Pregabalin Helpful for Functional Dyspepsia in Small Study

I Kotikula et al. AP&T 2021; 54: 1026-1032. Randomised clinical trial: the effects of pregabalin vs placebo on functional dyspepsia

Key findings (8 week, randomized placebo-controlled study)

  • The self-reported adequate relief rates in the pregabalin and placebo groups were 70.6% and 42.1% at week 4 (P = 0.02), and 70.6% and 44.7% at week 8 (P = 0.03), respectively
  • Pregabalin improved the overall quality of life (P = 0.03)
  • The most common adverse event with pregabalin was dizziness, occurring in 51.6% of patients

My take: In this study, pregabalin led to significant alleviation of dyspeptic symptoms, especially in patients with predominant epigastric pain.

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Does negative testing reassure patients?

Probably not according to a recent study (JAMA Intern Med, published online Feb 25, 2013, dpi:10.1001/jamainternmed.2013.2762).

In this study, the authors systematically reviewed the literature and, after screening 9742 studies, identified 14 randomized controlled trials (n=3828 patients) which met inclusion criteria, including the following:

  • Randomized control trial
  • Adult participants with symptoms indicating a low probability of serious disease

Studies were excluded if they were not published in a peer-reviewed journal or if they were undertaken in a tertiary care setting.  Eight trials involved diagnostic testing for dyspepsia (mainly endoscopy), three involved radiography for back pain, and the other three included testing for chest pain, headache and palpitations.  Long-term follow-up varied from 4 to 18 months.

Key Findings:

  • Patients’ illness concern (odds ratio 0.87 in three trials) and anxiety (standardized mean difference 0.06 [-0.16 to 0.28] in two trials) were not reduced in the short or long term.
  • No overall long-term effect on symptom persistence was noted (odds ratio 0.99)


  • The authors examined only reassurance for patients, not for physicians.
  • Participants were not blinded
  • Overall, small number of study participants

In the discussion, the authors note that observational studies “suggest that illness concerns reappear within hours of receiving a normal (negative) test  result.”

For pediatric gastroenterologists, the conclusions from this article add another wrinkle when deciding how much workup is indicated for conditions like recurrent abdominal pain.  Previous data indicate that maternal anxiety is the most consistent predictor of outcome for recurrent abdominal pain (Acta Paediatr 2007; 96: 697-701); this study does not address whether patient proxies are reassured by negative testing.  And, other studies have shown that patients rate their care higher after diagnostic testing (Don’t miss the gorilla! | gutsandgrowth).

As a fellow, I was told: “Don’t just do something, stand there” from Bill Balistreri; he also recommended avoiding the mentality of “Scope first, think second.” While this current study suggests that there is a lack of long-term benefit when testing is done primarily for reassurance, convincing families that their child does not need testing is often difficult.

Does buspirone help functional dyspepsia?

A recent randomized, double-blind, placebo-controlled crossover functional dyspepsia (FD) trial showed that 4 weeks of treatment with buspirone (10 mg TID) improved overall symptom severity, including early satiety and bloating (Clin Gastroenterol Hepatol 2012; 10: 1239-45).

This study enrolled 17 patients (13 women) with a mean age of 38.5 years.  There were two 2-week treatment periods and a 2-week washout in between.  Patients filled out a dyspepsia symptom score before treatment and at the conclusion.  In addition, patients underwent gastric emptying by using breath tests and barostat measurement.

Overall symptom score was improved with buspirone compared to placebo: 7.5 ± 1.3 vs. 11.5 ± 1.2.  Symptoms of postprandial fullness, early satiety, and abdominal bloating all improved significantly.

Buspirone treatment increased gastric accommodation compared with placebo: 229 ± 28 vs. 141 ± 32 mL respectively.  Overall, gastric emptying was not affected by buspirone treatment; however, delayed emptying of liquids was evident (half-life = 64 vs. 119 minutes respectively).

The effect of buspirone on FD appears to be primarily related to improvement in gastric accommodation.  Impaired accommodation has been identified in about 40% of FD patients.  Buspirone which is a 5-HT1A receptor agonist acts on cholinergic nerve endings and leads to relaxation of the proximal stomach.

Buspirone also is used for the treatment of anxiety.  In the present study, baseline anxiety scores were not correlated to symptom improvement but these scores were not followed at the end of treatment.

In this small study, buspirone was well tolerated and had similar adverse events as placebo.  In previous studies, it has been associated with light-headedness, dizziness, and nausea.

Given the small scale of the study, it would be premature to consider buspirone a proven treatment for FD; however, this study provides the framework for larger studies to determine more conclusively the role of buspirone for FD.

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HEROES trial

HEROES is definitely a catchy acronym (Arch Intern Med 2011; 171: 1929-36); HEROES is short for Helicobacter eradication relief of dyspeptic symptoms.

In pediatric practice, when Helicobacter pylori infection is identified, efforts are made to eradicate it.  However, studies have not been conclusive about whether this is beneficial for individuals with ‘functional dyspepsia.’  A 2006 Cochrane review of 21 trials found only 6 were positive for eradication.  Previous trials had not focused on primary care patients who may be more prone to respond.  As such, the investigators randomly assigned 404 patients (adults with average age of 46 years) into a group (n=201) treated with antibiotics and a control group (n=203); this was a randomized double-blind placebo-controlled clinical trial at a single center.  All eligible patients had to meet the Rome III criteria for functional dyspepsia and have H pylori infection.  Individuals with heartburn and irritable bowel were excluded. The antibiotic group received omeprazole, amoxicillin, and clarithromycin whereas the control group received omeprazole and placebo –both groups received treatment for 10 days.

In the antibiotic group, 49% achieved at least a 50% reduction in symptoms at 12 months; the control group had a 36.5% response.  Overall, 78.1% of the antibiotic cohort improved compared with 67.5% in the control cohort.

Although the findings of the study indicate improvement with a course of antibiotics, what to do with these results is not clear.  Worldwide, at least 50% of the population is infected by H pylori.  In addition, dyspeptic symptoms afflict up to 40% of the adult population in Western countries.  Due to the enormity of these problems, translating the results of this study into practical treatment strategies is difficult.

Additional references:

  • -JPGN 2011; 52: 387. Impact of Rome III criteria on yield. Still 2.8% w/o alarm symptoms that had significant endoscopic findings.
  • -Clin Gastro & Hep 2008; 6: 746. Antidepressant venlafaxine not effective in functional dyspepsia in double-blind, randomized, placebo-controlled study. n=160.
  • -Cochrane Database Syst Rev 2006; (2): CD002096. Rx of H pylori in functional dyspepsia.
  • -Gastroenterology 2007; 133: 799. Natural hx of functional disorders: 20% persist w same Sx, 40% develop other Sx, 40% get better. Large study from Olmstead county (n=1365)
  • -Gastroenterology 2007; 132: 1684.  Changes in cerebral blood flow during gastric balloon distention in dyspepsia.
  • -Gastroenterology 2006; 130: 1466-79. Functional gastroduodenal d/o. Acid suppression is 1st line Rx.
  • -Gastroenterology 2005; 129:1753-55, 1756-80, 1711. Mgt & guidelines for dyspepsia. In pts < 55 w/o alarm sx, test for H pylori and rx c PPI. In pts who don’t respond, consider EGD. Other Rx unclear: prokinetics, anticholinergics, antidepressants.
  • -Gastroenterology 2004; 127; 1239. Review of functional dyspepsia. Rx initial c acid-blocker/prokinetic reasonable, if not helpful, consider tricyclic, or clonidine. Eliminate H pylori. Sumatriptan may help
  • -J Pediatr 2005; 146: 448, 500.  Dyspepsia in children often associated with delayed GE and reduced gastric volumes
  • -Gastroenterology 2003; 125: 1219-26. Algorithm suggested:1. chech pylori 2. Rx c PPI/H2RA.  3. If persists, EGD.  If EGD neg, consider elavil
  • -Clinical Gastro & Hepatology 2003; 1: 356. Increased Mast cells noted.
  • -Gastroenterology 2002; 123: 1778, 2132. Use of hypnosis for NUD.
  • -Ann Intern Med 2001; 134: 361-369. Meta-analysis of H pylori & NUD. Non-significant/minor improvement c eradication.