Functional heartburn: An underrecognized cause of PPI-refractory symptoms

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Patient education is key

Patient education about the pathogenesis, natural history, and treatment options is the most important aspect of treating any functional gastrointestinal disorder. This includes the “brain-gut connection” and potential mechanisms of dysregulation. Patient education along with assessment of symptoms should be part of every visit, especially before discussing treatment options.

Patients whose condition is diagnosed as functional heartburn need reassurance that the condition is benign and, in particular, that the risk of progression to esophageal adenocarcinoma is minimal in the absence of Barrett esophagus.13 Also important to point out is that the disorder may spontaneously resolve: resolution rates of up to 40% have been reported for other functional gastrointestinal disorders.14

Antisecretory medications may work for some

A PPI or H2-receptor antagonist is the most common first-line treatment for heartburn symptoms. Although most patients with functional heartburn experience no improvement in symptoms with an antisecretory agent, a small number report some relief, which suggests that acid-suppression therapy may have an indirect impact on pain modulation in the esophagus.15 In patients who report symptom relief with an antisecretory agent, we suggest continuing the medication tapered to the lowest effective dose, with repeated reassurance that the medication can be discontinued safely at any time.

Antireflux surgery should be avoided

Antireflux surgery should be avoided in patients with normal pH testing and no objective finding of reflux, as this is associated with worse subjective outcomes than in patients with abnormal pH test results.16


Table 2. Neuromodulators to treat functional esophageal disorders
No drug has yet been approved by the US Food and Drug Administration to treat functional heartburn, and clinical evidence for treating this condition is minimal. Using neuromodulators to reduce pain perception is the mainstay of treatment for functional gastrointestinal disorders, including functional heartburn. Table 2 lists neuromodulators used to treat functional esophageal disorders, with recommended dosing intervals.

It is important to discuss with patients the concept of neuromodulation, including the fact that antidepressants are often used because of their effects on serotonin and norepinephrine, which decrease visceral hypersensitivity.

The selective serotonin reuptake inhibitor citalopram has been shown to reduce esophageal hypersensitivity,17 and a tricyclic antidepressant has been shown to improve quality of life.18 These results have led experts to recommend a trial of a low dose of either type of medication.19 The dose of tricyclic antidepressant often needs to be increased sequentially every 2 to 4 weeks.

Interestingly, melatonin 6 mg at bedtime has also shown efficacy for functional heartburn, potentially due to its antinociceptive properties.20

Alternative and complementary therapies

Many esophageal centers use cognitive behavioral therapy and hypnotherapy as first-line treatment for functional esophageal disorders. Here again, it is important for the patient to understand the rationale of therapy for functional gastrointestinal disorders, given the stigma in the general population regarding psychotherapy.

Cognitive behavioral therapy has been used for functional gastrointestinal disorders for many years, as it has been shown to modulate visceral perception.21 Although published studies are limited, research regarding other functional esophageal disorders suggests that patients who commit to long-term behavioral therapy have had a significant improvement in symptoms.22

The goal of esophageal-directed behavioral therapy is to promote focused relaxation using deep breathing techniques, which can help patients manage esophageal hypervigilance, especially if symptoms continue despite neuromodulator therapy. Specifically, hypnotherapy has been shown to modulate functional chest pain through the visceral sensory pathway and also to suppress gastric acid secretion.21,23 A study of a 7-week hypnotherapy program reported significant benefits in heartburn relief and improved quality of life in patients with functional heartburn.24 The data support the use of behavioral therapies as first-line therapy or as adjunctive therapy for patients already taking a neuromodulator.


During a follow-up visit, the patient is given several printed resources, including the Rome Foundation article on functional heartburn.5 We again emphasize the benign nature of functional heartburn, noting the minimal risk of progression to esophageal adenocarcinoma, as she had no evidence of Barrett esophagus on endoscopy. And we discuss the natural course of functional heartburn, including the spontaneous resolution rate of about 40%.

For treatment, we present her the rationale for using neuromodulators and reassure her that these medications are for treatment of visceral hypersensitivity, not for anxiety or depression. After the discussion, the patient opts to start amitriptyline therapy at 10 mg every night at bedtime, increasing the dose by 10 mg every 2 weeks until symptoms improve, up to 75–100 mg every day.

After 3 months, the patient reports a 90% improvement in symptoms while on amitriptyline 30 mg every night. She is also able to taper her antisecretory medications once symptoms are controlled. We plan to continue amitriptyline at the current dose for 6 to 12 months, then discuss a slow taper to see if her symptoms spontaneously resolve.

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Beyond depression: Other uses for tricyclic antidepressants

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