiple biological effects, including inflammatory activities. We investigated the efficacy of EO injection in selected patients with IA.

One hundred and thirty-six patients with IA were evaluated prospectively. We evaluated the efficacy of EO injection in 13 patients with IA that are resistant to or a poor candidate of pneumatic balloon dilation and/or cardiomyotomy at the Digestive Disease Research Center, Shariati Hospital, Tehran, as the major referral center for achalasia in Iran in an interventional study. Diluted EO was injected in a divided dose into each of four quadrants of lower esophageal sphincter, using a standard sclerotherapy needle. Injection was repeated at 2 and 4 weeks after first injection. The patients were evaluated with achalasia symptom score (ASS) and timed barium esophagogram (TBE) before and after injections. Good response was defined as a decrease in ASS of at least 50% of baseline and decrease in height and volume of barium of at least 50% of baseline in TBE, at 1.5 months after the last injection. Side-effects were recorded.

All patients (13 cases) had good ASS (decreased, ≥ 50%) and good TBE (decreased in height and volume of barium, ≥ 50%) response rate. The mean ASS decreased from 11.38 (± 1.5) to 3.23 (± 1.96) at 1.5 months after the last injection (P=0.001). The mean volume of barium in TBE decreased from 81.38 ml (± 51.11) to 40.69 ml (± 61.22) at 1.5 months after the last injection (P=0.016). The mean duration of follow-up was 17.83 (± 1.12) months. Symptoms of six patients relapsed; all of them were treated effectively with reinjection.

This study indicates that EO is well tolerated and potentially effective in patients with IA that might be explained by the local inflammatory properties of EO. As presented data are too preliminary to support the routine use of EO in the treatment of all patients with IA; its use in selected cases can be considered.

Achalasia is an uncommon primary oesophageal motor disorder with an unknown aetiology. Therapeutic options for achalasia are aimed at decreasing the lower oesophageal sphincter pressure, improving the oesophageal empting, and most importantly, relieving the symptoms of achalasia. Modalities for treatment include pharmacologic, endoscopic, pneumatic dilatation and surgical. The decision of which modality to use involves the consideration of multiple clinical and economic factors.

To review the management strategies currently available for achalasia.

A Medline search identified the original articles and reviews the published in the English language literature between 1966 and 2006.

The results reveal that pharmacotherapy, injection of botulinum toxin, pneumatic dilatation and minimally invasive surgical oesophagomyotomy are variably effective at controlling the symptoms of achalasia but that each modality has specific strengths and weaknesses which make them each suitable in certain populations. Overall, pharmacologic therapy results in the shortest lived, least durable response followed by botulinum toxin injection, pneumatic dilatation and surgery, respectively.

The optimal treatment for achalasia remains an area of controversy given our lack of complete understanding about the pathophysiology of the disease as well as the high numbers of clinical relapse after treatment. Further research focusing on optimal dosing of botulinum toxin injection and optimal timing of repeated graduated pneumatic dilatations could add to our knowledge regarding long-term therapy.

Swallowing is a complex mechanism based on the coordinated collaboration of tongue, pharynx and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain or regurgitation. The major primary esophageal motility disorders--achalasia, diffuse esophageal spasm, hypercontractile esophagus ('nutcracker esophagus') and non-specific motility disorder--are of unknown etiology. Other esophageal diseases, such as cervical diverticula or gastroesophageal reflux disease, might also be caused by a primary esophageal motility disorder. Medical treatment of esophageal disorders with esophageal hyper- or dysmotility requires agents that reduce esophageal contractile force (anticholinergic agents, nitrates, calcium antagonists). Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment of esophageal motility disorders is rather disappointing. Calcium channel antagonist, alone or in combination with anticholinergics or nitrates, can be used as a medical trial, especially in mild achalasia. However, medical therapy is clearly inferior to pneumatic balloon dilation therapy. Recently, botulinum toxin injection was suggested as a therapeutic option in achalasia patients with good results on lower esophageal sphincter pressure (LESP) and symptom scores that were similar to the results achieved by pneumatic balloon dilation. Hypercontractile esophagus shows a good manometric response to calcium channel antagonists, but only little clinical effect in terms of improvement of symptoms. Diffuse esophageal spasm is a relatively rare disease and few clinical studies are available. The use of calcium channel antagonists can be beneficial, at least in some patients with diffuse esophageal spasm. From clinical and epidemiological studies, there is some evidence of a 'psychological' component in the pathogenesis or perception of esophageal symptoms. There is some clinical benefit from centrally acting drugs such as benzodiazepines or antidepressants. With the exception of botulinum toxin for achalasia, medical therapy of primary esophageal motility disorders is rather limited and the clinical results are poor. Further understanding of esophageal pathophysiology as well as development of new receptor-selective drugs might increase our chances of a successful treatment of primary esophageal motility disorders.

This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Practice Economics Committee. The paper was approved by the committee on September 27, 1998.