Research Review by Dr. Steve Burnie©

Date:

Feb. 2008

Study Title:

Clinical trial: acupuncture vs. doubling the proton pump inhibitor dose in refractory heartburn

Authors:

Dickman R et al.
Authors’ Affiliations: Clinical Research Group, Section of Gastroenterology, Southern Arizona VA Health Care System and University of Arizona, USA

Publication Information:

Alimentary Pharmacology & Therapeutics 2007;26:1333-44.

Summary:

Gastro-esophageal reflux disease (GERD) is a common chronic medical problem, with 44% of American adults reporting GERD-related symptoms (heartburn and/or regurgitation) at least once per month, and 20% once per week. The best relief from GERD symptoms to date has been found with the daily use of proton pump inhibitors (PPIs). These drugs have become the primary treatment choice for GERD in general medical practice, however recent studies have shown continued symptoms in 25-42% of patients treated with standard-dose PPIs, making PPI failure one of the most common reasons for GERD-related visits to gastroenterologists.

The current standard of care when PPI fails to control GERD is doubling the drug dose even though only 20-25% of PPI-failure patients show significant improvements in symptoms using this strategy. Patients who continue to suffer from daily GERD symptoms are six times more likely to use complementary and alternative approaches such as acupuncture, aromatherapy, chiropractic, homeopathy and reflexology to address their disorder than those without acid reflux.

Significant improvements in gastrointestinal (GI) motility, acid secretion, neurohormonal levels and sensory thresholds for pain have been demonstrated using acupuncture for various GI disorders. The purpose of this study was to test the effects of adding acupuncture vs. doubling the PPI dose in patients with GERD who failed to respond to once-daily PPI.

Thirty adult patients were enrolled in this study with GERD symptoms of at least 2 days per week while taking standard-dose PPI (20 mg omeprazole once per day) over a minimum of 3 months. Patients were randomized into one of two groups matched for age, sex, and body mass index. All patients received an upper endoscopy to assess mucosal abnormalities in the esophagus, stomach, and first portion of the duodenum.

The trial ran for 5 weeks, with a 1-week baseline symptom assessment period to ensure subjects met inclusion criteria, followed by treatment in one of the two groups: 40mg omeprazole, or 20mg omeprazole and acupuncture. A sham acupuncture arm was not added to this study because of the authors’ observation that numerous studies show superficial, sham and placebo acupuncture also provide an active therapeutic effect, particularly in pain conditions.

They conclude, therefore, that a true sham or placebo acupuncture method does not currently exist. Acupuncture was provided using Traditional Chinese Medicine (TCM) acupoints established by a literature search and consensus among three experienced traditional acupuncturists. Five acupoints were selected to “calm” and “regulate” the stomach from a TCM perspective, perhaps translating into regulation of acid secretion and gastric motility from a biomedical perspective. The chosen points were:
  1. Pericardium 6 (P6) – located 2 cun (a unit of relative distance; one cun is the width of the patient’s thumb) proximal to the wrist crease between the palmaris longus and flexor carpi radialis tendons
  2. Stomach 36 (ST 36) – located one cun lateral to the tibial tubercle
  3. Liver 3 (Liv 3) – between the 1st and 2nd metatarsal bones on the dorsum of the foot
  4. Conception Vessel 12 (CV 12) – midway between the umbilicus and xiphoid process
  5. Conception Vessel 17 (CV 17) – on the sternum at the level of the 4th intercostal space
If a diagnosis of “dampness” was made by the acupuncturist, including a history of loose stools or diarrhea and sensation of epigastric heaviness, an additional point was added:
  1. Spleen 9 – in the depression posterior and inferior to the medial condyle of the tibia
Acupuncture was provided for 25 minutes per session three times per week for the first 2 weeks and twice per week for the last 2 weeks, for a total of 10 treatments. Minimal practitioner-patient interaction was given to isolate the effect of the acupuncture by having the acupuncturist out of the treatment room except for insertion and manual needle stimulation once every 5 minutes. All needles except CV17 and CV 12 were inserted bilaterally and left in the patient for 20 minutes.

Results of this study:
  • all 30 patients completed this 5 week study; 15 receiving daily double-dose PPI and 15 receiving daily standard-dose PPI and 10 acupuncture treatments
  • no significant side effects were reported (one patient in the acupuncture group reported mild wrist pain that resolved within 2 weeks with no additional interventions)
  • baseline measurements were similar between the groups for all measures
  • at completion of the 4 week intervention, patients in the acupuncture group demonstrated significant decreases in mean night-time heartburn, daytime heartburn, acid regurgitation, dysphagia and chest pain scores
  • in comparison, the double-dose PPI group showed no significant improvements in the mean score of any measure from baseline

Conclusions & Practical Application:

Proton pump inhibitor failure is an important dilemma facing GERD patients and their physicians. Although doubling the dose of PPI is a standard approach to help patients who continue to have GERD with the regular dose, it is associated with improvements in only a modest number of patients. It is clear that different approaches are necessary to aid patients who remain symptomatic while on PPIs.

This study is the first to demonstrate that acupuncture is more efficacious than adding a second dose of PPI for patients who have failed to control symptoms with once daily PPI. Acupuncture provided significant improvements in night-time heartburn, daytime heartburn and acid regurgitation after only 10 sessions of treatment, while doubling the PPI dose yielded no benefits. This study included a small number of subjects in each arm, however the combined effect of a very limited consequence of doubling PPI dose and the profound therapeutic benefit of acupuncture allowed for a clear demonstration of superiority of acupuncture plus PPI. It should be noted that this study only examined short-term benefits (up to 4 weeks) and long-term evaluation of this treatment adjunct is needed.

Acupuncture alone was not compared to double PPI dose, as all of the patients demonstrated at least some response to the regular dose of PPI. Adding acupuncture to regular PPI use is closer to the clinical scenario that many physicians face where other drugs are commonly added to PPI when the regular dose fails.

Although numerous studies have shown that acupuncture may suppress gastric acid secretion in both animals and humans, the mechanism by which it improves GERD symptoms remains to be elucidated. It is unlikely that suppression of gastric acid secretion is the main mechanism of benefit of acupuncture for patients who have not improved while on PPIs, as the majority (60-70%) of these patients have normal esophageal acid exposure during pH testing. This may also explain the limited benefit of increasing PPI dose in patients who have failed to receive benefits from single dose PPI.

Several other mechanisms have been proposed that would explain the benefits of acupuncture for people with GERD. Acupuncture enhances gastric peristalsis and accelerates gastric emptying in dyspeptic patients observed by ultrasonography. Although delayed gastric emptying has been shown to contribute to failure of PPI once daily, the authors do not feel this is likely the main mechanism to explain the high therapeutic efficacy of acupuncture. A mechanism that they feel is more likely to explain the beneficial effect of acupuncture is related to visceral hypersensitivity.

Previous studies have shown that acupuncture decreases esophageal pain perception during intra-esophageal balloon distention, likely by decreasing mechano- and chemosensory sensitivity. By this mechanism, acupuncture may modulate visceral sensation in patients who failed PPI once daily, but the hypothesis needs to be verified by future studies.